The aim of this study is to investigate the association between ICOS gene polymorphism and susceptibility to systemic lupus erythematosus (SLE), as well as its impact on disease severity.

Systemic lupus erythematosus (SLE) is a chronic, multiorgan, systemic autoimmune disease that affects almost all tissue and organ systems, has a varied clinical appearance, and fluctuates in severity among people and over time. The global incidence of SLE has been estimated at 5.14 per 100,000 person-years with mortality rates ranging from 6.7 to 37.8 %, with women five times more likely to be affected than men. The pathogenesis of SLE is complex and involves cells of both innate and adaptive immunity. The distinguishing feature of SLE is the production of autoantibodies, with the formation of immune complexes , and result in the inflammatory response of the immune system.Costimulatory signals, which include ligands and receptors and their interactions involving multiple types of signal information, are essential for the initiation, maintenance, and regulation of immune reactions. When costimulatory factors malfunction, complex abnormal immune responses with biological effects and ultimately clinical autoimmune diseases result. Inducible co-stimulator (ICOS) is the third member of the CD28/cytotoxic T-lymphocyte associated antigen-4 family and is involved in the proliferation and activation of T cells. The inducible T cell co-stimulator (ICOS) is expressed on T cells following peptide:MHC engagement with CD28 co-stimulation. The interaction of ICOS with its sole ligand the Inducible T-cell co-stimulatory ligand (ICOSL; also known as B7-related protein-1 or ICOSL) triggers key activities of T cells including cytokine production and differentiation into the T follicular helper (Tfh) cell lineage over effector lineages. Inducible T-cell co-stimulator (ICOS)-deficient people are unable to produce T follicular helper (Tfh) cells, which are CD4 T cells that migrate into B cell follicles and promote germinal centre (GC) reactions, according to research on human patients and mice models.

In this study, we aim to explore the possible association between potentially functional SNP rs11889031 of the ICOS gene and SLE in the Egyptian population.

Inclusion Criteria:

• Patients diagnosed with SLE based on 2019 EULAR/ACR Male or female. willing to provide written informed consent for participation and genetic testing

Exclusion Criteria:

• Other autoimmune diseases or chronic inflammatory disorders. Malignancy. Pregnancy or breastfeeding. Inability to provide informed consent.

group A: systemic lupus erythrematosus patients about 20 patients diagnosed with SLE based on 2019 EULAR/ACR.

group B:healthy controls 10 with no personal or family history of autoimmune diseases or chronic inflammatory disorders