3. Please comment on the crossmatch report below and advise us whether you are happy to proceed based on the results shown blow or not. Both donor and recipient and suitable for the procedure.
- NB: This crossmatch is negative (authorised).
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3. Please comment on the crossmatch report below and advise us whether you are happy to proceed based on the results shown blow or not. Both donor and recipient and suitable for the procedure.
Dear All
We need to know the DSA level. Desensitisation is not indicated UNLESS the crossmatch is positive. The presence of DSA with a negative crossmatch is not an indication for desensitisation.
Compatible blood groups
HLA typing:112mismatches
T and B cell FCXM negative
I will go with thyroglobulin in induction if he is the only available donor
But the issue is that the patient has no matches in DR which will increase risk of acute rejection and needs frequent follow up with DSA and this may need protocol biopsy
In maintenance immunosuppression we can use tacrolimus ,MMF and pred
Blood groups : compatible
HLA mismatches:100
No PRA or sensitization history
This is a virtual cross match
I will not go for transplantation except if there is physical cross match FCXM and PRA
advantage of virtual crossmatch saving time, reduce the cold ischemia time. disadvantage: may give false positive with denatured HLA epitopes, weak DSA and allele-specific(non-DSA).
Sorry this answer is on another scenario
In second transplantation:
the importance of the strength of DSAs for development of AMR. Currently, we screen all transplant candidates for anti-HLA antibodies using Luminex single-antigen beads for the specificity and the strength of antibodies at our center (Einstein/Monte- fiore Transplant Center Anti-HLA antibodies with MFI values 5000 are reported to the United Network for Organ Sharing as unacceptable antigens. Patients with living-donor candidates but positive cross-match and/or DSAs are first considered for our internal KPD exchange program, and then the National Kidney Registry paired-exchange program. If KPD exchange is not feasible and patients are interested in a desensitization protocol, we then use the following algorithm:
1. CDC T cell cross-match-negative but CDC B cell cross- match and/or flow cytometry T and or B cell cross- match-positive patients with total T and B cell flow cytometry MCS values 300 and MFI DSA values 5000 receive transplant with thymoglobulin and high- dose IVIG (2.0 g/kg) without PP.
2. CDC T cell cross-match-negative but CDC B cell cross- match and/or flow cytometry T and/or B cell cross- match-positive patients with total T and B cell flow cytometry MCS values 300 and/or MFI DSA values 5000 receive pretransplant desensitization including PP, IVIG, and rituximab. Patients start immunosuppresive treatment with tacrolimus, mycophenolate mofetil, and prednisone and one dose of rituximab (375 mg/ m2). They receive four sessions of PP every other day starting 1 week after rituximab treatment. One dose of IVIG (2.0 g/kg) is given after the fourth dose of PP. Patients receive transplant if MFI and flow cytometry MCS values decrease to 5000 and 300, respectively.
3. CDC T and B cell cross-match-positive patients are con- sidered for desensitization if they have less than three DSAs and only one DSA with MFI values 5000 with the same protocol described above.
References:
1. Port FK, Wolfe RA, Mauger EA, Berling DP, Jiang K: Compar- ison of survival probabilities for dialysis patients vs cadaveric renal transplant recipients. JAMA 270: 1339–1343, 1993
2. Russell JD, Beecroft ML, Ludwin D, Churchill DN: The qual- ity of life in renal transplantation—A prospective study. Transplantation 54: 656–660, 1992
3. Wolfe RA, Ashby VB, Milford EL, Ojo AO, Ettenger RE, Ag- odoa LY, Held PJ, Port FK: Comparison of mortality in all pa- tients on dialysis, patients on dialysis awaiting transplanta- tion, and recipients of a first cadaveric transplant. N Engl J Med 341: 1725–1730, 1999.
4. Akalin E: Posttransplant immunosuppression in highly sensi- tized patients. Contrib Nephrol 162: 27–34, 2009
5. Hakim RM, Milford E, Himmelfarb J, Wingard R, Lazarus JM, Watt RM: Extracorporeal removal of anti-HLA antibodies in transplant candidates. Am J Kidney Dis 16: 423–431, 1990
6. Pescovitz MD: Rituximab, an anti-cd20 monoclonal anti- body: History and mechanism of action. Am J Transplant 6: 859 – 866, 2006
7. Perry DK, Burns JM, Pollinger HS, Amiot BP, Gloor JM, Gores GJ, Stegall MD: Proteasome inhibition causes apopto- sis of normal human plasma cells preventing alloantibody production. Am J Transplant 9: 201–209, 2009.
Crossmatch interpretation:*ABO compatible .
* II2 mismatch HLA-A, HLA -B, HLA DR) .
* other mismatch ( HLA-c HLA-DQA1 HLA-DQB1 HLA DPB1)
*FCXM negative for B and T cell.
* Past history for transplantation make patient highly sensitised.
*DSA screening by luminex SAB
* if positive, desensitisation must done by IVIG or plasma exchange.
* if negative will proceed transplantation.
With induction by ATG and triple therapy MMF Tacrolmus and steroid .
*After transplantation monitor DSA or protocol biopsy .
Matching reveals ABO compatibility with HLA A,B and DR mismatch 122.FCXM negative for T and B. There is high risk as HLA DR B1 mismatch has worse graft outcome due to DSA formation. In addition there is sensitization due to previous Tx .If no another better kidney offer, we proceed for Tx with aggressive induction with ATG, full triple maintenance immunosuppression(TAC ,corticosteroid and MMF) with additional precautions of DSA monitoring and protocol biopsy.
Both are A+
HLA-A,B and DR 112 mismatch
Negative FCXM crossmatch for both T and B CELL
We should calculate DSA level .
The patient and the donor are ABO compatible, 112 mismatch in HLA-A,B,DR, with negative flowcytometry. Level of DSA should be done. The patients is considered sensitized due to the history of previous transplantation ( memory T cell ) and the outcome of this graft will be at risk due to the poor HLA matching with 2 mismatch at HLA-DR, so if we will proceed ATG as an induction should be used with triple immunosuppression therapy and regular monitoring of DSA , and protocol biopsy.
ABO compitable they have same blood group
HLA 1.1.2
this is second transplantation
+HLA B&C mismatch associated with poor graft survival
+HLA DR high risk of acute rejection & poor survival of the graft
virtual cross match negative
DSA screening should be done and if low MFI proceed with no desensitization
patient high risk due to DR mismatch
heavy induction recommended with depleting agent & according to me I’ll not proceed for this procedure
ABO compatible with negative FCXM of both T and B cells ,with 122 crossmatch of HLA -A,B and DR also there is a mismatch at C, DQ and DP
The recipient with second transplant so there is a risk of highly sensitisation which will lead to increase risk of acute AMR and graft loss .
DSA screen by single Ag bead test luminex must be done and if it’s positive desensitization must be done otherwise keep him on triple immunosuppressants with ATG induction.
Presence of HLA -C positive in combination with HLA-B will affect on graft survival and HLA- DQ mismatch is associated with development of denovo DSA which can cause acute and subclinical AMR and graft loss.
This is second TX, compatible ABO TX, 4/6 mismatch for HLA-A, B, DR and negative FCXM. We don’t know if there is DSA or not. But there is no repeat mismatch with the previous TX in 2002 which makes the probability of DSA existence low. Patient have been on waiting list for a long time. Although 4/6 mismatch makes the outcome of the graft worse than a full or one-mismatch one, but remaining on the waiting list for such a long period of time, make the worst outcome. So, I prefer to proceed to transplantation.
both donor and recipient has the same blood group A+
HLA mismatch is 1.1.2
A C DR
recipient 2-25 15-27 11-11
donor 2-11 15-57 1-7
flow cross match is negative despite the patient had a previous transplant on2002
i prefer to have another donor because of 2 DR mismatch
if there is no other donor and i have to proceed with the transplant with considering Luminex after checking the cut off value of FCXM.
I will deal with the patient as high risk( a second transplant which may lead to memory cells).
I noticed he did multiple cross match check between the years2008-2020. why he did that? may be this is just routine follow up test but it could be because he had graft failure early on and he was on a waiting list since 2008 which is a long time. or it could be he had multiple blood transfusions which make him highly sensitized
induction with ATG, maintenance with triple therapy (tacrolimus, MMF& steroid)
the patient needs meticulous follow up after transplantation because he is at high risk of AMR
ABO compatible
112 mismatch
mismatch at HLA-c, DQA1, DQB1 and DPB1
negative B and T cell crossmatch
second transplant
The degree of mismatching is associated with long term graft survival
HLA-DR and B mismatches correlate with poor graft outcome
HLA-DP antibodies are more common in patients with previous transplantation and associated with decreased graft survival in recipients of second transplant
DQ mismatches are associated with increased risk of rejection and poor graft outcome
DSA screening by Luminex should be done to stratify the immunological risk
Studies suggest that transplantation of an HLA incompatible kidney provide better survival benefit compared to waiting and never receive a kidney
the transplant is considered high risk and it is better to find another more matched donor, if not available proceeding to transplant will be better.
Philogene, M.C. and Brennan, D.D.C., Kidney transplantation in adults: HLA matching and outcomes. UpToDate
Leeaphorn, N., Pena, J.R.A., Thamcharoen, N., Khankin, E.V., Pavlakis, M. and Cardarelli, F., 2018. HLA-DQ mismatching and kidney transplant outcomes. Clinical Journal of the American Society of Nephrology, 13(5), pp.763-771.
Orandi BJ, Luo X, Massie AB, et al. Survival Benefit with Kidney Transplants from HLA-Incompatible Live Donors. N Engl J Med 2016; 374:940.
ABO matching
H L A 112
Negative FCXM for both T and B cell .
The pt had very poor HLA mismatch 4 out of 6 ,DR B 2 which associated with poor graft survival .
We should screen the pt for DSA .
This pt consider as high risk ,induction by ATG and maintenance with MMF,TAC and prednisolone .
There is 122 mismatch
Negative B and T cell FCXM
Although HLA incompatibility carries worse prognosis ,yet its not an absolute contraindication for transplantation provided that we use depleting induction therapy proper maintenance immune suppression,
Desensitization will depend on DSAs level and intensity
Studies have compared outcomes related to no. Of mismatches revealed no significant difference regarding acute rejection and graft functions up to 3 years follow up between both groups
Procurement and Transplantation Network/United Network for Organ Sharing Kidney/Pancreas Transplantation Committee (2002) Survival of mandatorily shared cadaveric kidneys and their paybacks in the zero mismatch era. Transplantation 74: 670-675.
Foss A, Leivestad T, Brekke IB, Fauchald P, Bentdal O, et al. (1998) Unrelated living donors in 141 kidney transplantations: a one-center study. Transplantation 66: 49-52.
The recipient-donor pair are matching at the ABO system
Mismatched at the level of classical HLA Ag loci 112(HLA -A ,-B,-DR)
And also mismatched at many non-classical HLA Ag(HLA-C, HLA-DP B1,- DQB1,-DQA1.)
FCXM was negative (T and B cell )
The patient has hx of px renal transplantation.
There is high HLA mismatch between donor and recipient who is already highly sensitized due to previous transplantation
HLA-DR mismatch associated with poor graft survival especially when associated with HLA-DQ mismatch
HLA-DQ mismatch associated with increase risk of rejection and graft loss.
HLA-DP mismatch associated with high risk of rejection of the 2nd transplantation but not the first
So in order to re -transplanted the patient I will ask about the previous result of crossmatch
Do CPRA
Repeat crossmatching
Looking for DSA by doing Luminex-SAB(SPI)
Know the strength of DSA
If present so we must go ahead for desensitization by plasma exchange and IVIG
Induction by ATG
Use of Triple IS for maintenance
And monitor DSA by protocol graft biopsy
ABO matched pair
HLA 1 1 2 mismatched
There others HLA mismatched at ;HLA C, DQA1 ,DQB1 and DPB1
Negative FCXM for both T and B cells.
Patient is sensitized from the previous transplant .
Kidney transplantation is not absolute contra indication for this patient . Although 2 HLA DR B1 mismatch is associated with inferior graft out come and HLA DP A is associated with poor graft out come in re transplant . HLA C mismatched is also found to be associated with ABMR in the first year post kidney transplantion .
This patient should be screened for DSA by luminex . If negative we can go ahead for transplantation with ATG induction ,maintenance triple TAC with close monitoring of DSA and protocol biopsy.
Reference ;
Up to date September 28 , 2021
Although there are the most polymorphism in HLA-A, -B, -DR, particularly HLA-DR, and mismatching for them has been associated with higher risk of HLA sensitization, other HLA mismatches may be important as well. For example, HLA-DQ mismatch has been associated with an increased risk of rejection and is a risk factor for the development of de novo DSA, mismatching for HLA-c among those with PRA>10% has been associated with decreased graft survival, and reduced allograft survival with HLA-DP mismatch has been reported as well.
The patient is ABO matched, 112 HLA antigen mismatch, with 4 other extra mismatches, but the flow crossmatch was negative several times.
Because of the broad HLA mismatch, DSA assay with more precise and sensitive technique such as solid phase SAB assay with MFI quantification is suggested. And it is better for interpretation of HLA DSA, major cross reactive groups (CREGs) are taken into consideration.
If a more HLA matched donor is available, it will definitely be the better choice.
A major limitation of FCXM is the difficulty in defining the specificity of the anti-HLA antibody, particularly for highly sensitized individuals.
The causes of negative flow cytometry should be taken into consideration.
Such as the lowest burden of DSA, and the presence of an antibody that is specific to an allele that the donor does not have.
2nd kidney tranplantation with 112 mismatch full class 2 mismatch which associated with low patient and graft survival.
I will go for single antigen bead.
If the patient was highly sensitized with very low possibility to find him a better matching i will accept this donor with depleting induction ATG and triple conventional immune suppression medications tac/mmf/steroids and keep monitoring of donovo DSA.
If the patient wasn’t highly sensitized and he may has a better matching.i discuss this issue with the patient and its better to get him a better matched donor.
The pair are blood group A +ve .
HLA-A,B and DR 112 mismatch
There is also mismatch at HLA-C DQA1 DQB1 DPB1
Negative FCXM crossmatch for both T and B CELLS .
Patient is at high risk of being sensitized by previous transplantation at 2002.
And no data about his mentinance on low dose IS after graft failure.
2 DR mismatches is associated with low patient and graft survival.
In many patients with late antibody-mediated graft loss, even when HLA class I alloantibodies are detectable, circulating HLA class II de novo DSA are considered to be mainly responsible for rejection. Therefore, most authors believe that specifically HLA class II mismatches (not only HLA-DR but also HLA-DQB, DQA, and DP mismatches) confer an increased risk for late graft loss .
Due to the strong linkage disequilibrium between the DR and DQB or DQA (but not DP) gene loci, two DR mismatches often indeed represent 6 mismatches that are relevant for induction of DSA.
HLA DP mismatche affected second transplantation more that first onr
Also pretransplant HLA-C DSA may be more likely to develop ABMR during the first post transplant year.
So in this case there are multiple risk factors that will lead to low outcome of graft survival
This doner is not the best option for the recipient due to risk of developing de novo DSAs in the first year post transplantation
But if we have no other options
Screening for DSA by Luminex befor transplantation If DSA is positive, the patient needs desensitization.
induction pretransplant and DSA detection at 3 and 6 months post Tx if positive bipsy should be done and if the biopsy result is positive, treatment of AMR is recommended.
Mentinance of triple Is steroid,tacrolimus and MMF.
Wiebe C, Gibson IW, Blydt-Hansen TD, et al. Evolution and clinical pathologic correlations of de novo donor-specific HLA antibody post kidney transplant. American Journal of Transplantation. 2012;12(5):1157–1167.
GOOD
Woww
Excellent answer, short concised no waffle.
Thanks prof
Excllent
Thanks prof
*1.1.2 mismatch. (.A.B.DR)
*Negative crossmatch.(both T,B)
*Previous transplantation at 2002 so we need to DSA state of our patient by flow cytometry
*Mismatching for HLA-A, -B, and -DR has been associated with a higher risk of HLA sensitization in both adult and pediatric patients who are relisted for a second kidney transplant
* HLA-DQ and -DR, have been found to be a risk factor for the development of de novo DSAs.
*patients with high levels of pretransplant HLA-C DSA may be more likely to develop ABMR during the first posttransplant year
*Anti-HLA-DP antibodies are less common than antibodies to HLA-DR and -DQ, occurring in 5 to 14 percent of transplant recipients
The frequency of HLA-DP antibodies increases in patients who were previously transplanted, occurring in up to 45 percent of retransplanted subjects
*Although some studies have suggested that the presence of HLA-DP antibodies does not reduce allograft survival among recipients of a first transplant but other studies have found that HLA-DP antibodies correlate with reduced allograft survival among recipients of a second transplant
If DSA negative we can preceed transplantation without sensitizations with close monitor of DSA titer
Induction with ATG
Maintenance with MMF.TAG,Steriod.
Reference
Up to date Sep 28, 2021.
Well done Dalia
I will quote this statement from you. “Although some studies have suggested that the presence of HLA-DP antibodies does not reduce allograft survival among recipients of a first transplant, but other studies have found that HLA-DP antibodies correlate with reduced allograft survival among recipients of a second transplant”
This seems to be a virtual mismatch of deceased donor offered for some probable recipients from the list, one of whom is our patient. there is only one match DRB4/6 which is as far as I remember wide. so in terms of allele groups there are similarities but in terms of specific groups (second numbers), there are dissimilarities. In sum it is only one match. additionally, it is second transplantation. 28/07/2020 flowCXM is invalid but all others are negative. still there is high risk of DSAs.
I would prefer another recipient.
In case of an obligation to use for this patient for any reason, as it is cadaveric I may go with it with depletion of lymphocytes by rATG high dose (???) induction followed by triple protocol for maintenance with close monitoring
It is FCXM
-Both donor and recipient blood group A +ve Rh, so they are compatible.
-This is the second transplant for this patient which means risk factor for sensitization of the patient.
-Donor and recipient HLA –A, B, DR is 112 mismatch.
-2 HLA-DR mismatches can affect patient and graft survival and HLA- DR mismatch is relevant induction to DSA.
–Also there is a mismatch inHLA- C, DQA1, DQB1, DPB1.
-HLA class II mismatch (not only HLA-DR but also DQA, DQB, and DP mismatch) lead to the development of de novo DSA, AMR, and graft loss.
-Negative B and T cell flow crossmatch.
–are you happy to proceed based on the result shown or not?
-This patient has 2 HLA –DR mismatching, if we can find another donor it will be better than an available donor. If there is no other donor:
-Firstly we need to screen this patient for preformed DSA using Luminex-SPI( which can detect a low level of DSA )because of this second transplant for this patient. Inspite a lot of studies showed that no difference between Luminex positive and flow crossmatch negative patient and DSA negative patients in graft survival, acute rejection, and patient mortality.
-If DSA is positive, the patient needs desensitization.
-Patient is a high-risk patient so needs induction with ATG.
-If DSA is negative, we can proceed to transplant directly.
-patient needs to follow for de novo DSA level.
-Maintance IS can be MMF, Tacrolimus, prednisolone.
Thanks, Reem
Well done
This ABO compatable match
T, B cells FCXM negative
Previous transplantion 2002 with no previous mismatch prior to first transplant
currnet assay shows multiple mismatches in both class 1 , 11 including HLA DR 2 and additional HLA -c , DQA1,DPB1 mismatch for second transplantaion , no information about DSA s assay .
we need to assess the DSA level by luemnix SAB and emphazise about the HLADP antibodies density as this is second transplantion .
Anti HLA antibodies to DP were estimated to be 35% lower than that of A, B and DR and mostly due to previous trans-plantation rather than pregnancy [2] many recent cases reports address the controversies about the impact of HLA DP antibodies in allograft outcome, recent study reported reasonable outcome with ATG or Alemtuzumab induction followed by Tacrolimus, MMF and prednisolone without prior antibody removal in 3 cases with second TX from DBD in sensitazed recpient with postive crossmatch due to HLA-DPAB ,with out desenzitaion protocal (1) while other studies shows poor outcome with high risk of acute and chronic ABMR (2)
patient high immunological risk need to be assesed for the need of desensitzation with lumenix SAB assay for DSA density prior to second transplantion and induction with ATG , or almetuzmab with triple maintenace IS with tacrolimus , mmf prediolone and post transplant DSA monitroing.
1-Renal transplantation against a positive crossmatch due to HLA-DP
Donor-specific antibodies without prior antibody removal – Case report
Yazin Marie a,1,*, Tim Key b,2, Ahmed Halawa a,c, transplantation reports6 , 2021
2-Single center observation of the role of pre-existing HLA-DP antibodies in humoral rejection following renal transplantationAuthor links open overlay panel
NikaeinA.aLermanM.bRofaielG.cdAllamS.R.c
Your references do not relay the present scenario. This is a cross match match negative scenario with high mis match. Would you transplant?
Thanks, Hemant
Saja is referring to the case if there is significantly high DSA ” patient high immunological risk need to be assessed for the need of desensitization with Luminex SAB assay for DSA density prior to second transplantation and induction with ATG, or alemtuzumab with triple maintenance IS with tacrolimus, MMF prednisolone and post-transplant DSA monitoring”.
-Regarding the cross matching report:
ABO cross matching is compatible
HLA A B DR 122mismatch
HLA C DQ A1 DQ B1 DPB1 mismatched
Negative B and T cell flow cytometery crossmatching
-With the availability of potent immunosuppressive agents that improved the graft survival rates, the impact of HLA compatibility seems to be minimized .But the European Renal Best Practice Transplantation Guidelines still recommended that matching of HLA-A, -B, and -DR whenever possible, emphasising on HLA-DR locus as HLA-DR mismatches were significantly associated with higher risk of overall graft failure. (1)
-So in this case
The transplantation is considered high risk and desensitization with ATG will be needed and maintenance agents tacrolimus ,MMF and steroids can be offered
Also DSA by Luminex technique need to be assessed
Reference
Shi X etal. What is the impact of human leukocyte antigen mismatching on graft survival and mortality in renal transplantation? A meta-analysis of 23 cohort studies involving 486,608 recipients. BMC nephrology 2018;19.116.
“desensitisation with ATG” please explain the mechanism?
Also read this article https://cjasn.asnjournals.org/content/clinjasn/6/4/922.full.pdf
Patient and donor have compatible ABO blood group (both A positive)
Flow cytometry- negative
HLA typing showed
HLA-A: 1 mismatch
HLA-B:1 mismatch
HLA-DRB1:2 mismatch
Extra to note:
HLA-DQA1: 2mistmatch
HLA-DQB1:1 mismatch
HLA-DPB1:2 mismatch
NO Single -phase assay to show DSA
Interpretation:
Increamental HLA DR mismatches has significant effect on graft survival amd its shown to be associated with incidence of hodgkin lymphoma and hip fractures as a result of higher IS therapy
ANZDT registry found that HLA- DQ mismatches has been associated with increased risk of acute rejection. The effect further amplified if when there is HLA-DR mismatch together.
HLA-DPB has effect on the transplantation survival but only for second tranplantation but not the first, possible due to HLA-DPB epitomes and undetected immunologic priming against donor-DP mismatches of failed graft.
Regarding the scenario,
Patient had previous transplant 2002 which indicates sensitising event.
This patient has ABO compatible donor but with HLA-DR ( 2 mismatches) with HLA-DQ mistmatches which will have impact on allograft survival
Patient also has HLA-DPB mismatches which will have impact on her second transplantation.
Information on DSA is lacking which might determine the MFI to determine antibody removal prior to transplant and post transplantation DSA monitoring for the patient
So, I would say this patient is high immunological risk for rejection
Choices:
1- rTAG as induction therapy with maintenance with tac, MMFand steroids. Post transplantation suggest to monitor DSA or protocol biopsy for early detection of AR
2- Paired kidney exchange to find more suitable donor ( acceptable mismatch donor)
3-antibody removal prior to transplant if DSA detected
Covered most points but explain “antibody removal prior to transplant if DSA detected” in this cross match negative patient. what is the evidence ?
This patient is prepared for his second transplant from a potential donor with
– ABO compitable
– HLA mismatch 112 ( including Dr) as well as mismatch in HLA DQA1, DQB1, DPB1 and C
–
– negative FCXM , no reported DSA
This is a high risk transplant , DSA must be assessd by Solid-phase immunoassay (Luminex) if no DSA , we can proceed with transplantation and induction with ATG followed by triple Is ( steroid , MMF and TAC ).
NB., Our center wouldn’t accept this donor , we don’t accepted Dr mismatch
cross match report for this couple shows:
ABO compatible donor-recipient(A+).
112 HLA mismatch (1 at A locus, 1 at B locus, 2 at DR locus)
Other mismatches including HLA-C, HLA DQ A1, HLA DQB1, HLA-DPB1
Both T and B cell flow cytometry cross match was negative
Past history of previous renal transplantation in 2002(no mention about DSA) present.
Despite the negative FCXM, we need to ask the tissue typing lab to go for a luminex assay to identify the specificity and strength of any performed DSA (from previous transplantation) for this particular donor.
This will help to risk stratify the patient(around 7% of the cross match is false negative and carries risk to the recipient) but may not preclude transplantation being in the best interest of this patient as this sensitized patient may have difficulty to find a suitable graft) but the outcome of DSA positive patient is inferior to DSA negative patient in terms of graft survival and acute rejection episodes(desensitization may be required)
This patient will need an induction with ATG(high risk), and triple drug immunosuppression (Tacrolimus, MMF and steroids) with follow up Post-transplant for DSA
Dear All
What do you need to stratify the risk? I did not provide all information. What would you ask the tissue typing lab to check?
Keep trying
I need more information about the ethnic back ground , previous Induction IS , Primary disease , whats the cuase of failed first transplantion?
This is second transplant , ABO Compatable , with 1.2,2 mismatch , need to screen for DSA by luminexSAB and assess for the need of desenatization prior to second transplantation .
Induction with ATG followed by Triple standard IS with tacrolimus , MMF , steriod .
1-I will ask about how much the MFI of the DSA, especially against the DQ antigen. if it is high, we may need to give IV iG and close monitoring of the level post-transplantation or go for protocol biopsy.
2- there is controversy about the DSA against DP. some centres proceed with transplantation even with positive DSA against DP antigen(low polymorphic antigen) as long as FCXM is negative.
3- I will ask about the HLA typing of the first transplant and the cause of first graft failure.
The DSA level would be required to decide about further plan of action
ABO compatible.
1.1.2 mismatch.
Negative crossmatch.
Luminex SAB test needed if negative High risk patient for desensitization,
induction using ATG,
maintenance using triple therapy, if Positive either paired donation ,alternate donor, if
not feasible desensitization
As it is retransplant with 122 mismatch will plan induction therapy… alemtuzimab with triple immunosuppression
There is 122 mismatch
Flow cyto is negative which is good
Traditionally need a cdc to proceed to transplant
1-HLA Typing is a DNA molecules based technique and the result is mismatch 1:1:2
2-the cross match type is FCM cross match and the result is negative for B-cell and T-cell.
3-He was previously transplanted. most likely he has high cPRA.
4- 2 MISMATCH AT DR locus put him at risk for graft loss during the first 6 months. and the poor HLA matching between donor and recipient associated with poor long term graft survival.
5- the decision to proceed or not depend on the DSA presence(most likely is negative or weak as FCM is negative), the time that the patient spent on dialysis and the cPRA percentage(if it is high, he may accept this poor match as long as the FCM is negative).
6- if the donor is living, I prefer to put the recipient at a paired\pool exchange to get a better match.
This pair is Abo compatible, 8 out of 8 mismatch, sensitized patient(previous transplant ).
FCXM for T & B were negative ,so we need Solid-phase immunoassay (Luminex) , SAB with MFI .
This pair is high risk immunologically, based on the data mentioned above ,
the options for transplant are :
1- Proceed with this donor with high risk transplant , patient might need desensitization if SAB & MFI is positive .Better to search for another donor .
2- Paired exchange transplant .
What do you mean by 8 out of 8 mismatches?
Type and technique of cross match
HLA typing of donor and recipient using sequence specific oligomer (SSO) Luminex
FCM cross match between donor and recipient
Result of cross match
⦁ Donor and recipient are ABO compatible
⦁ HLA matching between Donor and recipient showed 112 mismatch
⦁ Patient has history of renal transplantation in 2002 meaning that this patient is sensitized
⦁ Cross match is negative for both T and B cell, but no detailed date about the presence of DSA
Are you happy to proceed based on the result of this cross match?
⦁ Patients has 2 HLA-DR mismatches which had worse graft survival (which is evident in the first 6 m) when compared to 0 or 1 HLA-DR mismatch, Moreover HLA DR mismatch was found to increase the risk of infection, lymphoproliferative diseases, post transplant diabetes, hypertension, hyperlipidemia and cardiovascular events, bone fractures
⦁ Patient has also HLA-DP mismatch which is not significant in the first transplant but is correlated with reduced graft survival in second transplant.
⦁ Patient is sensitized with high risk of development of denovo DSA but we should put in mind the lower like hood of getting well matched kidney.
So … It is better to find another donor but if this is difficult and patient will be waitlisted for more time so we can proceed to transplantation based on negative cross match result as a high risk transplantation, induction mandatory using ATG, maintenance using triple therapy, fu protocol. Counseling the patient regarding possible risks is mandatory.
Regarding performing DSA using Luminex to detect PLNF- Positive Luminex Negative Flow patients, no significant difference was found between patients with PLNF and those with negative cross match and negative Luminex in the incidence of AR at 1 year, graft failure at 1 and 5 years, patient survival at 1 and 5 years , Other studies showed an increase incidence of ABMR in patients with PLNC compared to those with negative Luminex
Regarding desensitization in case of PLNC, requirement and protocol is not determined till now but desensitization offer high graft survival thus it may aid in decision for desensitization.
Well done
Good to mention Anti HLA-DP
1-This Couple had compatible ABO group
2-Their HLA is 1.1.2
With negative T and B cell FCXM
3-History of previous transplant at 2002
4-No PRA result so we couldn’t be sure about non DSA antibodies as they had negative cross match.
This moderate immunological risk as we have 2 DR mismatch with history of transportation so we can use ATG as induction and maintenance therapy will be Tac,MMF and predinsilone
Yes, we need DSA level
-The mentioned scenario for ABO group matching for donor and recipient :Both of them A positive.
-HLA matching which revealed 112 At HLA -A, HLA- B and HLA -DR
-Other mismatching also at HLA C,HLA DQA1,DQB1 and DPB1
-Flowcytometry cross matching (FCXM) T and B which are all negative
-Risk stratification to take decision to proceed in transplantation and for induction and maintenance immunosuppression:
I will ask the HLA lab. to do Luminex cross match:
The low positivity cut-off of 300 MFI (mean-fluorescence intensity) is predictive of graft survival and some used the higher cut-off of 1,000 MFI.
*I do not know from where we get impression this is the second transplant??
Well done Mohamed
“There is no mismatch with his previous transplant in 2002”
See the report
This crossmatch report shows:
1) ABO compatible donor-recipient.
2) 112 HLA mismatch (but wrongly written as 122 mismatch in report)
3) Other mismatches including: HLA DQA1, DQB1, DPB1 and C
4) Both T and B cell flowcytometry crossmatch negative
5) Past history of transplantation present.
Hence this is a sensitized patient with HLA mismatches including DQ mismatch (high risk of rejection) and DP mismatch, although DSA report is not available.
Solid phase immunoassay (Luminex) should be performed. If DSA negative, the transplant can be done.
Induction with ATG, and triple drug immunosuppression (Tacrolimus, MMF and steroids) is the preferred form of immunosuppression in this patient.
Post transplant DSA monitoring and preferably protocol biopsy would be needed as a part of overall graft management.
Yes, Solid-phase immunoassay (Luminex) should be performed.
Will done
ABO compatible donor with 111 HLA mismatched, in addition to mismatching in HLA-C, HLA-DQ & HLA DP, & previous transplantation. Although FCXM is negative for both B & T cells, but the recipient considered high risk so need induction with T cells depleting agent & close monitoring OF DSA post transplantation.
122 mismatch Ban
Why is it high risk?
high risk due to one HLA-B mismatch with 2 HLA-C& HLA-DP match which carry risk of rejection in addition to history of previous transplantation that cause increase risk of alloantibodies against HLA-C Ag.
112 mismatched
also 2 HLA-DR mismatch carry high risk of rejection
Balaji my friend
We mentioned mismatches, not DSA. What do you need to stratify the risk? I did not provide all information. What would you ask the tissue typing lab to check?
The donor and recipient are ABO compatible( both have A blood group)
There are many HLA mismatches HLA A,B,DR 112 and also have 2 HLA C mismatches, 2 HLA DRB1 mismatches, 2 HLA DQA1 mismatches, 1 HLA DQB1 mismatch, and 1 HLA DPB1 mismatch.
The patient and donor had high HLA mismatch , and the patient is previously sensitized ( second renal transplant), This puts the patient at high risk of acute rejection post transplantation .
B cell and T cell flow crossmatch is negative and transplantation can be done.
Luminex SAB DSA screening should be done to identify if he had DSA even FC XM is negative since low level DSA can be present. and monitoring for those DSA is needed post transplantation.
The transplantation is high risk and need induction with ATG and triple immunosuppression (steroids , TAC,MMF), and need close monitoring post transplantation.
Thanks, Mujtaba
Well done.
-The report above demonstrates matching at ABO system, mismatch between the donor and recipient at the level of classical HLA, 112, and many mismatches at non-classical loci HLA-C, HLA-DP B1,- DQB1,-DQA1.
-HLA-DQ mismatches have been associated with an increased risk of rejection and allograft loss in kidney transplant recipients. HLA-C antibodies are also associated with the incidence of acute rejection as suggested by some studies.
-Although the flowcytometry crossmatch is negative, the level of mismatch at many loci increases the risk of rejection after transplantation.
-By definition the donor is at high risk for allograft rejection and accordingly should receive induction immunosuppression compatible with his risk.
-The recommended induction therapy is rATG and pulse steroids with maintenance with CNI based regimen, MMF and steroids.
-Patient at this high risk should be screened for de novo DSA, and should undergo protocol biopsies
Not quite right this time. What do you need to stratify the risk? I did not provide all information. What would you ask the tissue typing lab to check?
Keep trying Mohamed
Thank you Dr for your reply.
In this patient with negative FCXM, and several mismatches in the classic and non classic HLA antigens, screening for preformed antibodies is mandatory.
Screening should be done using solid phase assays to identify anti-HLA antibodies.
ABO Compatible Pair (Donor and Recipient both are ABO group A+ve )
THE OVERALL HLA-MISMATCH IS 1-1-2
There are multiple mismatches :
One mismatch at a locus in HLA-A
One mismatch at a locus in HLA-B
2 mismatches at 2 loci in HLA-C
2 mismatches at DRB1
1 mismatch at DRB4
2 mismatches at DQA1
1 mismatch at DQB1
1 mismatch at DPB1
I WILL PROCEED TO TRANSPLANTATION PROCESS:
What do you need to stratify the risk? I did not provide all information. What would you ask the tissue typing lab to check?
Keep trying Safi
ABO matched recipient and donor.
they have 112 mismatch
As both are suitable for operation , I shall proceed with the transplantation.
What do you need to stratify the risk? I did not provide all information. What would you ask the tissue typing lab to check?
Keep trying Abo Hanfi
phsiysical cross match between donor and recpient with the same blood group A.
USING FLOW CYTOMETRY CROSS MATCH TECHINIQUE .
HLA MSIMATCH BETWEEN DONOR AND RECIPENT HLA( A-B-DR )1:0:2 MISMATCHES.
YE S I AM HAPPY TO GO FOR TRANSPLANTION .
I HAVE TO ASK IS ACDEVERIC OFFER ?
IF YES IA M HAPPY TO GO FOR ATG INDUCTION?.
THER IS NOTE IN REPORT THAT THER IS MISMATCH ON HLA C -DQA1, DQB1, DPB1.
HLA-DQ mismatches are associated with acute rejection, independent of HLA-A B DR mismatches and initial immunosuppression.
HLA-C matching of all kidney donors and recipients seems to be an option to reduce the probability of acute rejection episodes
REFEENCE
https://doi.org/10.1016/j.trim.2020.101287
Kidney International (2021) 100, 1012–1022; https://doi.org/10.1016/ j.kint.2021.06.026
CJASN ePress. Published on March 31, 2016 as doi: 10.2215/CJN.11641115
Nephrol Dial Transplant 2001 Feb;16(2):355-60. doi: 10.1093/ndt/16.2.355.
SORRY THIS IS 1:1:2 MISMATCH NOT 1:0:2
Exellent Mohamed speaking of DQ ,also DP dsa can occur with a negative cross match and yet AMR can happen.This patient has a DPB1 mismatch.
YOU ARE RIGHT INDUCTION is highly indicated.
Thanks a lot
What do you need to stratify the risk? I did not provide all information. What would you ask the tissue typing lab to check?
Keep trying Mohamed
cPRA of the recpient, and if there is a DSA and how much ? Most centres have cut values for transplanting pt with dsa, some 5000, the othere 10000. It will change plane of maintinace immunosuprresion from the start and post transplant care for monitoring of dsa if present.
Sorry change induction immunosuppression protocol.
ABO compatible pair
There is 112 mismatching ( in the report 122)
Flow cytometry crossmatch is negative for both T & B cells
I will proceed transplanting this patient using ATG for induction and maintenance therapy with Tac, MMF & steroids.
I think this is the second transplant as noted from the crossmatch report, so there will be a need for DSA monitoring and I will do protocol biopsy if the patient accept.
You are right at least DSA monitoring.
What do you need to stratify the risk? I did not provide all information. What would you ask the tissue typing lab to check?
Keep trying Ibrahim
the risk can be stratified based on multiple factors including :
both T and B cell crossmatch are negative
it is written 122 mismatch, but i noticed 1 mismatch in B locus not 2
we can proceed in renal transplantation
induction ATG
maintenance tacrolimus , MMF, steroid with slow
follow up of DSA
You are right it is a112 mismatch.
Do you need to know the DSA level beforehand?
cross match report
ABO Compatible
HLA mismatch 1-1-1
Other mismatches including HLA-C, HLA DQ A1, HLA DQB1, HLA-DPB1
Both T and B cell flow cytometry cross match negative.
Would like to know Luminex SAB report of the recipient to know whether DSA is present and its MFI.
If DSA is negative in recipient(Luminex SAB report needed) will go ahead with basiliximab induction
If DSA is positive but MFI<1000- will go ahead with ATG induction.
If DSA is positive and MFI 1000-10000- desensitize the recipient by doing plasmapheresis plus low dose ivig plus ATG
If DSA is positive and MFI>10000 or multiple DSA with >5000-avoid