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Background The prevalence of SLE and the spectrum of clinical manifestations vary widely in different races and geographical populations. Objective To investigate the possible role of ARID5B rs10821936 and rs10994982 polymorphism as a risk factor for the development of SLE in children (jSLE) and to evaluate their role in relation to clinical manifestations especially lupus nephritis (LN). Methods DNA extraction and Real-time PCR genotyping of ARID5B rs10821936 and rs10994982 were done for 104 jSLE and 282 healthy controls. Results The C allele and C containing genotypes (CC, CT and CC+CT) of ARID5B rs10821936 were higher in children with SLE (p = 0.009, OR = 1.56, 0.037, OR = 2.35, 0.016, OR = 1.81 and 0.008 OR = 1.88 respectively). ARID5B rs10994982 alleles, genotypes and haplotypes are not associated with jSLE (p > 0.05). The ARID5B rs10821936 and rs10994982 genotypes showed non-significant associations with LN, proliferative versus non proliferative and biopsy grades (p > 0.05). Conclusion ARID5B rs10821936 SNP may be a susceptibility risk factor for juvenile SLE in the studied cohort of Egyptian children.