Anti-neutrophil cytoplasmic autoantibodies in patients with symptomatic HIV infection.

Abstract

Antibodies against cytoplasmic antigens of neutrophils, producing perinuclear (p-ANCA) as well as cytoplasmic staining with central accentuation (c-ANCA), have been described in non-HIV-infected patients with specific pathology such as glomerulonephritis and vasculitis. Here, we report on a patient with a vasculitis-like syndrome and a positive ANCA-test who appeared to be infected by HIV. Further analysis revealed that ANCA, p-ANCA as well as c-ANCA without central accentuation can be demonstrated in the serum of HIV+ individuals. In a cross-sectional study on individuals in different stages of HIV infection, we found that the occurrence of ANCA was limited to the symptomatic stages of HIV infection: p-ANCA was found in one out of 10 ARC patients and in two out of 11 AIDS patients with malignancies (AIDS-MAL), but not in AIDS patients with opportunistic infections (AIDS-OI). c-ANCA was found in four of the ARC patients, in two of the 14 AIDS-OI patients and in two AIDS-MAL patients. The presence of ANCA was not related to the degree of hypergammaglobulinaemia nor to specific symptomatology. ANCA containing sera from HIV+ individuals did not react with HEp2 cells nor with cytoplasmic antigens of lymphocytes, natural killer (NK) cells or eosinophils. Five out of the 11 (two p-ANCA and three c-ANCA) sera reacted weakly with cytoplasmic antigens of monocytes. All sera reacted with karyoplasts but not with cytoplasts prepared from neutrophils. These results suggest that HIV-ANCA might be directed against myeloid cell-specific granule constituents. However, sandwich-ELISAs with MoAbs against granule antigens that are frequently the target antigens of ANCA in HIV- individuals were negative. Also immunoprecipitation and immunoblotting, using lysates of neutrophil granules, did not allow further identification of the target antigens of HIV-ANCA