# TNFSF4/OX40L and IKZF1/IKAROS Genetic Variant Associations with Egyptian Juvenile Systemic Lupus Erythematosus (JSLE)

## TL;DR

This study finds that genetic variations in TNFSF4 and IKZF1 genes are linked to juvenile lupus in Egyptian children, affecting disease susceptibility and kidney outcomes.

## Contribution

This is the first study to investigate TNFSF4 and IKZF1 genetic variants in Egyptian children with juvenile systemic lupus erythematosus.

## Key findings

- TNFSF4 rs1234315 T allele and genotypes are significantly associated with increased JSLE susceptibility.
- IKZF1 rs11980379 T allele and genotypes correlate with reduced JSLE incidence and milder kidney disease.
- The TC + CC genotype of IKZF1 rs11980379 is linked to lower lupus nephritis occurrence.

## Abstract

Genetic variables, immune complex deposition, complement activation, hormonal factors, and immune cell dysregulation all contribute to varying degrees to the pathogenesis of Juvenile systemic lupus erythematosus (JSLE). Important immunological molecules that regulate different immune cells and are associated with autoimmune disorders are TNFSF4 and IKZF1. Single-nucleotide polymorphisms (SNPs), the most prevalent type of genetic variation in the human genome, may influence gene function if present. In this study, we assessed the possible effects of rs11980379 C/T in the IKZF1 gene and rs1234315 C/T in the TNFSF4 gene on the susceptibility of Egyptian children to SLE. In addition, we also studied the distribution of these genetic variants and SLE clinical outcomes. This is the first study that we are aware of that assesses the relationship between these loci and the illness in our population. To examine these genetic polymorphisms, we performed a real-time polymerase chain reaction using the TaqManTM SNP genotyping assay on the Artus Rotor-Gene Qiagen equipment (QIAGEN, Hilden, Germany). The allelic and genotypic frequencies of rs1234315 and rs11980379 were shown to be substantially linked with the disease.

Background: The etiopathogenesis of juvenile systemic lupus erythematosus (JSLE), a complex and complicated illness, is unknown. Genetic, environmental, and dysregulated immune system responses are all thought to contribute to the disease’s etiology. Important immunological molecules that regulate different immune cells and are associated with autoimmune disorders are TNFSF4 and IKZF1. Thus, our purpose was to discover if TNFSF4 and IKZF1 mutations left the Egyptian population genetically predisposed to SLE. Methods: Using real-time polymerase chain reaction (RT-PCR), polymorphism analysis of the TNFSF4 rs1234315 C/T and IKZF1 rs11980379 C/T genes was performed on extracted DNA from JSLE patients and healthy controls. Results: TNFSF4 frequencies (rs1234315 T allele, CT, TT genotypes, dominant and recessive models) were substantially associated with a higher incidence of JSLE (p < 0.05) compared to healthy controls. Conversely, IKZF1 frequencies (rs11980379 T allele, TC, TT genotypes, and dominant model) significantly correlated with a lower incidence of JSLE. Furthermore, the TC + CC rs11980379 genotype was identified as significantly associated with lower kidney biopsy grades and a lower incidence of lupus nephritis. Conclusions: Our findings suggest that TNFSF4 and IKZF1 polymorphisms affect vulnerability to juvenile SLE.