The development of antibodies (Abs) to major histocompatibility (MHC) class I-related chain A (MICA) and human leukocyte antigen (HLA) and their role in the immunopathogenesis of chronic rejection (bronchiolitis obliterans syndrome [BOS]) after human lung transplantation (LTx) was analyzed. Sera from 80 LTx recipients were analyzed for anti-MICA and anti-HLA Abs using Luminex and flow PRA (panel reactive assay). Development of Abs either to MICA alone or MICA and HLA together significantly correlated (p < 0.01) with development of BOS. Kinetic analysis in the post-LTx period revealed that development of anti-HLA Abs (7.6 ± 4.7 months) preceded the development of anti-MICA Abs (10.0 ± 3.5 months). Abs to MICA alleles (*001 and *009) developed approximately 6 months after LTx and peak titers were present at the time of clinical diagnosis of BOS (16.3 ± 2.7 months). The development of Abs to both MICA and HLA was strongly associated with the development of BOS thereby suggesting a synergistic effect. Furthermore, immune response to mismatched HLA can lead to development of Abs to other MHC related antigens expressed on the airway epithelial cells. Cumulatively, these immune responses contribute to the pathogenesis of chronic rejection following human LTx.
Bibliographical noteFunding Information:
This publication was made possible by Grant Numbers HL056643 (T.M.) from the National Institutes of Health/National Heart Lung and Blood Institute ARRA Award and Training Grant T32-HL07776 (D.N.) from the National Institutes of Health (NIH) . Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The authors thank Miyuki Ozawa and Kevin Harrell (One Lambda Inc.) for providing positive control sera, and Billie Glasscock for assistance in submitting this manuscript.
Copyright 2010 Elsevier B.V., All rights reserved.
- Chronic rejection
- Lung transplantation