Kidney transplantation in a recipient with anti-HLA antibody IgM positive

Preformed donor-specific antibodies against human leukocyte antigen can induce antibody-mediated rejection after organ transplant. Hence, future transplant recipients undergo pretransplant screening for preformed antibodies (ie, virtual crossmatch). Subsequently, prospective (analytic) crossmatching is performed using conventional, complementdependent cytotoxicity assays and/or flow cytometrybased methods. The present article reviews factors that must be considered when unexpected, positive, prospective crossmatches are observed. First, the prozone effect caused by the interference of complement or immunoglobulin M must be abrogated by treating the serum with moderate heat, dilution, hypotonic dialysis, EDTA, or dithiothreitol. Second, the physician must check for the presence of potentially interfering autoantibodies (in a context of autoimmune disease or human immunodeficiency virus infection) or therapeutic antibodies (such as rituximab and antithymocyte globulin). In conclusion, knowledge of each assay's technical characteristics will enable the physician to reliably interpret any discrepancies. The reasons for an unexpected, positive, prospective crossmatch must be elucidated before transplant to ensure efficient organ allocation and optimize patient outcomes.

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“…This may demonstrate that the positive CDC-XM was due to the presence of anti-HLA IgM antibodies against one of the donor-specific antigens. 21 …”

Section: False-negative Bead Assay Resultsmentioning

confidence: 99%

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Desoutter

Apithy²,

Guillaume³

2017

Exp Clin Transplant

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“…While most centres believe that the presence of an IgG antibody is contraindication for the graft success, the role of IgM antibodies has not been universally agreed upon. As per experience of several transplant centres, the presence of these antibodies is irrelevant; however, a few case reports highlight a negative influence of IgM antibodies on graft outcome (Khan et al ., ; Suzuki et al ., ). Stastny et al .…”

Section: Tools For Detection Of Antibodiesmentioning

confidence: 97%

Clinical and immunological relevance of antibodies in solid organ transplantation

Mehra

Baranwal

2016

Int J Immunogenetics

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The two important issues affecting recipients of solid organ transplants and of importance to immunologists are (i) sensitization of the recipient to HLA antigens and the resultant humoral immune response leading to the development of anti-HLA antibodies; and ii) development of robust assays for early detection of humoral rejection post-transplant. Evidence from several studies clearly indicates that presence of circulating anti-HLA antibodies especially donor specific leads to early graft loss and high titres of DSA may even lead to hyperacute or accelerated acute rejection. Long-term graft survival too is adversely affected by the presence of either pre- or post-transplant DSA. HLA matching status of the recipient - donor pair - is an important factor in the modulation of humoral response following transplantation and in a way affects de novo development of DSA. Data collected over the past decade clearly indicate significantly lower level of DSAs in optimally matched donor-recipient pairs. HLA mismatches especially those on HLA-DR and HLA-C loci have wider implications on post-transplant graft survival. The presence of circulating anti-HLA antibodies leads to endothelial damage in the newly grafted organ through complement dependent or independent pathways. Although detection of C4d deposition in renal biopsies serves as an important indicator of humoral rejection, its absence does not preclude the presence of DSAs and humoral rejection, and hence, it cannot be relied upon in every case. The emergence of epitope-based screening for anti-HLA antibodies on Luminex platform with high degree of sensitivity has revolutionized the screening for anti-HLA antibodies and DSAs. Studies indicate that humoral response to non-HLA antigens might also have a detrimental effect on allograft survival. High titres of such circulating antibodies may even lead to hyperacute rejection. Pre-emptive testing of solid organ recipients, especially kidney transplant recipients for anti-HLA and non-HLA antibodies and aggressive post-transplant monitoring of allograft function to detect DSAs using Luminex-based tests, is highly recommended.

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“…Other classes of antibodies particularly IgM, despite being strongly complement-fixing, is not considered harmful [61][62][63]. However, recent case reports and small case series suggest they may modulate immune responses and are associated with rejection [64][65][66] and hence IgM class of HLA-specific antibodies warrants a detailed study, especially in relation to long term outcomes rather than simply AAMR.…”

Section: Class and Subclass Switchingmentioning

confidence: 99%

Defining Clinically Pathogenic HLA-Specific Antibodies - Granular Details in Characteristics in Pre and Early Time Following HLA-Antibody Incompatible Kidney Transplantation

Babu¹,

Khovanova²,

Higgins³

2021

obm transplant

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Antibodies against donor HLA determine access to solid organ transplantation and in many cases the outcome of transplantation, but graft failure is not an inevitable consequence of their presence. Much research has been performed with two main aims – which antibodies represent the highest risk factor prior to transplantation, and second to understand how donor specific HLA antibodies behave after transplantation, with a long-term aim of being able to manipulate their production. HLA antibody incompatible kidney transplantation is the best model for examining antibody responses and this review looks at methods for interrogating the antibodies using ‘traditional’ snapshot techniques such as cytoxicity testing, and newer dissection techniques such as antibody subclass, complement binding and activity and affinity. Integral to the understanding of the large datasets generated is sophisticated mathematical analysis using techniques such as decision tree analysis and unsupervised machine learning. This review examines key aspects of this work, performed by us and others.

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Kidney transplantation in a recipient with anti-HLA antibody IgM positive

Cited by 9 publications

References 15 publications

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Clinical and immunological relevance of antibodies in solid organ transplantation

Defining Clinically Pathogenic HLA-Specific Antibodies - Granular Details in Characteristics in Pre and Early Time Following HLA-Antibody Incompatible Kidney Transplantation

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