Lymphocyte autoantibodies and alloantibodies in HIV-positive haemophilia patients

Abstract

Immune parameters were studied in 86 haemophilia patients (six with AIDS) and 87 healthy controls. We found lymphocytotoxic alloantibodies in HIV-positive (HIV+) sera which reacted preferentially with B lymphocytes but also with T lymphocytes, and which reacted more frequently at 4 degrees C than at 37 degrees C. The antibodies were not directed against HIV-induced structures on T lymphocytes and they were reactive with both CD4+ and CD8+ lymphocytes. In addition to cytotoxic alloantibodies, cytotoxic autoantibodies were detected which coated patient lymphocytes in vivo. Increased proportions of in vivo-antibody-coated-cells were found in 37 of 86 haemophilia patients. Antibody binding was labile so that the immunoglobulins were partially removed from the lymphocyte surface by washing. The autoreactive antibodies were of IgG and IgM type, fixed complement as demonstrated by increased anti-C3d+ cells in the patients' blood, and reacted with CD4+ as well as CD8+ lymphocytes. There was a statistically significant correlation of increased Ig+ cells with HIV infection, decreased CD4/CD8 ratios, increased serum neopterin levels, and abnormal in-vitro responses to pooled allogeneic stimulator cells or CD3 monoclonal antibody. Patients with increased Ig+ cells were lymphopenic, had decreased absolute counts of CD4+, CD25+, CD21+ and OKM5+ cells, and higher percentages of CD8+ and OKIa1+ cells in their blood than patients with normal levels of Ig+ cells. Our data suggest a role of autoreactive anti-lymphocyte antibodies in the pathogenesis of acquired immunodeficiency.