Rapamycin differentially inhibits S6Ks and 4E-BP1 to mediate cell-type-specific repression of mRNA translation

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Abstract
OBJECTIVE: Autommune diseases could constitute one emerging cause of morbidity in patients infected with human immunodeficiency virus (HIV) due to the chronicity of the infection and to the high level of B cell stimulation induced by HIV. We conducted a cross-sectional study investigating the clinical and biological signs of autoimmunity in HIV infected patients. METHODS: We studied the following plasma immunological variables: antinuclear antibodies (ANA) and antibodies to extractable nuclear antigens, antiphospholipids, anticardiolipins (aCL), antineutrophil cytoplasmic antibodies (ANCA), rheumatoid factor (RF), cryoglobulinemia, total complement, and C4 factor. HIV-RNA, CD4+ cell count, and serological status for hepatitis B (HBV) and C virus (HCV) were also studied. Clinical signs of autoimmune diseases were noted. RESULTS: In total, 97 patients were investigated (men 74%). Median age was 38 years (range 20-64). Median CD4+ count and HIV-RNA were 333/mm3 and 1662 copies/ml, respectively. Coinfection by HBV and HCV was present in 7% and 64% of the patients. In patients with HIV only, we detected cryoglobulinemia in 17% of patients, a positive RF in 19%, ANA > 1/100 in 21%, aCL in 51%, and ANCA > 1/20 in 17% (most of them type C by ELISA). There was a trend for a higher level of cryoglobulinemia and aCL in patients having CD4 lymphocyte counts > 350/mm3 than in others (25% vs 11%, p = 0.26, and 63% vs 42%, p = 0.23, respectively). Patients coinfected with HCV had a higher prevalence of cryoglobulinemia than HCV-free patients (42% vs 17%; p = 0.01). Prevalence of other immunological abnormalities was not different between patients with HIV only and HCV coinfected patients. Thirty patients expressed at least one clinical sign compatible with autoimmune disease. Patients with cryoglobulinemia more often had coinfection with HCV (OR 6.64, 95% CI 1.87-23.57) and IgM > 1.9 g/l (OR 6.16, 95% CI 2.15-17.67). CONCLUSION: Humoral immunological abnormalities are frequent in patients with HIV, but are rarely associated with severe clinical signs.