Evidence for translocation of microbial products in patients with idiopathic CD4 lymphocytopenia.

National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
The Journal of Infectious Diseases (Impact Factor: 5.78). 07/2009; 199(11):1664-70. DOI: 10.1086/598953
Source: PubMed

ABSTRACT Translocation of microbial products has been described in chronic human immunodeficiency virus (HIV) infection and correlates with activation of the immune system. We investigated the potential translocation of microbial products in idiopathic CD4 lymphocytopenia (ICL), a rare disorder characterized by low CD4 T cell counts in the absence of HIV infection. Plasma lipopolysaccharide (LPS) levels and T cell activation were measured in a cross-sectional cohort study of patients with ICL and HIV infection and healthy control subjects. Increases in CD4 T cell proliferation but not CD8 T cell proliferation were observed in patients with ICL. LPS levels were significantly elevated both in patients with ICL and in patients with HIV infection, and they were strongly correlated with the proportion of proliferating CD4 T cells in the cohort of patients with ICL (r = 0.88; P= .003). The proportions of T helper (Th) 17 and Th1 CD4 cells in peripheral blood were similar between patients with ICL, patients with HIV infection, and control subjects. These findings suggest a potential association of translocation of microbial products with perturbed CD4 T cell homeostasis in individuals with CD4 lymphopenic states other than HIV infection.

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    ABSTRACT: Idiopathic CD4 lymphocytopenia (ICL) is characterized by a low CD4+ lymphocyte count in the absence of HIV or other underlying etiologies. We report a case of a 57-year old man with ICL and giant cell arteritis (GCA) who developed pulmonary mucormycosis, which, to our knowledge, is the first report of these occurring in a patient with ICL. Abnormally low total lymphocyte or CD4+ cell counts occurring in patients with autoimmune disorders should alert clinicians to the possibility of ICL. Immunosuppressive treatment should be used with caution in this context.
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    ABSTRACT: Background. (1→3)-β-D-glucan (BDG) is a helpful diagnostic marker for many invasive fungal infections. However, BDG is not thought to be useful in diagnosing cryptococcosis. We evaluated the utility of BDG as an adjunct diagnostic tool for HIV-infected patients with suspected cryptococcal meningitis. Methods. BDG concentrations were measured in CSF (n=177) and serum (n=109) of HIV-infected Ugandans and South Africans with suspected meningitis using the Fungitell® assay. Correlations between BDG concentrations and quantitative CSF cryptococcal cultures, CSF cryptococcal antigen (CRAG) titers, and 18 different CSF cytokine concentrations were assessed using non-parametric tests. Mixed models evaluated longitudinal changes in CSF BDG concentrations. Survival analyses evaluated BDG's relationship with mortality. Results. The Fungitell® BDG assay provided 89% sensitivity and 85% specificity in CSF for cryptococcal meningitis. Serum sensitivity was suboptimal (79%). CSF BDG concentrations at diagnosis were median (IQR) 343 (200-597) pg/mL in cryptococcal patients and 37 (23-46) pg/mL in patients without cryptococcosis. Sensitivity in CSF improved to 98% (53/54) when initial fungal burdens were ≥10,000 colony forming units (CFU)/mL. BDG normalized rapidly after initiating antifungal therapy. Baseline BDG concentrations correlated with CSF fungal burden (rho=0.820, P<.001), CSF CRAG lateral flow assay titers (rho=0.780, P<.001) and MCP-1 levels in CSF (P=.047). In cryptococcal meningitis patients, BDG ≥500 pg/mL at diagnosis was associated with increased 10-week mortality. Conclusions. BDG is detectable in the CSF of HIV-infected patients with Cryptococcus, and may provide useful prognostic information. Sensitivity is less than CRAG; however, BDG normalizes rapidly, unlike CRAG, making BDG potentially useful in diagnosing recurrent episodes.
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    Life sciences and space research 04/2014; 1:10-43. DOI:10.1016/j.lssr.2014.02.004


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