Anti-phospholipid antibodies and CD5+ B cells in HIV infection

Abstract

This cross-sectional study evaluates the correlation between anti-phospholipid antibodies and CD5+ B cells in 110 patients infected with HIV-1. There were 89.1% of the patients who had IgG antibodies against cardiolipin and phosphatidylserine. The prevalence of IgM and IgA antibodies was < 22%. AIDS was associated with lower frequencies of IgM antibodies against cardiolipin (P = 0.05) and IgG-antibodies against cardiolipin and phosphatidylserine (P = 0.011). Drug users had higher IgM antibodies against phospholipids than patients from other risk groups (P = 0.02). A history of thromboembolic events was not accompanied by higher levels of anti-phospholipid antibodies (P > 0.2). No correlation between anti-phospholipid antibodies and CD5+ B cells was detected. Percentage part of CD5+ B lymphocytes was elevated in all patients and absolute CD4+ T lymphocyte counts and HIV p24 antigen were inversely correlated. In advanced disease a significant reduction of anti-phospholipid antibodies was contrasted with persistent elevation of CD5+ B lymphocytes. These observations may reflect immunological dysfunction involving apoptosis and endothelial damage rather than polyclonal B cell hyperstimulation. A possible explanation would be that in HIV infection an increased rate of spontaneous apoptosis in peripheral blood lymphocytes is accompanied by functional and structural changes of mitochondria. Therefore, structurally altered mitochondrial phospholipids could serve as antigen to induce specific humoral immune responses.

Fig. 1

IgG anti-cardiolipin antibodies (ACLA) and IgG anti-phosphatidylserine antibodies (APSA) levels according to the clinical (a) and immunological (b) stage. Measurements of ACLA and APSA were performed as described in Subjects and Methods. The frequency of IgG ACLA and IgG APSA was significantly lower in patients with full-blown AIDS than in those of category A or B (both P = 0.011, Fisher's two-tailed exact test). Similar results were obtained comparing the different immunological groups. The hatched area indicates the negative range.

Fig. 2

Survival estimations comparing IgG anti-phosphatidylserine antibody (APSA)⁺ (○) and IgG APSA⁻ (•) individuals. Individuals with severe immunodeficiency (CD4⁺ T lymphocytes < 0.2/nl) and positive APSA IgG tended to have a longer survival compared with subjects with severe immunodeficiency, but negative APSA IgG (P = 0.106, log-rank test).

Fig. 3

Correlation of CD4⁺ T lymphocytes with the proportion of B1 lymphocytes in the peripheral blood. CD5⁺ B lymphocytes were inversely correlated with absolute CD4⁺ T lymphocyte counts (r² = − 0.18, P = 0.037) and immune-complex-dissociated HIV p24 antigen in serum (r² = − 0.19, P = 0.029).

Fig. 4

Survival in individuals with immunological stages 2 and 3 compared according to the proportions of CD5⁺ B lymphocytes. Individuals with a high proportion of CD5⁺ B lymphocytes and only moderate CD4⁺ T lymphocyte depletion (○) tended to have a longer survival than those with CD5⁺ B lymphocytes < 50% of all B lymphocytes (•) (P = 0.087, log-rank test).