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||Free light chains and the risk of AIDS-defining opportunistic infections in HIV-infected individuals.
||Shiels MS, Landgren O, Costello R, Zingone A, Goedert JJ, Engels EA
||Clin Infect Dis
||2012 Nov 15
||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 Îº and Î» 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 Îº and Î» FLCs were measured in serum or plasma collected 0-2.5 years before selection. Elevated FLC levels (Îº or Î», above the upper limit of normal) were classified as polyclonal (normal Îº-Î» ratio) or monoclonal (abnormally skewed Îº-Î» 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 Îº (median, 4.03 vs 2.98 mg/dL) and Î» (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 Îº and 3.47 [2.31-5.20] for Î» FLCs), and the association with AIDS was strengthened with increasing Îº and Î» 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.