1. A 67-year-old CKD 5 patient due to MPGN nephropathy received an offer from his 51-year-old living donor (family friend). She is on the waiting list for 8 years (highly sensitised with cRF (cPRA) of 97% due to pregnancy and blood transfusion. Her crossmatch results are shown below. Please answer the following:
- Comment on the report?
- What do you think about the DR mismatch shown in this report?
- Explain the defaulting in HLA A locus
- Would you accept the offer?
- If yes, how would you manage his immunosuppression?
- If no, what are the other options?
Dear all, Check these
https://www.aacc.org/-/media/Files/Transcripts/Pearls-of-Laboratory- Medicine/2018/Slides/HLA-Basic-Terminology-and-Nomenclature-Tumer-Slides.pdf?la=en&hash=9844046EF5BF67763B67E7ABD060600C11620DCE
These delineate the HLA basics and the importance of broad and split typing
Dear Dr Ala this link is not working can you kindly upload again Regards
https://www.aacc.org/-/media/Files/Transcripts/Pearls-of-Laboratory-Medicine/2018/Slides/HLA-Basic-Terminology-and-Nomenclature-Tumer-Slides.pdf?la=en&hash=9844046EF5BF67763B67E7ABD060600C11620DCE
Thanks Murad
thank you
Dear All
None of you got the match right
there is split at HLA A locus, default at HLA A locus and another split at HLA DR locus
Dear all:
As we concluded 2 days ago in rely to Sherif Yusuf that this issue is due to non DSA antibodies as the Recipient has antibodies
To which the donor has no corresponding antigen.
Probably due to some previous sensitisation process.
NOW as practicing TRANSPLANT NEPHROLOGISTS you need to answer the following:
1.What is the impact of these antibodies are they a benign issue?
Non-DSA or third-party antibodies are antibodies that develop to HLA antigens that are not donor-specific.
Non-DSA can develop due to sensitization to HLA antigens either from previous blood transfusions, pregnancy, or previous transplant.
Sensitization can affect transplantation either before or after transplantation
Highly sensitized transplant recipients are extremely difficult to find a suitable donor with a negative crossmatch (1), and this may affect the plan by accepting relatively incompatible donor kidneys which will be better than putting the patient for a long time on the waiting list, and some recommend desensitization (although its effect is debatable) to remove these HLA antibodies and increase the chance of transplantation.
Increased sensitization as measured by PRA is correlated with graft survival, one study found that 10 years graft survival of 44% in highly sensitized transplant recipients with PRA ≥98 percent compared to 52% in non sensitized patients. (2)
Detection of DSA is well-known risk factor for reduced graft survival and is associated with a 10-fold increase in the risk of graft loss as it is associated with ABMR which is the commonest cause of graft loss . (3)
The significance of third party non DSA on graft survival is not clear, a study addressing the relation between PRA and graft survival in 4000 transplant recipients who received HLA identical grafts from siblings found that 10 years’ graft survival was 72% in patients with 0 PRA, 63% in patients with PRA between 1-50% and 56% in patients with PRA > 50% (4)
Moreover, the presence of HLA antibodies including the third party was found to increase the risk of DGF and the risk of death-censored graft loss increased markedly in patients with DGF if HLA antibodies are present pre-transplantation including non-DSA (5)
On the other hand, one study found no correlation between pre-transplant PRA due to non DSA HLA antibodies and graft survival (6) and another study found that only DSA (and not third party HLA ) has significant impact of the incidence of DGF (7)
So … transplanting patients with high cPRA even if there is no DSA may be difficult as there is a low probability to find a suitable donor and associated with a higher probability of ABMR, DGF and subsequently reduced graft survival thus they should be considered as high-risk transplantation and may indicate aggressive immunosuppression with desensitization (which is not my opinion) may provide an option in order to find a suitable donor
REFERANCES
Thankyou sherif for your logic report so one can conclude:
1.If they are present alone eluting them alone is controversial.
2 As in the case above who is highly sensitized and you decide to proceed they will be dealt with among other antibodies during PE and strong IS.
Well done
9
http://hla.alleles.org/antigens/broads_splits.html
DR13, DR14 are splits of DR6
HLA 31, HLA 32 are splits of HLA-19
Comment on the report?
ABO compatible donor and recipient
HLA 120 ( broad) 121 (split)
Non DSA antibodies with high MFI
Positive T and B cells cross match by FCXM
But negative autocrossmatch
What do you think about the DR mismatch shown in this report?
There is one mismatch by split technique
Would you accept the offer?
Yes I will accept this offer because the patient is highly sensitised with cPRA of 97% she is on waiting list for long time
But she should be aware about early antibody mediated rejection
If yes, how would you manage his
immunosuppression?
Induction by ATG with triple immunosuppressive medication as maintenance (Tac,MMF and predinsilone)
If no, what are the other options?
Paired exchange
Deceased donor
1) Comment on the report?
ABO compatible.
HLA split at A and DR locus.
HLA default A locus.
FXCM high.
Positive DSA with high MFI.
Conclusion : High immunological risk
2) What do you think about the DR mismatch shown in this report?
DR split mismatch. Indicate poor graft outcome.
3)Explain the defaulting in HLA A locus
HLA A 80 is a rare antigen which defaulted to A1
4)Would you accept the offer?
Yes but after counseling patient the relative high risk of allograft rejection and possible complications following intensified desensitization protocol.
5)If yes, how would you manage his immunosuppression?
Desensitization with cycle of plasmapheresis and IV IG.
Induction : ATG.
Maintenance : Tacrolimus, MMF , Prednisolone.
Regular monitoring DSA and protocol allograft biopsy if evidence of rejection.
6)If no, what are the other options?
Kidney pair exchange program.
Deceased kidney donor program.
· Comment on the report?Both donor and recipient are sharing same blood so there are ABO compatible , high risk patient with positive cross match and presence of non DSA with significant MFI .high risk of recurrence of MPGN .
· Broad 120 ,Default 020 ,Split 121
· What do you think about the DR mismatch shown in this report? DR 13 and DR 14 are split from DR 6
· Explain the defaulting in HLA A locus :It is rare antigen { HLA 80 } to HLA A1
· Would you accept the offer?I Would accept this offer if he has not possible donor and because he is waiting for 8 years without being transplanted .
· If yes, how would you manage his immunosuppression?Desensitization with IVIG PLASMA EXCHAGE and Rituximab .Induction by ATg maintenance by {TAC, PREDNISLONE and MMF }
· If no, what are the other options?Look for pair exchange or waiting list of diseased donor
Comment on report
DR mismatch
HLA A loc
Offer acceptance
Management of immunosuppression
Other options
High immunological risk, positive FCXM wet cross match presence of DSAs(class 1 and 2),high recurrence rate of original kidney disease(MPGN)
o ABO compatibility: blood group AB(compatible),RH is not important in solid organ transplantation
o HLA typing:
HLA A80 is a rare antigen defaulted to HLA-A1.
A31,A32 are splits for the broad antigen A19. DR13,DR14 are splits for DR6.
Broad: 1,2,0
Splits:1,2,1
Dafault:0,2,0
o Highly sensitized patient(cPRA 97%), primary disease MPGN(high recurrence rate), DSAs against both class 1 and class 2 (RIS 2)
o Positive current wet FCXM against both B and T cells and negative auto cross match
No DR mismatches at the broad level and 1 mismatch at split level.
The HLA-A80 is a rare antigen, So, it is defaulted to HLA-A1
I would accept the offer because this is a highly sensitized patient and he is on the waiting list for 8 years. However, this patient requires desensitization with Plasmapheresis , IVIG with/without Rituximab to achieve a negative cross match result.
Induction with a depleting agent (r ATG/Alemtuzumab) then maintenance with Tacrolimus(keep high rough level) , MMF and steroids.
Regular follow up of renal functions, proteinuria, frequent monitoring for DSAs and protocol biopsy
Enroll in Paired kidney exchange program or Wait for more suitable living or deceased donor
ABO: Donor AB +VE, Recipient AB -VE (Compatible as Rh is not associated with solid organ Tx).
HLA mismatch:
HLA A19 (Broad)——> HLA A31, HLA A32 (Split)
HLA A80 rare antigen that is defaulted to HLA A1
HLA DR6 (Broad)——>HLA DR13, HLA DR14 (Split)
Broad antigen level: MM 120,
Default antigen level: MM 020
Split antigen level: 121
DSA: recipient has DSA against HLA B51 with MFI>4000, and against HLA DR4 with MFI> 3000 which are of high clinical significance.
Crossmatch: FCMX was positive for T and B (DSA against class I) , auto cross match was negative.
HLA DR6 (Broad)——> HLA DR13, HLA DR14 (Split)
By Broad antigens-> there is no mismatch in DR
By split antigens-> there is one mismatch.
HLA DR mismatch has higher adverse impact on graft outcome than HLA A and HLA B mismatches.
HLA A80 is a rare antigen that is defaulted to HLA A1
Highly sensitized patient with PRA:97%, original kidney disease MPGN with high rate of recurrence post-transplant (10-40%), has positive cross match with high DSA. All of the above make me reluctant to accept this offer.
However, other clinician might accept the offer because of long waiting time for almost 8 years.
Desensitization: Plasma exchange, IVIG, rituximab aiming for negative crossmatch..
High risk induction immunosuppression: ATG
Augement maintenance immunosuppression: Tacrolimus/MMF/steroids
Regular follow up of graft function and monitor DSAs.
Either 1- Paired kidney exchange scheme
2-Wait for more suitable donor either Deceased or another living donor.
-Regarding blood group: ABO compatible (RH is not related to solid organ transplantation as it is only expressed on RBC).
-regarding tissue typing: HLA A31,32 are split antigens for HLA-A19 and HLA DR13,14 are split antigens for DR6.also A80 is a rare antigen so it can be defaulting to A1
Accordingly, Mismatch will be 020 (on broad level) and 121 on the level of split antigen, patient has HLAB 51 antibodies which is DSA (donor B51) with MFI 4451 which is significant, FCMX was positive for T & B (explained as DSA is against class I) with negative autoantibodies.
HLA DR13,14 are split antigens for DR6 so, with zero mismatches on broad Antigen and 1 mismatch on a split level.
HLA A80 is a rare antigen and defaulted to HLAA1
If it’s possible to do a CDC DTT crossmatch first if it was positive, I will not accept the donor and I will enroll her into paired kidney donation program. If negative I will accept the donor and I will proceed for desensitization until negative FCXM using 3-5 sessions of plasma exchange followed by 2gm IVIG then rituximab 500mg after 1w to avoid neural fac fragment saturation after IVIG.
1-Desensitization protocol desensitization until negative FCXM using 3-5 sessions of plasma exchange followed by 2gm IVIG then rituximab 500mg after 1w to avoid neural fac fragment saturation after IVIG.
2-Induction with ATG 3mg/kg total dose.
Maintenance immunosuppressive (Tacrolimus, MMF & steroid ), DSA frequent monitoring.
to be enrolled in a paired kidney exchange program
This pair is ABO compatible ,, Mismatch on level of broad 021 & 121 on level of split antigen , patient has DSA , HLAB 51 with MFI 4451 which is significant DSA , & FCMX was positive for T & B & negative autoantibodies .
Zero mismatch on broad Antigen & 1 mismatch on split one , No DSA( as HLA DR4 is not DSA) , split antigen carry risk of poor graft outcome after TX .
HLA A80 is a rare antigen which is defaulted to HLAA1.
Quite challenging case as , patient has CKD 5 due to MPGN ( high rate of recurrence ) on waiting list for 8 years due to highly sensitized patient cPRA 97% , patient has DSA against HLAB51 with MFI 4451 & positive cross matching against T & B , I will ask for CDC if it is positive , will not proceed for transplant , if negative , look for channel shift value if less than 250 , will proceed with desensitization protocol after counselling the patient pros& cons of the transplant & explain the high risk of recurrence of the primary disease & AMR post-transplant .
1-Desensitization protocol ( rituximab, IVIG & plasmapheresis pre transplant , followed by IVIG & plasmapheresis sessions post-transplant.
2-Induction with ATG or alemtuzumab
Maintenance immunosuppressive (Tacrolimus , MMF & steroid ) , protocol kidney biopsy & DSA .
This patient has limited options as she was highly sensitized with cPRA 97% , so it is difficult to get cadaveric offer , the other options , searching for other living donor ,paired exchange program or staying on the waiting list & eventually will go for dialysis .
* ABO is compatible AB
* HLA match
●Broad : 020
As HLA A 80 is a rare antigen defaulted to A01
HLA A31 and HLA A32 are Broad antigens for HLA A19
HLA DR13 and HLA DR14 Split antigens of HLA DR6
●Split HLA mismatch : 121
*Cross match :
Current cross match is positive for both B and T cells
*DSA screen
Donor specific antibody with MFI 4451 for HLA B51.
Non-DSA against HLA-DRA with MFI 3215
high immunological risk with positive cross match and presence of DSA.
DR mismatch :
DR13 and DR14 are splits for DR6. there is 0 mismatch of DR on broad matching while there is 1 mismatch on spilt HLA matching.
The HLA A80 is a rare antigen, defaulted to HLA A1
patient is a highly sensitized patient (cPRA 97%)with a positive T and B cell FCXM and presence of DSA with MFI 4451.
the patient will require desensitization with Plasmapheresis and IVIG and rituximab to achieve a negative crossmatch before proceeding with the transplant.
Also the patient will require induction immunosuppression and tacrolimus based triple drug maintenance immunosuppression .
1) Induction therapy: Injection Anti Thymocyte Globulin (ATG) in dose of 1-1.5 mg/kg per day for 4-6 days (total dose 6 mg/kg).
2) Maintenance immunosuppression: Triple drug therapy including
a. Tacrolimus: Target trough level of 8-10 ng/ml
b. Mycophenolate mofetil (MMF): 1000 mg twice a day
c. Corticosteroids: methylprednisolone 500 mg IV on the day of surgery, followed by prednisolone 1mg/kg/day for 3 days and then 20 mg/day, to be tapered to 5 mg/day over next 6 to 8 weeks.
If no , searching for new donor or Donor Exchange program .
Comment on the report:
ABO compatible renal transplant is being planned for this recipient and donor…
HLA typing of the donor and the recipient:
Broad Mismatch : 0 2 0 mismatch
Split Mismatch : 2 2 1 mismatch
This is due to the following : HLA A 31 and HLA A 32 are a split of HLA 19…HLA DR13 and 14 are split of HLA DR 6
HLA A 80 is a rare antigen and it is to be defaulted to the nearest HLA A 01..so the defaulted HLA is typing mismatch is 121
Cross matching results:
This patient is a highly sensitized due to previous Blood transfusion and pregnancy…the latest flow cytometry cross match is positive for T cell and B cell…The auto cross match is negative for both T and B cells…
The DSA is positive for HLA B51 with MFI of 4451…This is directed against the donor at the split level and the broad level and is highly significant and it is donor specific….I would consider this as a cause of concern and may pose risk of antibody mediated rejection in the immediate post operative period….The DSA against HLA DR4 with MFI of 3215 is not specific for the donor at the split level, so this becomes a third party DSA….
Considering the high cPRA score, the chance of the patient getting a deceased donor kidney in the program would be low…We could proceed with this case after desensitiization with IV Rituximab 2 doses of 375mg/m2, Plasmaphresis and IVIG, triple immunosuppression 2 weeks before transplant…I would repeat CDC,FCXM cross match before the transplant and proceed if CDC is negative and T cell Cross match is negative or low MCS positivity <100…WE need to use Inj ATG as induction agent and maintain the patient of standard triple immunosuppression protocol with Tacrolimus level between 7- 10 mg/ml….I would inform the patient about the risk of AMR in the future due to high sensitization…Patient needs close monitoring after renal transplant in terms of monitoring for DSA and protocol biopsies also
* paired kidney exchange donation programme.
– yes, I will accept the offer but with the following plan:
* desensitizations with plasmapheresis , IVIG and Rituximab .
* induction therapy with ATG vs Alemtuzumab.
* maintainance immunesuppression with prednisolone,tacrolimus and MMF.
* follow up tacrolimus level with target (8-10) ng/ml ,monitor DSA and protocol biopsy
* put in mind the primary disease is MPGN carry high risk for recurrence follow up closely with kidney functions proteinura.
HLA-A 80 is a rare antigen which is default to HLA-A1
-O mismatch when using broad antigen and 1 mismatch when using split antigen .
– the initial collaborative transplant study analysis the major impact on kidney outcome come from mismatches from HLA-DR and HLA-A antigens with little effects from HLA-A.
– Alleic variants of HLA-DR B1 are linked with either none DRB3. or one of gene DRB3 DRB4 DRB5 within DR molecules the B chain contain all the polymorphism.
– the recipient and the donor in the attached report are ABO compatible.
– Rh has no role in kidney transplantation.
-HLA mismatch by broad is 020 as HLA-080 is default to HLA A01 and both HLA A31,32 are split antigens for HLA-A19 and. HLA DRB1 13, 14 are split antigens for HLA DRB6.
– so split mismatch is 121.
-If we default for broad it will be 120.
* this patient carry high immunological risk and high risk of recurrence of primary diseases.
FCXM showed positive for T cell and B cell- antibody against HLA class 1 or
both HLA class 1and 2.
DSA against HLA51 and HLA DR4
_ Compatible ABO is compatible. Rh matching is not needed because it is not presented on the allograft cells.
_ HLA-A80 is a rare antigen and it is defaulted to HLA A1. HLA- A32 and A31 both are split of A19. HLA- DRB13 and DRB14 are split of DRB6, so ,broad matching is 1:2:0 and with default is 0:2:0. Split matching is 2:2:1 and with default is 1:2:1. – HLA DR is the most important regarding graft function and survival.
_Positive T and B FXCM, negative auto -cross match ..
_Highly sensitized patient with c PRA 97%,positive DSA form B51 with MFI 4451 (>2500) and negative for DR4 with MFI = 3215 (<5000).
_ More than 8 years in waiting list.
Would you accept the offer?
Positive T and B FXCM, in addition to the presence of DSA and high CPRA (97%) make this high risk transplantation; better to defer.
If yes, how would you manage his immunosuppression?
Patient discussion
Desensitization :Plasmapheresis and IVIG. If DSA levels continued to be high with positive cross match, Rituximab to be added. Induction IS with Alemtuzumab and methylprednisolone. Maintenance Immunosuppression with Tac (with high trough level in the first three months), MMF and Prednisone. Close monitoring of DSA level by SAB and protocol biopsy.
If no, PKD program.
o ABO compatible couple (even matched), while Rh group is not considered in renal transplant.
o As regard HLA typing:
§ It is presented in split antigens.
§ Mismatch on level of split antigens is 1,2,1.
§ While taking into consideration that:
a) HLA A 31, 32 are split Ag of HLA A 19.
b) HLA DR B 13, 14 are split Ag of HLA-DR 6.
c) HLA A80 is rare Ag (defaulted to HLA A 1.
§ so on level of broad Ag- the mismatch will be 020 on levels on HLA (A, B and DR respectively).
o As regard cross match, now he has positive both B and T cell cross match that indicates that he has anti HLA class 1 antibodies.
o As regard positive DSA:
§ Anti HLA B 51 as long as more than 2000 MFI (significant) and mismatch on level on HLA b is 2, so they are DSA.
§ However, anti HLA DR4 is less than 5000, and no mismatch on the level of broad antigens, they are non DSA or 3 rd party antibodies because The recepient has no Donors HLA antigens, therefor antibodies against DR4 are non DSA against third party. Its essentially due to shared epitop between patients DR14 and DR4 antigens.
.
§ So he is highly sensitized recipient.
· It is zero at level of broad Ag.
· 1 at level of split Ag.
· Presence of antibodies is non-DSA.
· However, split Ag variation can still carry risk of poor graft function after transplant (DGF) and worse graft outcome on long term outcome.
I will accept the transplant but with:
· Desensitization protocol with PEX, IVIG and rituximab.
· Strong induction with ATG and pulse steroids.
· Strong maintenance protocol (triple tacrolimus, prednisolone and MMF).
· Close monitoring of DSA and surveillance protocol biopsy to early detect AR and mange appropriately.
· In addition, taking into consideration, the original kidney disease of MPGN (with very high rate of recurrence), so close monitor of creatinine and A/C ratio to detect early recurrence.
Q5. Alternatives:
· Paired kidney exchange donation.
Comment on the report?
HLA A 80 is rare antigen will be known as A1
HLA A 31 and 32 are split of A19
HLA B 39 is split of 16
HLA B 51 is split of B5
HLA 13 and 14 are plit of DR6
Broad: 020
Split:121
Default Broad:120
Default Split:221
FCXM showed positive for T cell and B cell- antibody against HLA 1 or both HLA 1 & 2
DSA against HLA51 and HLA DR4
DSA against HLA DR4 is third party DSA as recipient has no DR4 antigen
Would you accept the offer?
If yes, how would you manage his immunosuppression?
This will be highly sensitized transplant (cPRA 97% and DSA)
I would start with desensitization with PLEX and IVIG with or without Rituximab and induction agent will be Thymoglobulin and maintain with MMF,Tac and prednisolone. I would monitor DSA post transplant
If no, what are the other options?
Paired kidney exchange program
Here, we have :
– ABO compatible and RH diference is not signicant
– HLA Typing :
Broad : 1-2-0 -because HLA A : A 32 and A 31 are split antigen from broad A19
Split: 2-2-1
P.S.: attention is drawn to the rare antigen A 80
– Crossmatch results:
There was a technical error occurring in T-FCXM positive with B-FCXM negative which was fixed in 2020. So, with both positive we have DSAs to HLA class I or mixture of DSAs to class HLA I and II
– DSA screening:
Recipient has DSA against HLA DR4 with MFI 3215 with low significance because it is below the cut-off point
But, DSA against HLA B51 with MFI 4451 which is close to the cut-off point (5000) becoming important in risk assessment
In the HLA DR there was the presence of splits DR 13 and DR 14 that belong to the same broad DR 19
Thres is a rare antigen A 80
I would not accept the offer because in addition to the patient being highly sensitized, we also had a high incompatibility of HLA Typing and the identification of DSAs.
Would opt for desensitization with plasmapheresis followed by IVIg and humanized monoclonal antibody
●Comment on the report?
*ABO :The donor and recipient are ABO Compatible with blood group AB ,
The difference in RH is not significant in transplantation.
* HLA mismatch
-On Broad antigen level :0-2-0
As A31 and A32 are split antigen from the broad one A19.
A80 is considered to be a rare Antigen .
Also DR 13 and DR 14 are splits of the broad antigen DR 6.
– mismatch at split antigens level is 1-2-1
•Crossmatch:
The last FCXM is positive for both T and B cell so there is antibodies to both HLAclass-I and class-II.
•DSA screening:
Recipient has DSA against HLA B51 with MFI 4451 which is high and significant.
Also there is DSA against HLA DR4
But its not donor-specific.
●What do you think about the DR mismatch shown in this report?
DR 13 and DR 14 are split antigens of broad antigen DR 6 so no mismatch on broad level .
HLA-DR 5 showes one mismatch .
Mismatch of HLA DR was found to be associated with poor graft survival.
●Explain the defaulting in HLA A locus?
HLA-A80 is a rare antigen so recipient how has this antigen are considered to have the nearst Ag HLA- A1
●Would you accept the offer? ●how would you manage his immunosuppression?
The patient is highly sensitized with high MFI against DSA
So i prefer to look for another more matched doner or paired kidney exchange .
If not available we will do desensitization with
Plasma Exchange + IVIG + Rituximab until crossmatch becomes negative then induction with ATG AND Maintenance on triple immunosuppression( MMF + prednisolone + Tac).
Follow up of DSA 1,3,6,and 12 months posttransplantation.
●what are the other options?
Paired kidney exchange program
1.ABO compatible
Broad HLA mismatch-0:2:0
Split HLA mismatch-1:2:1
FCXM positive for both T and B cell.
2.DR mismatch will produce denovo Ab which
will decrease graft survival.
3.HLA A80 is a rare Ag which defaulted to HLA
A1.
4.Yes i ll accept tx if CDC XM is negative.
5.I ll do tx with desensitization with plasma
exchange and ivig and induce with ATG and
Maintainance triple immunosuppression and
Close monitoring of dsa.
6.if no tx,then go for paired exchange and
continue hd.
ABO compatible donor & recipient
Tissue matching shows: Broad 020, split 221( HLA19 split into HLA 31 & 32, HLA DR6 split into DR13 & 14) & default 120
FCXM was positive only for auto antibodies (Cells), but subsequent cross match became positive for T cells ( negative auto antibodies). Last crossmatch was positive for both T & B cells with positive DSA against HLA class I & II in addition to high PRA ( recipient highly sensitized).
Because DR4 antigen is not available so antibodies against DR4 are more likely to be non DSA.Also DR antigen had split (DR13 & DR14 are split from DR6) which had high risk of rejection & associated with poor graft survival.
HLA A80 is the least common antigen & almost exclusively found among African patients so it defaulted to HLA-A1.
This patient is highly sensitized with high HLA mismatch with his donor, but because of long vintage of hemodialysis & high PRA his chance to have more compatible donor is difficult. So if the recipient accept the risk of this donor, yes I will precede for transplantation with desensitization ( PP+ IVIG & rituximab), induction with T cell depleting agent & maintained on triple ( CNI, MMF & steroid) immunosuppressants, with close monitoring of DSA.
If the patient didn’t accept this donor, he can be enrolled in paired exchange program.
This cross-match report is ABO compatible, although there is Rh difference, it is not clinically relevant to histocompatibility barrier.
There are 111 split mismatches and 120 broad mismatches.
The A32 and A31 are splits of A19.
B39 is split of the B16 and B51 is split of B5.
DR13 and DR14 are split of DR6.
The allele of DR4 is DRB1 and it is in DR 53 public epitope.
This cross-match demonstrates mismatches in the splits of DR6 at the DRB1 region, not DR4 mismatch. DR4 mismatch in this case is at the DRB5 region. As a result, the anti HLA DR4 antibody in this case is a non-DSA antibody and should not be considered as a risk factor for rejection.
(All HLA DR types have the DRB1 gene and some contain additional DRB genes, DRB3, DRB4, and DRB5, which form a second cell surface heterodimer.
HLA DR mismatch is an independent risk factor for de novo DSA formation and T cell mediated rejection, especially in elderly kidney transplant recipients. Two mismatched at HLA DR indicate high immunologic risk in kidney transplantation. thus, it is recommended using induction therapy with lymphocyte depleting agents such as ATG.)
HLA A1 and HLA 80 are in the same cross reactive group CREG: A1c
Thus, they consider the same broad antigens: 020 broad mismatch.
It depends on the possibility and accessibility of Kidney paired donation (KPD).
The recipient is highly sensitized and this transplantation with multiple HLA mismatch and high level of DSA against HLA B51 is correlated with poor graft survival and need for desensitization. (Although a different cut off level for MFI has been reported in different laboratories. For class I, MFI more than 2000, and for class 2, MFI more than 5000 can be considered).
If KPD is not possible or long waiting time for KPD, I will accept this donation and I will use the desensitization protocol before kidney transplantation (combination of IVIG, plasmapheresis, and Rituximab). I will prescribe lymphocyte depleting antibodies (Thymoglobulin or Alemtuzumab) and pulse of methyl prednisolone as an induction therapy and tacrolimus, MMF, and prednisolone for maintenance therapy.
Joining to the KPD program to find the best donor is another option.
· Q1. The provided report shows:
o ABO compatible couple (even matched), while Rh group is not considered in renal transplant.
o As regard HLA typing:
§ It is presented in split antigens.
§ Mismatch on level of split antigens is 1,2,1.
§ While taking into consideration that:
a) HLA A 31, 32 are split Ag of HLA A 19.
b) HLA DR B 13, 14 are split Ag of HLA-DR 6.
c) HLA A80 is rare Ag (defaulted to HLA A 1.
§ so on level of broad Ag- the mismatch will be 020 on levels on HLA (A, B and DR respectively).
o As regard cross match, now he has positive both B and T cell cross match that indicates that he has anti HLA class 1 antibodies.
o As regard positive DSA:
§ Anti HLA B 51 as long as more than 2000 MFI (significant) and mismatch on level on HLA b is 2, so they are DSA.
§ However, anti HLA DR4 is less than 5000, and no mismatch on the level of broad antigens, so they are non DSA or 3 rd party antibodies.
§ So he is highly sensitized recipient.
Q2. about DR mismatch:
· It is zero at level of broad Ag.
· 1 at level of split Ag.
· Presence of antibodies mostly non-DSA.
· However, split Ag variation can still carry risk of poor graft function after transplant (DGF) and worse graft outcome on long term outcome.
Q3. Default HLA A?
· HLA A 80 is a rare antigen, which is defaulted to the nearest Ag (to allow transplantation of recipients who have those rare Ag.
· So it is defaulted to HLA A1.
Q4. I will accept the transplant but with:
· Desensitization protocol with PEX, IVIG and rituximab.
· Strong induction with ATG and pulse steroids.
· Strong maintenance protocol (triple tacrolimus, prednisolone and MMF).
· Close monitoring of DSA and surveillance protocol biopsy to early detect AR and mange appropriately.
· In addition, taking into consideration , the original kidney disease of MPGN (with very high rate of recurrence), so close monitor of creatinine and A/C ratio to detect early recurrence.
Q5. Alternatives:
· Paired kidney exchange donation.
Comment on the report?
What do you think about the DR mismatch shown in this report?
Explain the defaulting in HLA A locus
Would you accept the offer?
If yes, how would you manage his immunosuppression?
If no, what are the other options?
Broad without defaulting will be 020
Broad with defaulting will be 120
Split 121 with the fault and 221 after default
DR13 and 14 are splits of DR6 so it’s acceptable
A80 is a rare Ag and can be defaulted to A1
I would accept this offer if there is no chance of a paired exchange programme but would require desensitization with Plex and Rituximab
Induction with ATG and triple immunosupression with follow up DSA levels
Comment on the report?
Donor-recipient pair is ABO compatable
Broad HLA mismatch 0.2.0
Split HLA mismatch 1.2.1
HLA A80 is a rare Ags
It’s defaulted.
New positive crossmatching to both T cells and B cells
Mean presence of antibodies to class I and class II HLA antigens.
FCXM auto is positive for T cells
DSA against HLA B51 with MFI 4451 (high ) donor-specific
DSA against HLA DR4 not donor-specific
What do you think about the DR mismatch shown in this report?
DR 13 and DR 14 are splits of DR 6
Explain the defaulting in HLA A locus:
HLA A80 is a rare Ags so it’s defaulted to A01
Would you accept the offer?
As the survival rate for her will be better if she do transplantation even with this high risk, than if she stay on hemodialysis, so I will accept this offer.
If yes, how would you manage his immunosuppression?
Desensitization by PLEX , IVIG , and Retuximab
Induction by ATG and high dose methylprednisolone
Maintenance by triple IS
Close follow up by RFT, protocol biopsy and DSA monitoring.
If no, what are the other options?
Either wait for more compatable donor or engagement with the paired kidney donor program.
* Comment on the report?
Patient highly sensitised because previous exposure to pregnancy and blood transfusion
patient has ABO computable and she has cPRA 97%
flocytometry strong positive for T cell
circulating DSA for HLA B5 & HLA DR 4 high.
* Explain the defaulting in HLA A locus?
there’s matching of HLA loci , HLA 32, 31 splits are broad of HLA A 19
split of 80 are rare antigen.
* What do you think about the DR mismatch shown in this report?
HLA DR 13, 14 are spilts of broad DR6.
* Would you accept the offer?
This offer can accepted for transplant
* If yes, how would you manage his immunosuppression?
patient need high sensitised anti rejection protocol
induction with Iv ATG and pulse therapy of steroid and plasma exchange to remove DSA
Maintenance therapy are low dose steroid and MMF and Tacrolimus
* If no, what are the other options?
if this not offer for transplant:
Looking for another compatible donor or Donor paired exchange program.
The donor and recipient are ABO compatible, here the RH positivity is not important as this is not presented in kidney tissue
we have 221 mismatch at the broad level while 120 mismatch the split level
DR13, DR14 are splits of DR6
HLA 31, HLA 32 are splits of HLA-19
historically the FCXM of B is negative but in the last test we have both B& T FCMXM which is mainly due to sensitization, we now have antibodies to both class I and class II
we have DSAs against HLA B51 and DR4 both are with a significant level
this is very high risk; only can proceed if this is an obligation.
seems to be obligatory as this is an unrelated donor (maybe no suitable related donor available)
taking this in mind we may proceed with transplantation weighing the Irish of remaining on dialysis after explanation of risks to both donor and recipient
In preparing for transplant it is reasonable to turn the crossmatch o negative by plasmapheresis to remove antibodies followed by depleting agent (Rituximab available for B cell depletion), induction with ATG followed by high dose maintenance triple regimen (TAC/MMF/MP)
Broad is 020 without the default but120 with default
Split is121. Without default.
You can revise my reply to
Ben Lomatayo for the HLA match
Sherif Yusuf for Default.
DR4 antibody is DSA despite the recipient and donor has no DR 4 in thier HLAtypin but most probably its due corssreactive group (CREGS)
due to shared epitop between donor DR14 and DR4 antigens.
Sorry I meen the donor DR 14
DR4 antibody is DSA despite the recipient and donor has no DR 4 in thier HLAtypin but most probably its due corssreactive group (CREGS)
due to shared epitop between patients DR14 and DR4 antigens.
Thankyou Manal as you mentioned the patient also has no DR4 antigen
what if he has?
Then they will be auto antibodies detected by the auto crossmatch.
Comment on the report?
The donor-recipient pair has the following characteristics:
First: ABO: Compatible AB (need to Know Subgroups A1B or A2B )
Secondly : HLA mismatch:
** Broad:0-2-0
A31 and A32 are split from A19
A80 is a rare Antigen
DR 13 and DR 14 are splits of DR 6
** Split :
1-2-1
as A80 is rare Ag
Third: Crossmatch:
now positive for both T and B cell
mean presence of antibodies against both Class I and Class II Ag
Fourthly: DSA screening:
DSA against HLA B51 with MFI 4451 (high ) donor-specific
DSA against HLA DR4 not donor-specific
What do you think about the DR mismatch shown in this report?
Broad is 0 mismatch as DR 13 and DR 14 are splits of DR 6
Split is 1 mismatch
Explain the defaulting in HLA A locus?
HLA-A80 is a rare antigen
: Would you accept the offer
It needs a wise decision as high risk of rejection
So if there is paired Kidney transplantation program >> it’s preferred to be included
If Not we can proceed due to the long waiting period and hoping for better survival after intense desensitization protocol with ( Plasma Exchange + IVIG + Rituximab )
with the planning of heavy induction including ( ATG + high dose methylprednisolone )
with Maintenance : ( MMF + prednisolone + Tacrolimus with keeping high level
Protocol for close monitoring of the graft function and early detection of rejection
1-Biopsies Protocol
2-DSA
If not, what are the other options
Paired kidney exchange program
Exellent
can you please reply to my above question if you will proceed with this Tx.
1- Comment on the report?
This is HLA typing and crosssmatch of a potentialdonor and recipient .
ABO : compatible
Broad M : 1 2 0 missmatch
Split M : 2 2 1 mismatch ( AS HLA 31 – 32 are split of HLA A 19 AND HLA
DR 13 – 14 are split of HLA DR 6 )
HLA A 80 is a rare Ag which can be defaulted to HLA 01 ( default 1 2 1 )
FCXM : is positive ( last test ) for both T and B cells
FCXM : auto FCXM is negative for both B and T cells .
DSA +ve for
HLA B51 with MFI 4451 and
HLA DR4 with MFI 3215 .
2- What do you think about the DR mismatch shown in this report?
THERE IS HLA DR 1 broad mismatch and 0 split mismatch because HLA DR 13 and 14 are split of HLA DR 6 .
HLA DR is important in kidney transplantation as complete (2) mismatch has bad frat outcome .
3- Explain the defaulting in HLA A locus
The HLA A is a rare Ag which means can be defaulted to Ag.
4- Would you accept the offer?
Yes , I will accept the offer because patient has a high c PRA which means that this patient may not get better matched offer in near future . but keep in mind that this patient is moderate to high risk ,it needs to explain the risk of rejection in these patients .
5- If yes, how would you manage his immunosuppression?
This patient has significantly high DSA –MFI above < 3000 ( although the cut off value is lab dependent ) means that this patient needs plasma phresis before induction .
Induction : ATG + methyl prednisolone .
Maintenance therapy : prednisolone +tacrolimus +MMF .
Monitoring DSA
Protocol biopsy .
6- If no, what are the other options?
Paired exchange or waiting for anew dodnor offer
Thankyou your match is correct as you included the default straight away.
what is your comment about the DR4 antibodies.
IT is true they are called in the given report as DSAs but the fact is they are not Specific to this Donor so they are NON DSAs better called THIRD PARTY DSAs.
Comment on the report?
ABO compatible
HLA mismatch is 221(split)
020(broad)
Positive FCXM for both T and B lymphocytes which became negative after autocrossmatch
With DSA to class 1 and 2
What do you think about the DR mismatch shown in this report?
One DR mismatch in DRB1
Explain the defaulting in HLA A locus
Because it is rare antigen
Would you accept the offer?
This high immunological risk , should do desensitization with plasmapheresis and rituximab
If yes, how would you manage his immunosuppression?
ATG induction after desensitization and maintenance with triple therapy Tac,MMF and predinsilone
If no, what are the other options?
Paired exchange
correct answer ,you included the default with the split match you need to mention that to fit the required answer in the above question offered with the scenario.
What about the DR4 antibodies.!
It could be due to alloimmunization with such history of pregnancies and blood transfusion or non DSA(third party) antibodies because there’s no HLA antigen typing in DRB4
If it is for DRB1 then consider a DSA so the patient need desensitization
As regards ABO compatibility, both are compatible. Rh status is not important.
HLA Typing.- here we can note that HLA A19 has splits A32 and A33. DRb6 has splits DRb13 and DR B14. HLA A 80 is defaulted as HLA A1. Positive FXCM for B and T cells. cPRA is high at 97%. Positive DSA-B51 with MFI of 4451. DSA for DR4 with MFI of 3215.
HLA Broad match is 1:2:0 and HLA Split mismatch is 2:2:1
Would you accept the offer?
This is very high risk patient with positive DSA, cPRA 97%, Positive FXCM for both B and T cells. I will not offer renal transplant until there is no alternative.
As the patient is high risk , will need desensitisation protocol with PLEX and IVIG. If DSA remain still high then I will add Rituximab . Induction therapy with methyprednisolone and Alemtuzumab. Maintenance therapy with Tacrolimus, MMF and steroids. follow up with protocol biopsy and DSA Check
Paired kidney exchange programme
well done
What about theDR4 please reffer to my above reply.
Comment on the report?
Regarding ABO both are AB
HLA mismatch
Broad: 1 2 0 (A 31,A32 are split of A19) – (DR 13,DR14 are split of DR6).
Split : 2 2 1
Recent cross match is positive for T and B .
T lymphocytes express only class 1 MHC while B lymphocytes express both classes
so the patient either has anti class 1 alone or anti class 1and 2.
HLA B51 (DSA) while HLA DR4 are not DSA.
Regarding this offer:
cPRA is very high so it is difficult to get a suitable donor and the mortality rate on HD is higher for this patient as well than if transplanted so we will go for the transplant after desensitization (plasmapheresis, IVIG and Mabthera) and achieving a –ve cross match.
Then ATG induction then maintaining on Tac , MMF , steroids.
If no: then searching for another donor ; paired kidney donation program.
Dear All
What do you think about the DSA against DR4 in this scenario?
Is it a DSA or Non-DSA (third party) and why?
NB
The HLA antibodies are against HLA DRB1
Possibly a Non DSA (third party)
Because of the extent of possible epitope sharing we cannot exclude epitope sharing as the reason for non-donor specific HLA antibody levels(1)
All DR haplotypes have a DRA gene that encodes the relatively invariant α chain and a DRB1 gene that encodes the β chain of the DR1-DR18 antigens. Some haplotypes carry an additional gene, DRB3, 4, or 5, that encodes the β chain of the DR52, 53, or 51 molecules, respectively. DR haplotypes can be grouped into families defined by the number of DRB genes
mismatching for DRB1 antigens may also include a mismatch for the antigens encoded by the linked DRB3, 4, and 5 loci that encode DR52, 53, and 51, respectively.
Note that some very rare DR1 haplotypes also have the DRB5 gene. Also, an exception occurs on haplotypes bearing DR7 and DQ9. These haplotypes have a null allele at the DRB4 locus and do not express DR53.) So that a patient with a DR1, DR4 phenotype, who is mismatched with a DR11, 12, 13, 14, 17, or 18, is also mismatched for DR52.(2)
Reference
1-Krishnan NS et al.Behaviour of Non-Donor Specific Antibodies during Rapid Re-Synthesis of Donor Specific HLA Antibodies after Antibody Incompatible Renal Transplantation,Plose one2013
2-Zacchary AA et al. HLA Mismatching Strategies for Solid Organ Transplantation – A Balancing Act. Front. Immunol., 07 December 2016
The recepient has no DR4 HLA antigen, therefor antibodies against DR4 are non DSA against third party. Its essentially due to shared epitop between patients DR14 and DR4 antigens.
Sorry, Donors HLA antigens, typo
Excellent
You are the first one to explain it properly
I assume that most of us thought that we are dealing with anti-HLA DRB5-04, and not DR4.HLA-DR4 is an HLA-DR serotype that recognizes the DRB1*04 gene products, which is not the case here where both donor and recipients have DRB1*01 DR13 AND 14. So in this case, the antibodies are non DSA.
Well done
It could be due to alloimmunization with such history of pregnancies and blood transfusion or non DSA(third party) antibodies because there’s no HLA antigen typing in DRB4
If it is for DRB1 then consider a DSA so the patient need desensitization
Well done
HLA antibodies against HLA DR4 is considered a third party (non-DSA) as the donor has no HLA DRB1 04
HLA DRB1 antigens in the donor includes HLA DRB1 01, HLA DRB1 06 (which split into HLA DRB1 13 and HLA DRB1 14)
So DSA against DR will be one of the following DSA to HLA DR 1, HLA DR 6, HLA DR 13, HLA DR 14
Well done
The recepient has no DR4 HLA antigen, therefor antibodies against DR4 are non DSA third party. Its due to shared epitope between patients DR52 and DR4 antigens.
Well done
Regarding DSA against DR4 INTHE SCENARIO?
DR4 is not mention in the scenario but if it mentionh HLA DR Ag has greater alloimmun than HLA A o rHLA B so with high MFI it will result in poor graft out come
Is it aDSA or NON -DSA WHY?
SAB assay for detect DSA pooled panel bead with different HLA class 1 or 2 so that is more specific to DSA against HLA antigens and that why it is not non-DSA (third party)
The HLA-DR typing for donor is HLADR B1*01, HLADRB1*14
The DSA in recipient is for HLA DR4: MFI 3215 (Antibody against HLA-DRB1*04)
This is a non-DSA (third party) as the donor does not have HLA-DRB1*04
it’s Non DSA
it’s may be due to epitope shares between recipient and donor
*it considered a non DSA ( third party )
as the donor has no HLA- DR4
If it is for DRB1 then consider a DSA so the patient need desensitization
-So DSA against DR will be one of the following DSA to HLA DR 1, HLA DR 6, HLA DR 13, HLA DR 14.
HLA TYPING ANALYSIS:
BROAD ANTIGEN MATCHING: 1:2:0
(Rationale being: A31 & 32 are the split antigens for A19; DR13 & 14 are the split antigens of DR6)
SPLIT ANTIGEN MATCHING: 2:2:1
DEFAULT ANTIGEN MATCHING: 1:2:1 (Rationale: A80 is a rare antigen and it is equated /defaulted to the nearest common equivalent A1)
DR MISMATCH:
HLA DR 13 and 14 are the split antigens for DR6 and hence apparently seems to be matched if Broad antigen matching is considered.
But Matching at DR has a great impact on the graft outcome and hence split antigen match need to be given weightage.
DEFAULTING HLA A LOCUS:
HLA A80 is a rare antigen and it is equated /defaulted to the nearest common equivalent A1
ACCEPTING OR REJECTING THE OFFER:
IF YES, THAN WHAT ABOUT IMMUNOSUPPRESSION:
The patient receives induction with Alemtuzumab preferably ( If not high dose ATG). Further IV Ig and Rituximab will be given with in one week of transplantation.
Post Transplant 7-14 days of IV Ig would be needed.
Maintenance Immunosuppression would be with the coneventional Tripple drug immunosuppression (TAC / MMF/ Steroids) – However, TAC dose would be maintained at higher Levels.
IF NO< WHAT ARE THE OTHER OPTIONS:
Would pursue other potential donors or paired Kidney Donation.
I wanted to correct the HLA Matching. Kindly correct the concept of my current understanding.
AIM: To calculate the mismatches
BROAD MATCHING (The word Broad indicates calculating the mismatches after ignoring Splits & also taking Defaults into consideration):
0:2:0 mismatches ( A = 80 is defaulted to 1 ; 32 and 31 are the part of a 19 and therefore regarded as the same antigen)
SPLIT MATCHING (defaults entertained as the same Antigens But splits are regarded as separate antigens):
1:2:1 mismatches
DEFAUL ANTIGEN MATCH: ( defaults entertained as the same Antigens But splits are regarded as separate )
1:2:1
I know that my concept is not fully correct. Appreciate your help in teaching me
Well done
Comment on the report?
What do you think about the DR mismatch shown in this report?
Explain the defaulting in HLA A locus
Would you accept the offer?
This is a high risk transplantation because of positive T and B FXCM, in addition to the presence of DSA and high CPRA (97%). For that I prefer not to do this transplantation unless there is no other option and the patient accepts the risk.
If yes, how would you manage his immunosuppression?
If no, what are the other options?
– The other option is Paired Kidney donation program which I prefer for this case.
Well done
i am confused between this case and the previous case presented in the first week -scenario 1, the first week :
mismatch was 222 for split mismatch which is should be 212 (as B48 is a rare antigen faulted as B40 )
For broad antigen it should be 111 (as B48 is a rare antigen faulted as B40 ) and when defaulted it should be121 but actually, it is written in the report 121 for broad and 111 for default
Do not worry about the fine details. We need to understand the principle
Good-afternoon
my i ask about the significance of HLA -DR4 DSAs with the given MFI levels? this is not related to the donor .
Thanks
Thanks Saja
I understand your question now. The match is always done for DRB1, BUT the typing is done for all antigen. DR4 in this case which is DRB1 (4). is considered a third party DSA as well.
I was not planning to dive into this part as I’m focusing on the typing. I will put is as question.
Thank you prof Ahmed
Dear All
Do we consider DRB3, DRB4 and DRB5 in the match?
HLA-DRB3/4/5 are linked to HLA-DRB1. In Renal transplantation there is a diminishing significance of HLA antigen with time because of the immunosuppression.
Several studies suggest that HLA-DRB1 mismatching is particularly deleterious, perhaps because HLA-DRB1 is a marker of closely linked HLA antigen loci, which were not considered (HLA-DRB3/4/5).
Matching of HLA-DRB3/4/5 may be considered in specific patients who have an exceedingly low probability of transplantation, such as ethnic minorities and HLA-DRB1 mismatch. Those should undergo transplantation regardless of HLA-DRB1 mismatch.
Finally Matching for HLA-DRB3/4/5 showed improved outcomes of unrelated hematopoietic stem cell transplantation.
References:
The HLA loci DRB3, DRB4 and DRB5, are paralogs of locus DRB1. Thus, they share a significant fraction of their genetic sequence with DRB1.
While they exhibit fewer polymorphisms than HLA-DRB1, show moderate variability and are only present in a subset of individuals, antibody testing is needed as they are thought to play a role in transplant rejection.
Reference:
Habets Th, Hepkema B, Koperi M, Schnijderberg M, Smaalen T, Bungener L, et al. The prevalence of antibodies against the HLA-DRB3 protein in kidney transplantation and the correlation with HLA expression. PLOS ONE. 2018 Sep.
DRB1 is the most important, as its associated with strong Anti HLA DSA in incompatable transplant. But HLA typing is usually performed for all.
Dear All
This is the link https://www.youtube.com/watch?v=VPtnjWLhC2U
Also you can log into Prof Ahmed Mostafa lecture I sent to you, it is more simplified
Thank you
☆Comment on the report?
_____________________________
Concerning this pt/ donor report:
A) They are compatible in ABO blood group
B)HLA mismatch in ABDR is as follow:
1. Broad: 0.2.0
(HLA A80 is a rare antigen so, it is defaulted to A1 and A31 ,A32 are splits for broad antigen A19. DR13 and DR14 are splits for DR6).
2. Split 2.2.1
3. Defaulted: 1.2.0 (A80 is defaulted to A01)
C) FCXM and FCXM auto:
▪︎Serial historical positive T cell TCXM ( due to autoantibodies)
▪︎The last crossmatch is positive for both T and B cell: denoted to DSA for both HLA class I & II antigens.
D) DSA screening:
▪︎DSA for B51 with MFI 4451
▪︎Non-DSA for HLA-DR4 with MFI 3215
☆What do you think about the DR mismatch shown in this report?
_______________________
DR 01 is shared between pt and donor
DR 13,14 split of DR6. So, this a good match
☆Explain the defaulting in HLA A locus
______________________________
The HLA-A80 is a rare antigen, so it is defaulted to the nearest HLA Ag which is A1.
Would you accept the offer?
__________________________
Yes,
☆How would you manage his immunosuppression?
______________________
▪︎Desensitization protocol (Plasma pharesis, IV Ig and Rituximab).
▪︎ Induction with ATG and maintenance immunosuppression( steroids, tacrolimus, and MMF).
▪︎Follow up with: CBC, urine analysis, Tacrolimus level and serial investigations for DSA.
▪︎Follow this pt for recurrence of MPHN nephropathy.
Exellent Tahani are you going to consider those non DSAs if yes how in the context of desensitising this R.
Comment on the report?
ABO compatible donor with recipient AB but Rh not .
HLA typing:
HLA mismatch
split : 2 2 1
broad: 1 2 0 (A 31,A32)split of A19, DR 13,14 split of DR6.
Broad defaulted : 1 2 O
.
Flow cross match:
historic cross match positive for T lymph, negative for B lymph
recent cross match positive for T and B .
T lymph contain only class 1 antigen while B lymph contain both class 1 and 2
so historic crossmatch positive for T , negative for B ( either lab error or auto Ab since B lymph contain HLA 1 and should be positive with T lymph) .
but recent cross match positive for both (so patient either has anti class 1 alone or anti class 1and 2.
DSA screening :
Anti HAL B51 MFI 4451 (DSA).
Anti HLA DR4 MFI 3215(non DSA).
What do you think about the DR mismatch shown in this report?
DR 13,14 split of DR6(split Ag in modern era of immunology, in the common broad Ag)
.
Explain the defaulting in HLA A locus ?
HLA80 rare antigen corrected or defaulted to (A1) since it share the same binding IGg site (public epitope).
Would you accept the offer?
for me accept the offer for the following causes :
1-patient highly sensitized so the mortality on HD more than transplant after (desensitization regimen) .
2- c PRA more than 95 so it is difficult to get suitable donor neither with kidney paired donation nor with allocation system (need to search more than 30000 donor ).
so we go ahead for transplant after full explanation for patient the risk and he should accept the risk .
If yes, how would you manage his immunosuppression?
full desensitizing regimen include (rituximab , IVIg, plasma exchange ).
, ATG induction , and maintenance drug ( TAC ,MMF steroid ).
If no, what are the other options?
long waiting list till the allocation system get suitable donor if patient lucky
mean while do desensitization regimen.
Thanks, Dr Talib
Comment on the report?
-Both donor and recipient are ABO compatible.
-HLA-typing:
-HLA A19 split into A30 ,A31 ,A32,A33.
-HLA DR6 split into DR13,DR 14.
-Broad mismatch:0.2.0
-Broad mismatch(defaulting) :1.2.0 (HLA-A 80 is defaulted to A-1)
-Split mismatch :1 .2 .1
-Historical T/ FCXM was positive while B /FCXM was negative .
-Auto T/FCXM is positive (autoantibodies) and negative.
-Current T and B/ FCXM are positive.
-DSA screening showed DSA against HLA B51/ DR4.
What do you think about the DR mismatch shown in this report?
-HLA DR6 split into DR13, DR 14.
-HLA DR mismatch is associated with poor graft outcomes.
-Explain the defaulting in HLA A locus
HLA-A 80 is a rare antigen and defaulted to A1
Would you accept the offer?
No, because he is a high-risk patient.
If yes, how would you manage his immunosuppression?
-Desensitization( Plasma exchange +IV Ig±rituximab) of the patient until FCXM becomes negative.
-Induction with ATG, and maintenance immunosuppression Tac, MMF, steroid
-Monitoring of DSA.
-CBC, urine analysis.
-Tac level.
If not, what are the other options?
-Search for another donor or enroll in a paired exchange program.
-Deceased donor.
Thank you for trying but the correct answer is
Broad 020
Split 121
Adding the default to the broad it will be120
TO understand how this was reached refer to my reply to BAN LOMOTAYMO earlier on.
Sorry Ben Lomatayo
This recipient and donor are matched for blood group, although have different rhesus factor, this does not matter in transplantation.
HLA matching
The patient has 2;2;2 mismatch for HLA-A,B and DR
HLA-A 80 is defaulted to A-1
HLA- A 31 and 32 are splits A19.
HLA-DR 13 and 14 are splits of DR6
Broad mismatch 0, 2,1
Splits mismatch 1,2,2
There are also 2 mismatches at HLA-C,DQA1, and 1at HLA-DQB1
Crossmatch
The patient had a positive T flow crossmatch in 2017 likely due to an autoantibody as the auto crossmatch was also positive. This later on became negative on subsequent testing.
The T cell crossmatch become positive afterward and later on the B cell crossmatch also became positive likely due to sensitization.
The patient has DSA to HLA-B51 with a borderline high MFI and DR4.
HLA-80 is a rare antigen which is defaulted to A1
I would accept the offer because this patient is highly sensitized and has a very low chance of receiving a transplant
The first option would be to consider the patient for paired exchange with a donor who doesn’t have unacceptable antigens.
The second option would be desensitization to reduce the level of DSA and then induction with either Alemtuzumab or ATG.
Maintenance with triple immunosuppression with prednisolone, MMF and Tacrolimus
Thanks
Broad is not right
# Comment on the report?
This leady consider as highly sensetized patient had received kidney from un related donor, with compatible blood group(AB Neg. ,AB Pos.) .There is history of blood trandfusion, pregnancy, high CPRA 97% with positive DSA for class 1(HLA-B 51 with MFI 4451) and non DSA for class11(HLA- DR4 with MFI 3215)
HLA mismatch:
Broad mismatch (0-2-0 ) because HLA – locus 19 split (31,32)
HLA-DR locus 6 split (13,14)
HLA -A 80 is rare Ag so defaulted in HLA- A 01
Default mismatch(1-2-1)
split mismatch (2-2-1)
Crossmatch:
history of positive T- cell due to autoantibodies and without autoantibodies
Current serum showed positive FCXM for both T,and B cells
# What do you think about the DR mismatch shown in this report?
DR 13 &14 splits from DR 6 locus ,so the DR mismatch is (0) on broad and (1) on split mismatch
# Explain the defaulting in HLA A locus
HLA- A 80 is a rare antigen, so we can defaulted to HLA-A 01
# Would you accept the offer?
No,I wouldn’t accept such patient due to higher posibility of AR and chance of recurrence of the original disease (MPGN) after transplantation
# If yes, how would you manage his immunosuppression?
high dose intravenous immunoglobulin (IVIg) or low dose IVIg in combination with plasmapheresis +ATG+ maintenance (Tac ,MMF, steroid)
# If no, what are the other options?
Change to other suitable donor or paired exchange program
Nearly there, but MPGN is not the main reason for rejecting the offer.
Comment on the report?
ABO compatible
HLA mismatch
1-broad: 2 2 1
2- split 1 2 1
3- default 1 2 0/ 0 2 0
My Q
Default mismatch must be the list mismatch number, so it must be less than broad mismatch, is not it?
Therefore; A80 defaulted to A1
A 31 & 32 they are one? they are A 19 so A=0 mismatch default and broad
DRB1: 13 & 14 they are DR6 so DRB1 = 0 mismatch broad
Finally Broad 1 2 0
after default 0 2 0
it seems confusing to me yet??
positive FCXM and high c PRA (c pra put him on low chance to get acceptable) deceased donor)
DSA positive with high titer
MPGN may recur post-transplant
the donor is a living donor so there is time to do desensitization therapy for the recipient to render him negative crossmatch
Plasmapharesis+low dose IVIG +Rituximab
the induction will be with ATG + methylprednisolone
Maintenance with Prograf+cellecept+prednisolone
Monitor with DSA and protocol biopsy post-transplant
if not to accept this donor?
I will go to paired kidney donor
for me, I will not accept this donor? taking into consideration the donor risk
Thanks for trying Jamila, you are nearly there, but not quite right. The broad is wrong
Default 1 2 0
Broad 0 2 0
How default 3 MM and broad 2
And the aim of default is to decrease MM ! IS NOT IT?
Would you accept the offer?
If yes, how would you manage his immunosuppression?
If no, what are the other options?
This very diificult question, with this scenario, positive cross match and positive DSA , it means very risky transplantion and possibilty of acute rejection is very high,
but considering the pt age and low chances of having a kidney with this high cPRA(97%) i will accept if the paired kidney donation programm is not feasible in this sitauation.
I will give him the chance by using desentization protocol,using plex with iv igg low dose with rituximab and i will go for ATG induction and may go for almetuzmab
Well done
As expected