Clinical implications of autoantibodies in HIV infection

Objective: To study the frequency and specificity of autoantibodies in HIV-infected subjects and their association with rheumatic manifestations, immunodeficiency, and prognosis. Design: Prospective study of sequentially selected HIV-infected patients. Indirect immunofluorescence reading was performed by two independent observers blinded for the patient diagnosis. Enzyme-linked immunosorbent assay (ELISA) was performed using coded serum samples. Setting: The study was performed at the Infectious Disease and Rheumatology Divisions of a tertiary care university hospital. Patients: One hundred sequentially selected HIV-infected patients formed group A. Controls included 80 non-HIV-infected high-risk individuals (group B), 20 herpesvirus-infected patients (group C), and 30 healthy blood donors (group D). Main outcome measures: Patients were followed for 2 years and evaluated for the presence of immunodeficiency, rheumatic manifestations, circulating autoantibodies and total CD4+ cell count. Indirect immunofluorescence was used to investigate antinuclear antibodies, antibodies to native DNA, smooth muscle, parietal cell, glomeruli, thyroid, and neutrophil cytoplasm. Agglutination was used to detect antibodies to erythrocytes and rheumatoid factor. ELISA was used to determine antibodies to cardiolipin and denatured DNA. CD4+ lymphocytes were counted by flow cytometry. Immunoglobulin (Ig) G, IgM and IgA serum levels were determined by radial immunodiffusion. Results: HIV-infected patients presented higher overall frequency of autoantibodies than the other groups. No difference was observed between immunodeficient and asymptomatic HIV-infected patients. The most frequent specificities were antibodies to cardiolipin and to denatured DNA. Ig serum levels did not correlate with the occurrence of autoantibodies. The presence of autoantibodies was associated with lower CD4+ cell counts and with higher mortality within 2 years. Rheumatic manifestations were observed in 35 HIV-infected patients and were not associated with the occurrence of autoantibodies or the presence of immunodeficiency. Conclusions: HIV infection is associated with an increased incidence of autoantibodies. Although not related to the occurrence of rheumatic manifestations, the presence of autoantibodies was significantly associated with lower CD4+ lymphocyte counts and increased mortality, which implies prognostic significance to this phenomenon in the context of HIV infection.