14th International HLA and Immunogenetics Workshop: Report on the Prospective Chronic Rejection Project

Abstract

An international collaborative study of 45 transplant centers was undertaken at the 14th International HLA (human leukocyte antigen) and Immunogenetics Workshop to see if HLA antibodies detected posttransplant are predictive of chronic graft failure. With the newly developed assay, MICA (major histocompatibility complex class I-related chain A) antibodies were also measured and their effect analyzed. Total of 5219 sera from patients who were more than 6 months posttransplant with functioning graft were tested for HLA antibodies by enzyme-linked immunosorbent assay, flow cytometry, or Luminex. HLA antibodies were found in 27.2% of kidney patients, 23.6% in the liver, 52.7% in the heart, and 21.7% in the lung. The method of antibody testing did not have a marked influence on the frequency of antibodies detected. MICA antibodies were detected in 15% of kidney patients, 30% of heart patients, and 31% of liver patients. Among 948 kidney patients who had HLA antibodies, 7.3% had rejected their graft within 1 year of testing, compared with 1.7% in 2615 patients without HLA antibodies (P= 0.8 x 10(-17)). Death occurred in 1.4% of total kidney patients and did not correlate to the presence of antibodies. We conclude that patients with posttransplant HLA antibodies indeed have a higher rate of chronic graft failure and that posttransplant antibodies are predictive of chronic rejection.

Donor-specific antibodies are associated with antibody-mediated rejection, acute cellular rejection, bronchiolitis obliterans syndrome, and cystic fibrosis after lung transplantation

“…A consensus workshop found that non-DSA HLA antibodies with a strong signal had an association with graft failure across solid-organ transplantation. 36 Possible mechanisms include cross-reactivity with the major proteins A B C OR DR/DQ/DP, mismatches at the allele level, and polymorphic epitopes with multiple targets. This raises awareness for whether non-DSA HLA antibodies require therapy.…”

Effector Mechanisms of Rejection

“…One of the independent risk factors for the development of chronic rejection is the presence of anti-HLA class I and especially class II antibodies (Ozawa et al 2007). More than 80% of patients with transplant glomerulopathy have anti-HLA antibodies, 85% being directed against class I or class II antigens (Gloor et al 2007;Sis et al 2007;Issa et al 2008).…”

Development of a cross-platform biomarker signature to detect renal transplant tolerance in humans

“…Screening was performed as previously described (33). After washing, HLA-coated Luminex screening beads and 12.5 μl of patient serum or control serum were added on a plate and mixed gently for 30 minutes in the dark.…”