Accelerated humoral renal allograft rejection due to HLA-C14 mediated allosensitization to HLA-Bw6

Persaud, Stephen P.; Duffy, Brian; Phelan, D.; Mohanakumar, Thalachallour; Santos, Rowena Delos; Gaut, Joseph P.; Liu, Chang

doi:10.1016/j.humimm.2017.09.004

Cited by 6 publications

(5 citation statements)

References 27 publications

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“…Although most reports lack analysis of antibody generation to immunogenic public epitopes of HLA-C antigens, Persaud et al [6] presented the case of an accelerated acute humoral response due to a C14 antigen bearing a Bw6 epitope at position 80NRG, which the patient was previously sensitized to through pregnancy. In our patient's case, the antibody to HLA-C7 generated to the 76VRN public epitope, is shared by several HLA-C as well as HLA-B antigens; however, this epitope is different from the Bw6 public epitope-associated antibody described by Persaud et al [6]. As in our case, the Bw6 is considered a self-epitope due to the patient's B35 antigen.…”

Section: Discussionmentioning

confidence: 99%

“…DSA are detected in most cases of ABMR in which diffuse peritubular capillaries (PTC) C4d is positive [1,2]. Although HLA-C matching is not taken into consideration when assessing histocompatibility and matching in kidney transplantation due to the close linkage disequilibrium with HLA-B antigens as well as its low expression level, recent reports have shown that antibodies targeted towards preexisting immunogenic epitope of HLA-C antibodies are associated with allograft rejection and graft failure [3,4,5,6]. In this context, we present a patient with biopsy features of ABMR, who on further testing showed strong DSA to an immunogenic epitope of HLA-C7.…”

Section: Introductionmentioning

confidence: 99%

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A curious case of de novo anti-HLA-C antibody-mediated humoral rejection and Fabry-like zebra bodies in a renal transplant recipient

Abuzeineh

Ziadeh

Kheradmand³

et al. 2020

CNCS

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Detection of donor-specific antibodies (DSA) is an essential part of diagnosing antibody-mediated renal allograft rejection (ABMR). The role of solitary preformed, or post-transplant HLA-C antigens in solid organ transplantation is unclear, due to the less sensitive nature of the historical assays, lack of data, low expression level on the cell surface, and their coexistence with other anti-HLA DSA. Herein, we present the case of a 39-year-old African American man, without prior history of pre-transplant sensitization that was diagnosed with biopsyproven ABMR due to de novo donor-specific anti-HLA-C antibodies. This case report illustrates the role of HLA-C antibodies in causing ABMR if generated toward immunogenic-shared epitopes and demonstrates the need for their recognition in the pre-and post-transplant period. Another interesting aspect of this case is the incidental finding of Fabry-like zebra bodies, which we eventually determined to be of unclear etiology.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A curious case of de novo anti-HLA-C antibody-mediated humoral rejection and Fabry-like zebra bodies in a renal transplant recipient

Abuzeineh

Ziadeh

Kheradmand³

et al. 2020

CNCS

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“…Additionally, the patient also appeared to have DSA to Bw6, an antigen shared with many B locus antigens ( 11 ), with an average MFI ~10,000 ( Figure 1C ). This was particularly concerning as even low level anti-Bw6 antibodies can lead to allograft rejection ( 12 ). However, due to the patient’s rapidly declining clinical status, the offer was accepted and heart followed by kidney transplantation following the DUET protocol was performed ( 7 ).…”

Section: Case Presentationmentioning

confidence: 99%

Case report: Successful simultaneous heart-kidney transplantation across a positive complement-dependent cytotoxic crossmatch

Yamamoto

Pearson²,

Ababneh³

et al. 2022

Front. Nephrol.

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Preformed donor-specific antibodies are associated with a higher risk of rejection and worse graft survival in organ transplantation. However, in heart transplantation, the risk and benefit balance between high mortality on the waiting list and graft survival may allow the acceptance of higher immunologic risk donors in broadly sensitized recipients. Transplanting donor-recipient pairs with a positive complement dependent cytotoxic (CDC) crossmatch carries the highest risk of hyperacute rejection and immediate graft loss and is usually avoided in kidney transplantation. Herein we report the first successful simultaneous heart-kidney transplant with a T- and B-cell CDC crossmatch positive donor using a combination of rituximab, intravenous immunoglobulin, plasmapheresis, bortezomib and rabbit anti-thymocyte globulin induction followed by eculizumab therapy for two months post-transplant. In the year following transplantation, both allografts maintained stable graft function (all echocardiographic left ventricular ejection fractions ≥ 65%, eGFR>60) and showed no histologic evidence of antibody-mediated rejection. In addition, the patient has not developed any severe infections including cytomegalovirus or BK virus infection. In conclusion, a multitarget immunosuppressive regimen can allow for combined heart/kidney transplantation across positive CDC crossmatches without evidence of antibody-mediated rejection or significant infection. Longer follow-up will be needed to further support this conclusion.

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“…27,28 The HLA-C locus being polymorphic, 29,30 dozens of eplets were described for HLA-C alleles and antigens, either locus specific or shared with HLA-A or -B antigens. 25,31,32 Anti-HLA-C antibodies are found in approximately 10% to 15% of patients on SOT waiting lists. Nevertheless, their prevalence in the HLA-sensitized population is lower than for HLA-A and -B antibodies, being present in about half of them vs around 80% for other class I antibodies, 26,[33][34][35][36] and they are rarely isolated.…”

Section: Hla-c Immunogenicity and Antibodies Directed At Hla-cmentioning

confidence: 99%

“…HLA‐C antigens are undoubtedly immunogenic as they can induce the formation of allo‐antibodies secondary to transfusions, pregnancies or transplantations 25,26 . Indeed, anti‐HLA antibodies recognize amino acid modifications on surface accessible positions of HLA molecules, named by Duquesnoy et al as “eplets.” 27,28 The HLA‐C locus being polymorphic, 29,30 dozens of eplets were described for HLA‐C alleles and antigens, either locus specific or shared with HLA‐A or ‐B antigens 25,31,32 …”

Section: Hla‐c Immunogenicity and Antibodies Directed At Hla‐cmentioning

confidence: 99%

Clinical relevance of donor‐specific antibodies directed at HLA‐C: A long road to acceptance

Visentin

Couzi

Taupin

2020

HLA

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In solid organ transplantation (SOT), the clinical relevance of donor-specific antibodies (DSA) directed at anti-HLA-A,-B,-DR and-DQ antigens is largely recognized while it is still a matter of debate for DSA directed at HLA-C. In this review, we summarize the peculiarities of HLA-C among class I HLA antigens as well as their immunogenicity, which underlie the clinical relevance of HLA-C locus and anti-HLA-C DSA in SOT. Many factors, both intrinsic and extrinsic to the HLA-C gene and HLA-C protein, explain its lower expression in comparison with HLA-A and-B. This lower expression can explain the apparent lower immunogenicity of HLA-C leading to a lower prevalence and strength of anti-HLA-C antibodies. Nevertheless, HLA-C antigens are truly immunogenic and preformed anti-HLA-C DSA are clinically relevant. Indeed, anti-HLA-C DSA are able to bind donor cells and to activate the complement pathway both ex vivo and in vivo. In line with this, numerous clinical studies now show that preformed DSA directed at native HLA-C molecules induce poorer graft outcomes. We then plead for the inclusion of HLA-C in all transplant allocation systems and we propose a strategy to cope with anti-HLA-C DSA in SOT. Beyond SOT, anti-HLA-C antibodies generate a growing interest in the allo-HCT, transfusion and obstetrics fields, while new concepts such as the role of the "missing-self" in solid organ rejection places HLA-C as an inescapable actor in transplant tolerance.

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Accelerated humoral renal allograft rejection due to HLA-C14 mediated allosensitization to HLA-Bw6

Cited by 6 publications

References 27 publications

A curious case of de novo anti-HLA-C antibody-mediated humoral rejection and Fabry-like zebra bodies in a renal transplant recipient

A curious case of de novo anti-HLA-C antibody-mediated humoral rejection and Fabry-like zebra bodies in a renal transplant recipient

Case report: Successful simultaneous heart-kidney transplantation across a positive complement-dependent cytotoxic crossmatch

Clinical relevance of donor‐specific antibodies directed at HLA‐C: A long road to acceptance

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