Details

Autor(en) / Beteiligte

• Kalache, Safa
• Dinavahi, Rajani
• Pinney, Sean
• Mehrotra, Anita
• Cunningham, Madeleine W
• Heeger, Peter S.

Titel

Anti-cardiac myosin immunity and chronic allograft vasculopathy in heart transplant recipients1

Ist Teil von

• The Journal of immunology (1950), 2011-06, Vol.187 (2), p.1023-1030

Erscheinungsjahr

2011

Link zum Volltext

Quelle

Electronic Journals Library - Freely accessible e-journals

Beschreibungen/Notizen

• Chronic allograft vasculopathy (CAV) contributes to heart transplant failure, yet its pathogenesis is incompletely understood. While cellular and humoral alloimmunity are accepted pathogenic mediators, animal models suggest that T cells and antibodies 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 antibodies, while <10% contained antibodies to other autoantigens (p<0.05), and only 18% contained anti-HLA antibodies (p<0.05 vs. anti-CM). In contrast, 13% of sera from patients without CAV contained anti-CM antibodies (p<0.05, odds ratio, OR, associating CAV with anti-CM antibody=13, 95% CI: 3.79–44.6). Multivariate analysis confirmed the association to be independent of time posttransplant and the presence of anti-HLA antibodies (OR=28, 95% CI: 5.77–133.56). PBMC 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 antibodies 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 is a pathogenic mediator of CAV.