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Cutaneous leishmaniasis (CL) affects the lives of 0.7-1 million people every year causing lesions that take months to heal. These lesions can result in disfiguring scars with psychological, social and economic consequences. Antimonials are the first line of therapy for CL, however the treatment is lengthy and linked to significant toxicities; further, its efficacy is variable and resistant parasites are emerging. Shorter or lower dose antimonial treatment regimens, which would decrease the risk of adverse events and improve patient compliance, have shown reduced efficacy and further increase the risk emergence of antimonial-resistant strains. The progression of lesions in CL is partly determined by the immune response it elicits, and previous studies showed that administration of immunomodulatory type D CpG ODNs, magnifies the immune response to Leishmania and reduces lesion severity in nonhuman primates (NHP) challenged with Leishmania major or Leishmania amazonensis. Here we explored whether the addition of a single dose of immunomodulating CpG ODN D35 augments the efficacy of a short-course, low-dose pentavalent antimonial treatment regimen. Results show that macaques treated with D35 plus 5mg/kg sodium stibogluconate (SbV) for 10 days had smaller lesions and reduced time to re-epithelization after infection with Leishmania major. No toxicities were evident during the studies, even at doses of D35 10 times higher than those used in treatment. Critically, pentavalent antimonial treatment did not modify the ability of D35 to induce type I IFNs. The findings support the efficacy of D35 as adjuvant therapy for shorter, low dose pentavalent antimonial treatment., Competing Interests: Daniela Verthelyi is named as an inventor on a patent covering D35 filed on April, 1999, US 7,960,356 B2 under the Serial number 60/128,898. WO2000/061151. The patent is owned by the US government and licensed to DNDi.

Gm and Km as well as HLA-A, HLA-B, and HLA-DR phenotype frequencies were examined in 64 well-defined IgA nephropathy patients. The patients were divided into subpopulations according to clinical symptoms, e.g. macrohematuria and chronic renal failure (CRF). In patients with CRF the frequency of the Gm1,3,17;5,13,21 phenotype tended to be increased (p = 0.016; pcorr = 0.08). The frequency of the HLA-DR phenotype with only one antigen (HLA-DR-) was increased in the whole population (p less than 0.001; pcorr less than 0.011), which appeared to be confined to the patients with macrohematuria (p less than 0.001; pcorr less than 0.01) and non-CRF (p less than 0.001; pcorr less than 0.011). Patients with the Gm1,3,17;5,13,21 phenotype developed a CRF significantly earlier (p = 0.009; pcorr = 0.045) than patients with other Gm phenotypes. These data suggest that clinically observed subpopulations of IgA nephropathy patients differ in immunogenetic background.

Since its definition is purely descriptive, IgA-nephropathy (IGAN) may comprise more disease entities which share the (epi)phenomenon of mesangial IgA-depositions. IGAN patients with macroscopical hematuria (macro-H) differ from the other IGAN patients in 9 aspects: history, HLA-DR, Gm-allotypes, actuarial kidney survival, initial creatinine clearance, initial proteinuria, initial microhematuria, age at presentation and light microscopy of the renal biopsy. The difference in the last five parameters may either be explained by the existence of subentities or by earlier detection of patients with macro-H. The dissimilarity in the first four parameters can only be due to the former theory. Therefore, we conclude that IGAN probably comprises at least two disease entities.