Antibody‐Mediated Rejection in Human Cardiac Allografts: Evaluation of Immunoglobulins and Complement Activation Products C4d and C3d as Markers

• Published in: American journal of transplantation Vol. 5; no. 11; pp. 2778 - 2785
• Main Authors: Rodriguez, E. R., Skojec, Diane V., Tan, Carmela D., Zachary, Andrea A., Kasper, Edward K., Conte, John V., Baldwin, William M.
• Format: Journal Article
• Language: English
• Published: Oxford UK Munksgaard International Publishers 01.11.2005; Blackwell
• Subjects: Antibody‐mediated rejection; Biological and medical sciences; Biomarkers - blood; Biopsy; C3d; C4d; complement; Complement Activation; Complement C3d - immunology; Complement C4b - immunology; Follow-Up Studies; Graft Rejection - immunology; heart transplant; Heart Transplantation - immunology; Heart Transplantation - pathology; Humans; Immunoglobulin A - blood; Immunoglobulin G - blood; Immunoglobulin M - blood; Immunoglobulins - blood; macrophages; Medical sciences; Peptide Fragments - immunology; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Time Factors; Transplantation, Homologous - immunology; Heart; Human; Evaluation; Graft(material); Immunoglobulins; Antibody; Biological marker; Transplantation; Activation; Complement; Homotransplantation; Antibody-mediated rejection; Rejection; C4d; macrophages; Treatment; C3d; Surgery; Graft; heart transplant; Circulatory system; Macrophage
• ISSN: 1600-6135; 1600-6143
• DOI: 10.1111/j.1600-6143.2005.01074.x

Antibody‐mediated rejection (AMR) in human heart transplantation is an immunopathologic process in which injury to the graft is in part the result of activation of complement and it is poorly responsive to conventional therapy. We evaluated by immunofluorescence (IF), 665 consecutive endomyocardial biopsies from 165 patients for deposits of immunoglobulins and complement. Diffuse IF deposits in a linear capillary pattern greater than 2+ were considered significant. Clinical evidence of graft dysfunction was correlated with complement deposits. IF 2+ or higher was positive for IgG, 66%; IgM, 12%; IgA, 0.6%; C1q, 1.8%; C4d, 9% and C3d, 10%. In 3% of patients, concomitant C4d and C3d correlated with graft dysfunction or heart failure. In these 5 patients AMR occurred 56–163 months after transplantation, and they responded well to therapy for AMR but not to treatment with steroids. Systematic evaluation of endomyocardial biopsies is not improved by the use of antibodies for immunoglobulins or C1q. Concomitant use of C4d and C3d is very useful to diagnose AMR, when correlated with clinical parameters of graft function. AMR in heart transplant patients can occur many months or years after transplant.