Cytokine and IRF5 Gene Polymorphisms Associated With Susceptibility and Organ Damage in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease resulting from the complex interplay between genetic, environmental, and immunological factors. Genetic polymorphisms in cytokine and transcription factor genes have been proposed as key contributors to disease susceptibility and clinical heterogeneity.

To evaluate the association between selected single nucleotide polymorphisms (SNPs) in TNF-α, IL-1, IL-8, and IRF5 genes and the risk of SLE, as well as their correlation with specific organ system involvement.

We conducted a case-control study including 156 SLE patients and 104 healthy controls from the Algerian population. Seven SNPs were genotyped using TaqMan assays: IL-1 (-31 C/T and -511 C/T), TNF-α (-308 G/A and -238 G/A), IL-8 (-251 A/T), and IRF5 (-13176 A/C and -3835 G/T). Genotype and allele frequencies were compared between groups and correlated with clinical phenotypes.

The immunogenetic study revealed a significant association between G allele of the -3835 G/T polymorphism of the IRF5 gene and the risk of genetic susceptibility to the lupus (p = 0.012). Stratification according to clinical manifestations has showed that the G allele of the -31 C/T polymorphism of the IL-1 gene is associated with joint damage (p = 0.024) and the A allele of -511 C/T polymorphism predisposes to hematological damage (p = 0.041) in lupus patients. Also, the A allele of the TNFα -238 G/A polymorphism was associated with neuropsychiatric impairment (p = 0.036) and the A allele of -251A/T SNP of the IL-8 gene to the joint damage (p = 0.04).

Our findings support a role for IRF5 and cytokine gene polymorphisms in the genetic predisposition to SLE and its clinical manifestations. These polymorphisms may serve as potential biomarkers for disease risk stratification and personalized patient management, particularly in underrepresented populations such as North Africans.