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Major histocompatibility complex class I-related chain A allele mismatching, antibodies, and rejection in renal transplantation.

Abstract：

:Even when kidney allografts are well matched for human leukocyte antigen (HLA) and anti-HLA antibodies are not detected, graft rejection can still occur. There is evidence that some patients who lose their graft have antibodies specific for major histocompatibility complex (MHC) class I-related chain A (MICA) antigens. We investigated whether mismatching MICA alleles associates with MICA antibody production and graft rejection or dysfunction. MICA and HLA antibody screening in 442 recipients was performed, and specificities were confirmed in a subgroup of 227 recipients using single-antigen multiplex technology. For assignment of MICA antibody specificity, we used three independent assays. In addition, MICA alleles of 227 recipients and donors were determined by DNA sequencing. In all, 17 patients (7.5%) had MICA antibodies, and 13 patients (6%) developed MICA donor-specific antibodies (DSA). Multivariate analysis revealed MICA mismatching, as an independent significant factor associated with the presence of MICA antibodies (p = 0.009), and 14 mismatched MICA residues significantly correlated with MICA antibody production. MICA and HLA antibodies significantly associated with acute rejection (AR) and MICA DSA and HLA DSA correlated with decreased graft function by univariate and multivariate analysis. We conclude that mismatching for MICA epitopes in renal transplantation is a mechanism leading to production of MICA antibodies that associate with AR and graft dysfunction.

journal_name

Hum Immunol

journal_title

Human immunology

authors

Cox ST,Stephens HA,Fernando R,Karasu A,Harber M,Howie AJ,Powis S,Zou Y,Stastny P,Madrigal JA,Little AM

doi

10.1016/j.humimm.2011.05.004

subject

Has Abstract

pub_date

2011-10-01 00:00:00

pages

827-34

issue

10

eissn

0198-8859

issn

1879-1166

pii

S0198-8859(11)00111-X

journal_volume

72

pub_type

杂志文章

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