title: Anticardiac myosin immunity and chronic allograft vasculopathy in heart transplant recipients.
abstract: Chronic allograft vasculopathy (CAV) contributes to heart transplant failure, yet its pathogenesis is incompletely understood. Although cellular and humoral alloimmunity are accepted pathogenic mediators, animal models suggest that T cells and Abs reactive to graft-expressed autoantigens, including cardiac myosin (CM), could participate. To test the relationship between CAV and anti-CM autoimmunity in humans, we performed a cross-sectional study of 72 heart transplant recipients: 40 with CAV and 32 without. Sera from 65% of patients with CAV contained anti-CM Abs, whereas <10% contained Abs to other autoantigens (p < 0.05), and only 18% contained anti-HLA Abs (p < 0.05 versus anti-CM). In contrast, 13% of sera from patients without CAV contained anti-CM Abs (p < 0.05; odds ratio [OR], associating CAV with anti-CM Ab = 13, 95% confidence interval [CI] 3.79-44.6). Multivariable analysis confirmed the association to be independent of time posttransplant and the presence of anti-HLA Abs (OR = 28, 95% CI 5.77-133.56). PBMCs from patients with CAV responded more frequently to, and to a broader array of, CM-derived peptides than those without CAV (p = 0.01). Detection of either CM-peptide-reactive T cells or anti-CM Abs was highly and independently indicative of CAV (OR = 45, 95% CI 4.04-500.69). Our data suggest detection of anti-CM immunity could be used as a biomarker for outcome in heart transplantation recipients and support the need for further studies to assess whether anti-CM immunity is a pathogenic mediator of CAV.
authors.affiliation: Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Safa
authors.initials: S
authors.lastname: Kalache
authors.forename: Rajani
authors.initials: R
authors.lastname: Dinavahi
authors.forename: Sean
authors.initials: S
authors.lastname: Pinney
authors.forename: Anita
authors.initials: A
authors.lastname: Mehrotra
authors.forename: Madeleine W
authors.initials: MW
authors.lastname: Cunningham
authors.forename: Peter S
authors.initials: PS
authors.lastname: Heeger
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D015415:Biomarkers / Q000097:blood; D024722:Cardiac Myosins / Q000276:immunology*; D002908:Chronic Disease; D015935:Complement C4b / Q000276:immunology; D003430:Cross-Sectional Studies; D004730:Endothelium, Vascular / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology*; D006680:HLA Antigens / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020556:Neutrophil Infiltration / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D010865:Pilot Projects; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D006680:HLA Antigens; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d; D024722:Cardiac Myosins