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 Table of Contents  
CASE REPORT
Year : 2021  |  Volume : 6  |  Issue : 1  |  Page : 100-102

HLA class II positivity by lysate crossmatch in renal transplant scenario-dangerous if ignored!!!


1 Department of Transfusion Medicine and Histocomptibility and Immunogenetics, Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Mumbai, Maharashtra, India
2 Department of Histocomptibility and Immunogenetics, Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Mumbai, Maharashtra, India

Date of Submission10-Mar-2021
Date of Decision05-May-2021
Date of Acceptance05-May-2021
Date of Web Publication29-May-2021

Correspondence Address:
Dr. Rajesh B Sawant
Department of Transfusion Medicine and Histocomptibility and Immunogenetics, Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/gjtm.gjtm_22_21

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  Abstract 


The detection of antibodies before transplantation is an important step in assessment of patient immunological risk and exclusion of incompatible donors. Many centers have now implemented donor-specific antibody (DSA) along with complement-dependent cytotoxicity crossmatch (CDC XM) for renal transplant cases. A 34-year-old male with end-stage kidney disease was referred for an ABO-compatible transplant from his mother. The CDC XM done 30 days before transplant was negative. DSA XM was negative for Class I (median fluorescence intensity [MFI] 189) and positive for Class II (MFI 1671). Since CDC and DSA Class I were negative, the nephrologists went ahead with the transplantation. On day 6 posttransplant, serum creatinine showed a rising trend (up to 2.13 mg/dl), and therefore, renal biopsy was done which showed mild acute tubular necrosis with positive C4d staining. DSA XM performed on day 15 posttransplant showed negative Class I (MFI 148) and positive Class II (MFI 9987) confirming antibody-mediated rejection (AMR). The patient was started on steroids, and intravenous immunoglobulin and serial plasma exchanges were performed. Then, DSA Class II levels came down to 1602. DSA levels have been monitored periodically and Class II MFI values have been ranging from 2000 to 4000. The patient is maintained on routine immunosuppression, and a graft is intact with serum creatinine level between 1.7 and 1.8 mg/dl 8 months posttransplant. DSA-isolated Class II positivity in renal transplant recipients correlates strongly with AMR and should be considered clinically significant.

Keywords: Complement-dependent cytotoxicity, creatinine, donor-specific antibody, positive, renal transplantation


How to cite this article:
Sawant RB, Mehta P, Naker D. HLA class II positivity by lysate crossmatch in renal transplant scenario-dangerous if ignored!!!. Glob J Transfus Med 2021;6:100-2

How to cite this URL:
Sawant RB, Mehta P, Naker D. HLA class II positivity by lysate crossmatch in renal transplant scenario-dangerous if ignored!!!. Glob J Transfus Med [serial online] 2021 [cited 2021 Dec 7];6:100-2. Available from: https://www.gjtmonline.com/text.asp?2021/6/1/100/317126




  Introduction Top


Chronic kidney disease and its progression to end-stage renal disease (ESRD) is a major global health problem. Dialysis is used as a treatment for patients with ESRD and is found to be effective to ease the symptoms. However, dialysis therapy is often experienced as a burden, and mortality and morbidity in patients on dialysis is high.[1] Renal transplantation is the only treatment resulting in significant prolongation of patient survival. Therefore, it is the preferred treatment in most patients with ESRD.

Human leukocyte antigen (HLA) typing, antibody screening, and crossmatching have become an integral part of the pretransplant work-up and posttransplant monitoring phases of renal transplantation. The results of these tests help in guiding the treatment plan, transplant timing, management protocols, and desensitization plan of the recipient. Over the years, these tests have gradually evolved and have now found a permanent place in the transplantation work-up protocol in some form or the other, depending on the respective institutional policies.

Although single-antigen bead assay is a state-of-art technique for detection and identification of HLA antibodies, in resource-limited facilities, lysate crossmatch (XM) in conjunction with complement-dependent cytotoxicity XM (CDC XM) is being performed for better risk assessment in renal transplantation in Indian subcontinent. CDC XM being the gold standard technique is considered for ultimate decision making for renal transplantation at our centre. The Lysate XM is used as a supplementary screening technique and results are correlated with the CDC XM results. lysate XM is used as a supplementary screening technique to confirm the CDC XM results. The lysate XM is performed using commercially available reagent kit on Luminex platform. The XM procedure involves coating the fluorescent beads with antibodies specific for HLA Class I or II. When treated with donor lysate preparation, these beads will capture the respective HLA antigens of the donor and serve as an HLA target for the detection of donor-specific antibodies (DSAs). This is a semi-quantitative test which identifies the presence, the relative strength, and the specificity of HLA antibodies. Lysate XM has a number of advantages over CDC XM for the detection of antibodies; most notably, it is independent of living cells.

Lysate XM is more specific in demonstrating the HLA compatibility while CDC XM involves HLA and non-HLA specificities too. Solid-phase immunoassay is more sensitive for detection of weakly reactive HLA antibodies as compared to CDC XM; therefore, both tests can be used in combination for pre- and posttransplant management.

The detection of antibodies before transplantation is an important step in assessment of patient immunological risk and exclusion of incompatible donors. Many centers have now implemented lysate XM along with CDC XM for renal transplant cases.


  Case Report Top


A 34-year-old Asian male with ESRD due to chronic tubulointerstitial disease was referred for renal transplant. His mother was preferred as a potential kidney donor with 3/6 HLA matching status. It was an ABO-compatible transplantation. The baseline CDC XM done 30 days before transplant was negative whereas lysate XM was negative for Class I (median fluorescence intensity [MFI] 189) but positive for Class II (MFI 1671). Since CDC and lysate XM Class I were negative and Class II being mild/weak positive, the nephrologists went ahead with the transplantation. On day 6 posttransplant, serum creatinine showed a rising trend (up to 2.13 mg/dl); therefore, renal biopsy was done which showed mild acute tubular necrosis with positive C4d staining suggesting antibody-mediated rejection (AMR).

As per our institutional protocol, lysate XM for posttransplant monitoring was performed on day +15. The results were negative for Class I (MFI 148) and positive Class II (MFI 9987) with an 80% rise in MFI values, confirming AMR. Desensitization protocol was initiated using steroids, intravenous immunoglobulin, and serial plasma exchanges. To confirm the efficacy, lysate XM was performed at regular intervals which showed a reduction in MFI values for Class II to 1602, i.e., 80%. DSA levels were constantly monitored which were consistent for HLA Class II antibodies. The patient is maintained on routine immunosuppression with constant monitoring of serum creatinine levels. The patient investigation reports and creatinine levels are outlined in [Table 1] with the reference range given in [Table 2].
Table 1: Outline of patient investigations and creatinine levels

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Table 2: Lysate crossmatch median fluorescence intensity - interpretation table

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DSA levels have been monitored periodically, and Class II MFI values have been ranging from 2000 to 4000. The patient is maintained on routine immunosuppression, and a graft is intact with serum creatinine level maximum up to 1.9 mg/dl, 8 months posttransplant.


  Discussion Top


The clinical relevance of low levels of DSA is still debated even though the presence of pretransplant DSA has generally been considered to be a risk factor for AMR and graft loss.[2] Issa et al.[3] reported in their study that the risk of developing transplant glomerulopathy and the presence of C4d in peritubular capillaries is related to higher levels of Class II DSA in patients with negative T-cell cytotoxicity (antihuman globulin) XM. The risk of AMR is associated in patients with high levels of DSA both before and after desensitization therapy.[4] Poor long-term graft survival is associated with very high levels of baseline DSA.[5]

The assessment of separate classes of DSA is of interest because of differences in HLA antigen expression in the donor's kidney. The presence of HLA Class II DSA in patients with negative T-cell XM was associated with the occurrence of AMR or poor graft survival.[1] Slavcev et al.[6] suggest that anti-HLA Class II antibodies represent a risk factor for the development of acute immunological complications during the 1st year after transplantation. Fidler et al.[7] observed a significant decrease in graft survival in a patient with solely DSA Class II positivity. Anti-HLA Class II DSA positivity in the absence of a positive CDC XM can predict early rejection of renal allograft. In the present case, pretransplant DSA Class II positivity is associated with occurrence of AMR. Although it was considered insignificant due to negative CDC XM, AMR was observed within few days posttransplant with demonstrable C4d deposition in peritubular capillaries and highly positive DSA Class II with MFI of 9987. However, with consistent desensitization protocol and therapy, the Class II DSA was reduced but is still not eliminated. Thus, we found DSA Class II to be an early predictor of renal graft failure, which could be managed with proper algorithm for monitoring DSA level before transplant. Serial monitoring of DSA is more valuable than single-point testing, particularly in the posttransplant setting, and is crucial in optimizing patient outcomes.


  Conclusion Top


DSA Class II positivity in renal transplant recipients correlated with AMR in our case and hence could be considered clinically significant. We have now implemented postrenal transplant monitoring of recipients for the presence of DSAs. Choosing a monitoring frequency based on a patient's individual risk of developing AMR posttransplant will be the most efficient and clinically relevant strategy.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Uffing A, Hidalgo LG, McMullan C, Perry J, Milford EL, Murakami N, et al. Preformed donor-specific antibodies against HLA Class II and graft outcomes in deceased-donor kidney transplantation. Transplant Direct 2019;5:e446.  Back to cited text no. 1
    
2.
Aubert V, Venetz JP, Pantaleo G, Pascual M. Low levels of human leukocyte antigen donor-specific antibodies detected by solid phase assay before transplantation are frequently clinically irrelevant. Hum Immunol 2009;70:580-3.  Back to cited text no. 2
    
3.
Issa N, Cosio FG, Gloor JM, Sethi S, Dean PG, Moore SB, et al. Trans-plant glomerulopathy: Risk and prognosis related to anti-human leuko-cyte antigen Class II antibody levels. Transplantation 2008;86:681-5.  Back to cited text no. 3
    
4.
Reinsmoen NL, Lai CH, Vo A, Cao K, Ong G, Naim M, et al. Acceptable donor-specific antibody levels allowing for successful deceased and living donor kidney transplantation after desensitization therapy. Transplantation 2008;86:820-5.  Back to cited text no. 4
    
5.
Gloor JM, Winters JL, Cornell LD, Fix LA, DeGoey SR, Knauer RM, et al. Baseline donor-specific antibody levels and outcomes in positive crossmatch kidney transplantation. Am J Transplant 2010;10:582-9.  Back to cited text no. 5
    
6.
Slavcev A, Lacha J, Sajdlova H, Vitko S, Valhova S, Striz I, et al. Antibodies to HLA class II antigens as a risk factor for acute rejection of the allogeneic kindey. Ann Transplant 2004;9:44-7.  Back to cited text no. 6
    
7.
Fidler SJ, Irish AB, Lim W, Ferrari P, Witt CS, Christiansen FT. Pre-transplant donor specific anti-HLA antibody is associated with antibody-mediated rejection, progressive graft dysfunction and patient death. Transpl Immunol 2013;28:148-53.  Back to cited text no. 7
    



 
 
    Tables

  [Table 1], [Table 2]



 

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