IL-23R Variant rs11805303 Is Associated With Susceptibility to the Development of Cutaneous Leishmaniasis in Leishmania guyanensis–Infected Individuals

• Published in: The Journal of infectious diseases Vol. 225; no. 1; pp. 163 - 171
• Main Authors: Santos da Silva, Lener, Santo Júnior, José do Espírito, de Mesquita, Tirza Gabrielle Ramos, Santos, Veronica Alice Marinho, de Souza, Josué Lacerda, de Araújo, Felipe Jules, da Silveira Júnior, Cláudio Marcello, da Silva, Cilana Chagas, Queiroz, Krys Layane Guimarães Duarte, Sequera, Héctor David Graterol, Guerra, Marcus Vinitius de Farias, de Souza, Mara Lúcia Gomes, Ramasawmy, Rajendranath
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 05-01-2022
• Subjects: Alleles; Case-Control Studies; Cutaneous leishmaniasis; Gene polymorphism; Humans; IL-1β; Interleukin 17; Interleukin 23; Interleukin 6; Interleukin-17 - blood; Interleukin-23 - blood; Interleukin-23 - genetics; Leishmania guyanensis; Leishmania guyanensis - genetics; Leishmania guyanensis - isolation & purification; Leishmaniasis, Cutaneous - diagnosis; Leishmaniasis, Cutaneous - genetics; Parasitic diseases; Pathogenesis; Plasma levels; Polymerase chain reaction; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Receptors, Interleukin; Restriction fragment length polymorphism; Risk factors; γ-Interferon; variant; cutaneous leishmaniasis; susceptibility; Leishmania guyanensis; IL23R variant
• DOI: 10.1093/infdis/jiab320
• EISSN: 1537-6613
• ISSN: 0022-1899

Abstract
Background
Emerging evidence suggests that the interleukin (IL) 17/ IL-23 axis may play a role in the pathogenesis of leishmaniasis. Our aim was to investigate whether the IL-23R variant rs11805303 is a risk factor for the development of cutaneous leishmaniasis (CL) in Leishmania guyanensis–infected individuals.
Methods
We genotyped by polymerase chain reaction–restriction fragment length polymorphism the rs11805303 C/T in 828 patients with CL and 806 healthy individuals. Plasma tumor necrosis factor–α, IL-6, interferon-γ, IL-1β, and IL-17 were measured with the Bioplex assay.
Results
The distribution of the genotypes differed between patients with CL and healthy controls with a common odds ratio of 1.78 (P = 2.2 × 10–11) for the disease-associated T allele. Leishmania guyanensis–infected individuals homozygous for the T allele show a 200% increased risk of progressing to disease development, with a 95% confidence interval ranging from 81% to 400% (P = 9.9 × 10–6) in comparison to individuals homozygous for the C allele. Males homozygous for the T allele have higher plasma levels of IL-17 compared with heterozygous or homozygous CC individuals.
Conclusions
The present association of the IL-23R variant rs11805303 with the development of CL suggests that the IL-17/IL-23 axis may play an important role in the pathogenesis of CL.
The IL23R variant is associated with susceptibility to cutaneous leishmaniasis (CL) caused by Leishmania guyanensis and influences plasma circulating levels of IL-17. The IL-17/IL-23 axis may play a role in the pathogenesis of CL in genetically susceptible L. guyanensis–infected individuals.