DOI: 10.4103/bbrj.bbrj_41_26 ISSN: 2588-9834

Molecular and Immunological Characterization of Interleukin-40 and Interleukin-41 in Graves’ Disease Patients: An Iraqi Cohort Study

Adhraa Saad Jaber, Reema Mohammed Abed
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Background:

Graves’ disease (GD) is an autoimmune thyroid disorder in which the roles of interleukin-40 (IL-40) and IL-41 remain poorly understood. We characterized the serological, transcriptional, and genetic profiles of these cytokines in an Iraqi GD cohort.

Methods:

In this exploratory case–control study, 50 GD patients and 50 healthy controls were recruited. Serum IL-40 and IL-41 were quantified by enzyme-linked immunosorbent assay (ELISA), peripheral-blood mRNA expression by quantitative real-time polymerase chain reaction, and three IL40 single-nucleotide polymorphisms (SNPs; rs2310998, rs2004339, rs2310999) plus one IL41 SNP (rs2038043973) by Sanger sequencing. P values were Bonferroni-corrected, and multivariable logistic regression was adjusted for age, body mass index, and treatment duration.

Results:

Serum IL-40 was significantly lower ( P < 0.0001) and IL-41 significantly higher ( P = 0.010) in GD than in HC. IL40 mRNA was upregulated 2.5-fold ( P = 0.005) and IL41 mRNA downregulated 0.65-fold ( P < 0.0001). After Bonferroni correction and adjustment for confounders, the rs2310998-GA genotype, rs2310999-TG/GG genotypes and G allele, and the AAG, GAG, and AGT haplotypes were significantly associated with GD susceptibility. The rs2004339 individual-genotype effects and the GAT haplotype were nominally significant but did not survive correction.

Conclusion:

IL-40 and IL-41 show opposing serological and transcriptional associations with GD, and several IL40 polymorphisms are associated with disease susceptibility in this Iraqi cohort. Functional validation in larger, multiethnic cohorts is required before clinical translation.

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