Cryptococcus neoformans is one of the most common causes of fungal disease in HIV-infected persons, but not all of those who are infected develop cryptococcal disease (CD). Although CD4+ T cell deficiency is a risk factor for HIV-associated CD, polymorphisms of phagocytic Fc gamma receptors (FCGRs) have been linked to CD risk in HIV-uninfected persons. To investigate associations between FCGR2A 131 H/R and FCGR3A 158 F/V polymorphisms and CD risk in HIV-infected persons, we performed PCR-based genotyping on banked samples from 164 men enrolled in the Multicenter AIDS Cohort Study (MACS): 55 who were HIV infected and developed CD and a matched control group of 54 who were HIV infected and 55 who were HIV uninfected. Using additive and allelic statistical models for analysis, the high-affinity FCGR3A 158V allele was significantly associated with CD status after adjusting for race/ethnicity (odds ratio [OR], 2.1; P = 0.005), as was the FCGR3A 158 VV homozygous genotype after adjusting for race/ethnicity, rate of CD4+ T cell decline, and nadir CD4+ T cell count (OR, 21; P = 0.005). No associations between CD and FCGR2A 131 H/R polymorphism were identified. In binding studies, human IgG (hIgG)-C. neoformans complexes exhibited more binding to CHO-K1 cells expressing FCGR3A 158V than to those expressing FCGR3A 158F, and in cytotoxicity assays, natural killer (NK) cells expressing FCGR3A 158V induced more C. neoformans-infected monocyte cytotoxicity than those expressing FCGR3A 158F. Together, these results show an association between the FCGR3A 158V allele and risk for HIV-associated CD and suggest that this polymorphism could promote C. neoformans pathogenesis via increased binding of C. neoformans immune complexes, resulting in increased phagocyte cargo and/or immune activation.

No abstract

Chronic inflammation contributes to a number of chronic diseases and can be assessed with C-reactive protein (CRP). In this longitudinal retrospective chart review, we investigate whether patients intensively counseled to eat a specific diet high in dark green leafy vegetables, and thus high beta-carotene, have reductions in plasma high-sensitivity CRP (hsCRP). We term this the Low Inflammatory Foods Everyday (LIFE) diet. Forty-three patients in a community practice instructed to eat the LIFE diet met inclusion criteria. The CRP levels were measured at least twice over the course of up to a year. Adherence to the diet was objectively assessed by measurement of plasma beta-carotene, which is abundant in dark green leafy vegetables, and subjectively by serial interviews. The change in beta-carotene was inversely correlated with change in CRP ( r = −0.68, P < .0001). Additionally, patients subjectively classified as adherent had higher beta-carotene ( P < .0001) and lower CRP ( P = .002) as compared with patients who were classified as nonadherent. These longitudinal findings suggest that adherence to the LIFE diet leads to increased beta-carotene and decreased CRP. Thus, this type of diet may reduce risk or severity of chronic diseases involving inflammation.