A polymorphism in the IL1B gene (rs16944 T/C) is associated with cutaneous leishmaniasis caused by Leishmania guyanensis and plasma cytokine interleukin receptor antagonist. (November 2019) - da Silva, George Allan Villarouco
Highlights: Leishmania activate the NLRP3 inflammasome in infected macrophages and enhance the secretion IL-1β. Polymorphisms in IL1B and IL1RN genes are studied in 881 Cutaneous Leishmaniasis cases and 837 controls. Plasma Cytokines IL-1B is higher among patients while IL1Ra in controls. IL1B rs16944 is associated with susceptibility to CL caused L. guyanensis in the Amazonas. High producer of IL-1Ra seems to be resistant to Leishmania -infection. Abstract: Nod-like Receptor Protein3 (NLRP3) inflammasome in macrophages infected with Leishmania sp . enhances the secretion of IL-1β. Excess IL-1β production is linked to disease severity in patients with cutaneous leishmaniasis (CL) caused by L. mexicana . Blockade of the NLRP3 inflammasome in cell cultures from skin biopsies of patients with CL caused by L. braziliensis inhibited the release of IL-1β. We hypothesized that common single nucleotide polymorphisms in the IL1B and in its receptor antagonist IL1RN genes may be predictive of CL caused by L. guyanensis. The SNPs –511T/C (rs16944) and +3954C/T (rs1143634) of the IL1B and IL1RN VNTR (rs2234663) were assessed in 881 patients with CL and 837 healthy controls by PCR-RFLP and direct PCR respectively. Plasma cytokines levels were also assayed. The plasma levels of IL-1β were higher in patients compared to control subjects. In contrast, increased plasma levels of IL-1Ra were observed in controls. The rs16944 C/C genotype was more common among the patients (OR = 1.5 [95%CI 1.1–2.0]; P = 0.004) and the C allele suggests susceptibility to CL (OR = 1.2 [95%CI 1.1–1.4]; P = 0.003). The rs16944 C/C genotype shows a tendency to correlate with lower levels of the IL-1Ra cytokine. Low levels of IL-1Ra cytokine and rs16944 C/C genotype seem to confer susceptibility to L. guyanensis -infection in the Amazonas.