The incidence of childhood LCH in our study is higher than previously reported. In our patient cohort, LCH was more commonly diagnosed during the fall and winter season as compared to the spring and summer season. Whether this seasonal variation can be confirmed in larger studies and whether it has relevance for LCH pathophysiology remains to be elucidated.

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The biological phenotype of HIV-2 isolates can be divided into two groups, rapid/high and slow/low, based on the ability to infect CD4+ tumor cell lines. Similar differences in the biological phenotype of HIV-1 isolates are largely determined by the charge of two specific amino acids in the V3 loop of the envelope protein gp120. In this study we have sequenced the V3 loop and flanking regions of 14 HIV-2 isolates from Guinea-Bissau and the Ivory Coast and correlated the results to the biological phenotype of the isolates. The sequences were obtained by PCR amplification of DNA from peripheral blood mononuclear cells infected with the different isolates, followed by direct sequencing of the amplified products. Eleven other HIV-2 isolates with known V3 sequence and biological phenotype were also included. Thirteen of the 14 new isolates were classified as subtype A of HIV-2 and one as subtype B. The V3 loop of rapid/high HIV-2 isolates differed significantly from slow/low isolates in that it was more heterogeneous in sequence and had higher net charge. Mutations at two specific amino acid positions (313 and 314), often to positively charged amino acids, were also significantly associated with the rapid/high phenotype. There were no sequence differences between rapid/high and slow/low isolates in the regions that flank the V3 loop. Our findings indicate that there may be a high degree of similarity in the molecular features that underlie the biological phenotypes of HIV-1 and HIV-2 isolates.

Langerhans cell histiocytosis (LCH) is characterized by an accumulation of dendritic Langerhans cells in granulomatous lesions in the bone, skin, and other sites in the body. The pathogenesis of the disease remains unknown. We measured serum levels of the decoy receptor osteoprotegerin (OPG), an important regulator of bone metabolism as well as immune responses, in 18 children with single system (SS) or multi-system (MS) forms of LCH and 20 pediatric controls. OPG levels were significantly increased in LCH patients at diagnosis when compared with controls, and pretreatment levels of OPG were elevated in MS compared with SS patients. Moreover, OPG levels in LCH patients were elevated in patients with involvement of risk organs (liver, lungs, hematopoietic system, or spleen) when compared with patients without risk organ involvement, indicative of an association between OPG values and disease severity. We also observed a positive correlation between serum levels of OPG and tumor necrosis factor (TNF)-␣, a proinflammatory cytokine, at the time of onset of disease. These findings show, for the first time, that serum OPG levels are elevated in LCH patients, and suggest that OPG may play a role in the pathogenesis of this enigmatic disease. (Pediatr Res 59: 281-286, 2006)