Serological and molecular survey for HTLV-I infection in a high-risk Middle Eastern group

To define the extent of human T-cell leukaemia virus (HTLV-I) infection among a group of Jewish immigrants to Israel with an increased frequency of adult T-cell leukaemia, various serological and molecular screening methods, including enzyme-linked immunosorbent assay (ELISA) for anti-HTLV-I, ELISA for antibody to recombinant HTLV-I p40 tax protein, and molecular detection of infection by polymerase chain reaction (PCR) amplification of HTLV-I proviral DNA from peripheral blood mononuclear cell DNA, were used. By HTLV-I ELISA the overall rate of infection was 12% (24 of 208) among immigrants from Khurusan, northeastern Iran; no HTLV-I carriers were detected among 111 unselected Jewish immigrants from other parts of Iran. There was unexplained clustering of HTLV-I infection within a cohort of 32 elderly women of similar geographic origin in a home for old people—14 were seropositive by ELISA and 19 of 29 were positive by PCR. The findings in this newly identified high-risk population suggest that in addition to ELISA, other screening techniques may be required to detect all carriers in high-risk populations

Selective capacity of metreleptin administration to reconstitute CD4+ T-cell number in females with acquired hypoleptinemia.

Leptin is an adipocyte-derived hormone that controls food intake and reproductive and immune functions in rodents. In uncontrolled human studies, low leptin levels are associated with impaired immune responses and reduced T-cell counts; however, the effects of leptin replacement on the adaptive immune system have not yet been reported in the context of randomized, controlled studies and/or in conditions of chronic acquired leptin deficiency. To address these questions, we performed a randomized, double-blinded, placebo-controlled trial of recombinant methionyl-human leptin (metreleptin) administration in replacement doses in women experiencing the female triad (hypothalamic amenorrhea) with acquired chronic hypoleptinemia induced by negative energy balance. Metreleptin restored both CD4(+) T-cell counts and their in vitro proliferative responses in these women. These changes were accompanied by a transcriptional signature in which genes relevant to cell survival and hormonal response were up-regulated, and apoptosis genes were down-regulated in circulating immune cells. We also observed that signaling pathways involved in cell growth/survival/proliferation, such as the STAT3, AMPK, mTOR, ERK1/2, and Akt pathways, were activated directly by acute in vivo metreleptin administration in peripheral blood mononuclear cells and CD4(+) T-cells both from subjects with chronic hypoleptinemia and from normoleptinemic, lean female subjects. Our data show that metreleptin administration, in doses that normalize circulating leptin levels, induces transcriptional changes, activates intracellular signaling pathways, and restores CD4(+) T-cell counts. Thus, metreleptin may prove to be a safe and effective therapy for selective CD4(+) T-cell immune reconstitution in hypoleptinemic states such as tuberculosis and HIV infection in which CD4(+) T cells are reduced