Clinical Significance of Ikaros in Systemic Lupus Erythematosus (SLE): A Systematic Literature Review

Systemic lupus erythematosus (SLE) is a multi-systemic chronic autoimmune disease. Ikaros is a family member of transcription factors, encoded by the Ikaros family zinc finger 1 (IKZF1) gene. It is important in hematopoiesis and immune system regulation as it helps in lymphoid cell differentiation. Ikaros functions in the pathogenesis and therapeutic target in SLE are well demonstrated in mice. This systematic review highlighted the clinical significance of Ikaros and IKZF1 in SLE patients via a comprehensive search using OVID, PubMed, and Cochrane databases. The following terms "SLE", "lupus", "Ikaros transcription factor", "Ikaros zinc finger" and "IKZF" were searched and all of the relevant publications were scrutinised. Only human studies were included. A total of 22 relevant publications of Ikaros in SLE patients were included. IKZF1 polymorphisms were demonstrated to be significantly associated with SLE across different ethnicities of SLE. This association had led to clinical trials in SLE, using iberdomide that targets Ikaros. However, studies on the Ikaros gene expression and protein levels were found to be conflicting in SLE, which suggested clinical heterogeneity of the disease. In conclusion, further studies are needed to determine the exact effects of Ikaros and which subtypes of SLE patients will benefit from treatment.