Antibodies against MICA Antigens and Kidney-Transplant Rejection

Zou, Yizhou; Šťastný, Peter; Süsal, Caner; Döhler, Bernd; Opelz, Gerhard

doi:10.1056/nejmoa067160

Cited by 394 publications

(302 citation statements)

References 29 publications

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“…DSA is frequent in renal transplant populations (32) but can be ''false negative'' due to incomplete coverage, unknown donor antigens, or excessively high test cutoffs, or ''false positive'' in stable patients, and can change as technology evolves. The significance of DSA against nonclassic HLA products and non-HLA products such as MHC class I polypeptide-related sequence A is controversial (33). Banff guidelines permit autoantibodies to be considered DSA, but autoantibodies are common in chronic illnesses and their causal relationship to ABMR phenotypes is unknown (34).…”

Section: Discussionmentioning

confidence: 99%

Identifying Subphenotypes of Antibody-Mediated Rejection in Kidney Transplants

Halloran

Lopez

Pereira

2016

American Journal of Transplantation

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The key lesions in antibody-mediated kidney transplant rejection (ABMR) are microcirculation inflammation (peritubular capillaritis and/or glomerulitis lesions, abbreviated ''pg'') and glomerular double contours (cg lesions). We used these features to explore subphenotypes in 164 indication biopsies with ABMR-related diagnoses: 137 ABMR (109 pure and 28 mixed with T cellmediated rejection [TCMR]) and 27 transplant glomerulopathy (TG), identified from prospective multicenter studies. The lesions indicated three ABMR subphenotypes: pgABMR, cgABMR, and pgcgABMR. Principal component analysis confirmed these subphenotypes and showed that TG can be reclassified as pgcgABMR (n ¼ 17) or cgABMR (n ¼ 10). ABMR-related biopsies included 45 pgABMR, 90 pgcgABMR, and 25 cgABMR, with four unclassifiable. Dominating all time intervals was the subphenotype pgcgABMR. The pgABMR subphenotype presented earliest (median <2 years), frequently mixed with TCMR, and was most associated with nonadherence. The cgABMR subphenotype presented late (median 9 years). Subphenotypes differed in their molecular changes, with pgABMR having the most histologic-molecular discrepancies (i.e. potential errors). Donor-specific antibody (DSA) was not identified in 29% of pgcgABMR and 46% of cgABMR, but failure rates and molecular findings were similar to cases where DSA was known to be positive. Thus, ABMR presents distinct subphenotypes, early pg-dominant, late cg-dominant, and combined pgcg phenotype, differing in time, molecular features, accompanying TCMR, HLA antibody, and probability of nonadherence.

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Section: Discussionmentioning

confidence: 99%

Identifying Subphenotypes of Antibody-Mediated Rejection in Kidney Transplants

Halloran

Lopez

Pereira

2016

American Journal of Transplantation

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“…Independently, non-HLA antibodies have been demonstrated to play a major role in the pathogenesis of antibody-mediated rejection [32][33][34][35]. In particular, non-HLA antibodies against endothelial antigens such as the major histocompatibility complex class I-related chain A (MICA) cause antibody-mediated rejection in transplantation patients [36,37]. Moreover, anti-endothelial cell antibodies against other known endothelial surface antigens such as the angiotensin II type 1-receptor, vimentin and collagen V or against unknown antigens have been implicated in antibodymediated rejection after kidney transplantation [32,34].…”

Section: Detection Of Hla Antibodiesmentioning

confidence: 99%

Acute and chronic antibody-mediated rejection in pediatric kidney transplantation

et al. 2014

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Acute antibody-mediated rejection is a diagnostic challenge in renal transplantation medicine. However, it is an important diagnosis to make, since chronic antibody-mediated rejection (CAMR) is the main cause of long-term graft loss. Antibody-mediated rejection is diagnosed by detecting donorspecific antibodies (DSAs) in the blood in combination with observing typical histomorphological signs in kidney biopsy, as described in the Banff classification. Therapy is based on the removal of DSAs by administering intravenous immunoglobulins (IVIGs), plasmapheresis, or immunoadsorption. Reoccurrence of antibodies is diminished by the use of rituximab, increased immunosuppression, and in some cases additional experimental substances. A combination of these techniques has been shown to be successful in the majority of cases of acute and chronic antibody-mediated rejection. Routine DSA monitoring is warranted for early detection of antibody-mediated rejection.

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“…In solid organ recipients (8)(9)(10)(11) and dialysis patients (12), the overall rate of seroconversion to the seasonal flu vaccine is in the range of 30% to 50%. The use of adjuvanted vaccine has raised concerns for immunocompromised patients, because of possible induction of allo-immune responses, such as anti-human histocompatibility leukocyte antigen (HLA) antibodies (Abs) or MHC class I-related chain A (MICA) Abs (13)(14)(15)(16). Indeed, the AS03 adjuvant present in some vaccines promotes immunogenicity by modulating the expression of local cytokines and by increasing the antigen loading in monocytes (17).…”

Section: Introductionmentioning

confidence: 99%

Influenza A/H1N1 Vaccine in Patients Treated by Kidney Transplant or Dialysis

Broeders

Hombrouck²,

Lemy³

et al. 2011

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives In 2009, the pandemic influenza A/H1N1 accounted for worldwide recommendations about vaccination. There are few data concerning the immunogenicity or the security of the adjuvanted-A/H1N1 vaccine in transplanted and hemodialyzed patients.Design, setting, participants, & measurements Sera from 21 controls, 53 hemodialyzed (HD) patients, and 111 renal transplant recipients (RT) were sampled before (T0) and 1 month after (T1) a single dose of Pandemrix® vaccine (GSK Biologicals, AS03-adjuvanted). We measured the neutralizing antibodies against A/H1N1/2009, the geometric mean (GM) titers, the GM titer ratios (T1/T0) with 95% confidence intervals, and the seroconversion rate (responders: Ն4-fold increase in titer). The HLA and MICA immunization was determined by Luminex technology. ResultsThe GM titer ratio was 38 (19 to 78), 9 (5 to 16), and 5 (3 to 6) for controls, HD patients, and RT patients, respectively (P Ͻ 0.001). The proportion of responders was 90%, 57%, and 44%, respectively (P Ͻ 0.001). In RT patients, the prevalence of histocompatibility leukocyte antigen (HLA) class I, histocompatibility leukocyte antigen class II, and MHC class I-related chain A immunization, was, respectively, 15%, 14%, and 14% before and 14%, 14%, and 11% after vaccination (P ϭ 1, 1, and 0.39). ConclusionsThe influenza A/H1N1-adjuvanted vaccine is of limited efficacy but is safe in renal disease populations. The humoral response is lower in transplanted versus hemodialyzed patients. Further studies are needed to improve the efficacy of vaccination in those populations.

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Antibodies against MICA Antigens and Kidney-Transplant Rejection

Abstract: Presensitization of kidney-transplant recipients against MICA antigens is associated with an increased frequency of graft loss and might contribute to allograft loss among recipients who are well matched for HLA.

Cited by 394 publications

References 29 publications

Identifying Subphenotypes of Antibody-Mediated Rejection in Kidney Transplants

Identifying Subphenotypes of Antibody-Mediated Rejection in Kidney Transplants

Acute and chronic antibody-mediated rejection in pediatric kidney transplantation

Influenza A/H1N1 Vaccine in Patients Treated by Kidney Transplant or Dialysis

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