title: Development of antibodies to human leukocyte antigen precedes development of antibodies to major histocompatibility class I-related chain A and are significantly associated with development of chronic rejection after human lung transplantation.
abstract: 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.
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Nataraju
authors.initials: N
authors.lastname: Angaswamy
authors.forename: Deepti
authors.initials: D
authors.lastname: Saini
authors.forename: Sabarinathan
authors.initials: S
authors.lastname: Ramachandran
authors.forename: Dilip S
authors.initials: DS
authors.lastname: Nath
authors.forename: Donna
authors.initials: D
authors.lastname: Phelan
authors.forename: Ramsey
authors.initials: R
authors.lastname: Hachem
authors.forename: Elbert
authors.initials: E
authors.lastname: Trulock
authors.forename: G Alexander
authors.initials: GA
authors.lastname: Patterson
authors.forename: T
authors.initials: T
authors.lastname: Mohanakumar
mesh_terms: D000328:Adult; D000917:Antibody Formation; D001324:Autoantigens / Q000276:immunology*; D001989:Bronchiolitis Obliterans; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D006680:HLA Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism*
chemical_list: D001324:Autoantigens; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; C099187:MHC class I-related chain A