Humoral rejection of human organ transplants

• Published in: Seminars in immunopathology 2003-09, Vol.25 (2), p.119-140
• Main Authors: MICHAELS, Paul J, FISHBEIN, Michael C, COLVIN, Robert B
• Format: Article
• Language: English
• Subjects: Antibody Formation; Biological and medical sciences; Complement C4 - analysis; Complement C4 - immunology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Graft Rejection - diagnosis; Graft Rejection - drug therapy; Graft Rejection - immunology; Graft Rejection - pathology; Histocompatibility Antigens Class I - immunology; Humans; Immunity, Cellular; Immunity, Innate; Immunosuppressive Agents - therapeutic use; Kidney Transplantation - immunology; Liver Transplantation - immunology; Lung Transplantation - immunology; Tissue, organ and graft immunology; Transplantation Immunology
• ISSN: 0344-4325; 1863-2297; 1432-2196; 1863-2300
• DOI: 10.1007/s00281-003-0139-x

Although T-cell mediated rejection has remained the most common form of acute rejection, humoral rejection now accounts for a substantial fraction in patients with kidney or heart allografts, and probably causes the majority of acute graft losses. The frequency, variously estimated at 20-30%, is attributed to improved methods of detection, including staining for C4d in tissues, which is more sensitive and specific than histological features. Detection of circulating anti-donor reactive antibody (usually to donor HLA antigens) confirms the diagnosis. The clinico-pathological entity of acute humoral rejection is well accepted in kidney and increasingly in heart transplantation. Recent evidence points to a new category of chronic humoral rejection, which accounts for about 60% of chronic rejection of kidneys. Importantly, the hallmark of humoral rejection, C4d, can be detected in the grafts before development of histological evidence of chronic rejection. Humoral rejection is generally not responsive to the usual anti-T cell immunosuppressive agents, but small, non-controlled trials suggest humoral rejection can be reversed with plasmapheresis, intravenous immunoglobulin, anti-CD20 and other treatments, all of which deserve formal clinical evaluation. Prophylaxis for chronic rejection is expected to require donor-specific serological monitoring and protocol biopsies.