Abstract

BACKGROUND: The relevance of B-cell dysfunction for progression to AIDS among human immunodeficiency virus (HIV)-infected individuals has not been clearly defined. We evaluated the association between circulating κ and λ free light chains (FLCs), which are markers of B-cell dysfunction, and risk of developing an AIDS-defining opportunistic infection in HIV-infected men. METHODS: The study included 252 case patients with clinical AIDS and 252 HIV-infected controls from the Multicenter Hemophilia Cohort Study I. Case patients were matched to controls on birth date, specimen type, blood sample collection date, and CD4 cell count. Levels of κ and λ FLCs were measured in serum or plasma collected 0-2.5 years before selection. Elevated FLC levels (κ or λ, above the upper limit of normal) were classified as polyclonal (normal κ-λ ratio) or monoclonal (abnormally skewed κ-λ ratio). We used conditional logistic regression to estimate odds ratios (ORs) for AIDS. RESULTS: FLC levels were higher in case patients than in controls, for κ (median, 4.03 vs 2.98 mg/dL) and λ (3.77 vs 2.42 mg/dL) FLCs. Compared with normal levels, above-normal FLC levels were associated with AIDS (OR, 3.13 [95% confidence interval (CI), 1.78-5.49] for κ and 3.47 [2.31-5.20] for λ FLCs), and the association with AIDS was strengthened with increasing κ and λ FLC levels (P trends < .0001). Polyclonal FLC elevation was associated with a 4-fold increase in the risk of AIDS (OR, 3.85; 95% CI, 1.97-7.54), but monoclonal FLC elevation was not associated with AIDS. CONCLUSIONS: Circulating FLCs are associated with elevated risk of AIDS in HIV-infected individuals. Polyclonal B-cell dysfunction may contribute to HIV-related immune suppression and predispose to clinical AIDS events.