Donor-specific antibodies to human leukocyte antigens are associated with and precede antibodies to major histocompatibility complex class I-related chain A in antibody-mediated rejection and cardiac allograft vasculopathy after human cardiac transplantation

Humoral immune responses to mismatched donor human leukocyte antigen (HLA) and major histocompatibility complex (MHC) class I-related chain A (MICA) have been reported to contribute to immunopathogenes's of antibody-mediated rejection (AMR) in the early period and cardiac allograft vasculopathy (CAV) in the late period after cardiac transplantation (HTx) The goal of this study is to define the roles of donor-specific antibodies (DSA) and anti-MICA in AMR and CAV A total of 95 post-HTx recipients were enrolled 43 patients in the early period (<= 12 months post-HTx) and 52 patients in the late period (>12 months post-HTx) Development of DSA and anti-MICA were serially monitored using Luminex Development of DSA (AMR+ n = 6/8 75% AMR- n = 4/35 11% p = 0 009) and anti-MICA (AMR+ n = 5/8 63% AMR- n = 4/35 11% p = 0 002) was significantly associated with AMR AMR+DSA+ patients demonstrated increased anti-MICA levels compared with AMR+DSA- patients (p=0 01) Serial monitoring revealed DSA (2 7 +/- 1 4 months) preceded development of anti-MICA (6 5 2 1 months) in recipients diagnosed with AMR at 83 +/- 2 5 months post-HTx Development of DSA (CAV+ n = 8/12 67% CAV- n = 5/40 13% p = 0 004) and anti-MICA (CAV+ n = 9/12 75% CAV- n = 5/40 13% p = 0 001) was significantly associated with CAV CAV+DSA+ patients demonstrated Increased anti-MICA levels compared with CAV+DSA- patients (p = 0 01) Antibodies to HLA are associated with and precede development of anti-MICA in AMR and CAV Therefore DSA and anti-MICA can be used as noninvasive markers for monitoring AMR and CAV 2010 American Society for Histocompatibility and Immunogenetics Published by Elsevier Inc All rights reserved