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. 2012 Nov 15;55(10):e103-8.
doi: 10.1093/cid/cis692. Epub 2012 Aug 14.

Free light chains and the risk of AIDS-defining opportunistic infections in HIV-infected individuals

Meredith S Shiels  1 , Ola Landgren, Rene Costello, Adriana Zingone, James J Goedert, Eric A Engels
Affiliations

Free light chains and the risk of AIDS-defining opportunistic infections in HIV-infected individuals

Meredith S Shiels et al. Clin Infect Dis. .

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.

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Figures

Figure 1.
Figure 1.
Associations of circulating free light chains (FLCs) with risk of AIDS among men with human immunodeficiency virus (HIV) infection. This figure presents the association between the risk of AIDS in HIV-infected men and levels of κ (A) or λ (B) FLCs. FLC results are expressed relative to the upper limit of normal (1.94 mg/dL for κ and 2.63 mg/dL for λ FLCs). Points represent odds ratios; vertical lines, 95% confidence intervals. Abbreviations: FLC, free light chain; ULN, upper limit of normal.
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References

    1. Lane HC, Masur H, Edgar LC, Whalen G, Rook AH, Fauci AS. Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1983;309:453–8. - PubMed
    1. Moir S, Fauci AS. B cells in HIV infection and disease. Nat Rev Immunol. 2009;9:235–45. - PMC - PubMed
    1. Pizzolo G, Vinante F, Morosato L, et al. High serum level of the soluble form of CD30 molecule in the early phase of HIV-1 infection as an independent predictor of progression to AIDS. AIDS. 1994;8:741–5. - PubMed
    1. Rizzardi GP, Tambussi G, Barcellini W, et al. Soluble CD30, tumour necrosis factor (TNF)-alpha, and TNF receptors in primary HIV-1 infection: relationship with HIV-1, RNA, clinical outcome and early antiviral therapy. J Biol Regul Homeost Agents. 1997;11:43–9. - PubMed
    1. Breen EC, Fatahi S, Epeldegui M, Boscardin WJ, Detels R, Martinez-Maza O. Elevated serum soluble CD30 precedes the development of AIDS-associated non-Hodgkin's B cell lymphoma. Tumour Biol. 2006;27:187–94. - PubMed

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