Interleukin 10 Gene Polymorphisms and Development of Post Kala-Azar Dermal Leishmaniasis in a Selected Sudanese Population

Abstract

Background: Post kala-azar dermal leishmaniasis (PKDL) is a cutaneous form of disease that develops at variable times after individuals have received treatment for clinical visceral leishmaniasis (VL). The study aimed to investigate the possible role of interleukin 10 (IL-10) and development of PKDL. Methods: 77 families composed of 41 complete case-parent trios and 36 case-parent pairs from the Masalit ethnic group were genotyped for 3 IL10 promoter polymorphisms: -1082A/G, -819C/T and -592C/A. Results: Single point analysis using the transmission disequilibrium test showed no evidence of association between any of these IL10 promoter single nucleotide polymorphisms (SNPs) and development of PKDL. Haplotype analysis performed using TRANSMIT showed borderline significance between PKDL and the haplotype AA across -592C/A and -1082A/G (p = 0.053). Haplotypes GCC (0.33) and ATA (0.30) were the common haplotypes in this Sudanese population. Allele frequencies for the 3 SNPs differed significantly in Sudan compared to other African (Gambian, Malawian, YRI) populations. Conclusion:In Sudan post kala-azar dermal leishmaniasis (PKDL) is a known complication of visceral leishmaniasis (VL) caused by Leishmania donovani and occurs in some patients after treatment and cure of VL. PKDL occurs with a frequency of 56–62%, usually after a latent phase from months to years [1, 2] . Clinical characterization of the disease was previously described [3] . Experimental studies indicate that interleukin 10 (IL-10) plays an important regulatory role in the progression of VL. IL-10 was the most prominent cytokine in PKDL lesions [4] with high levels also observed in plasma [5] . However, interferon- (IFN- ) was also seen in all lesions [4] and was detected in keratinocytes and/or sweat glands of patients who developed PKDL. In response to leishmanial antigens, peripheral blood mononuclear cells from most Sudanese PKDL patients proliferate and produce IFN- and IL-10 [4, 5] . Silva et al. (1992) postulated that the presence of IL- 10 in the skin lesions could block the action of IFN