AB1120 FCΓRIIB POLYMORPHISM IN SLE: ASSOCIATION WITH CLINICAL PHENOTYPES, DISEASE ACTIVITY AND LEVELS OF CYTOKINES (IL-6, IL-17 AND TNF-α)

Background: Systemic lupus erythematosus (SLE) is a prototype autoimmune disease of multifactorial origin. Pathogenesis of SLE involves genetic, environmental, hormonal and epigenetic factors that lead to production of autoantibodies and immune complex formation. This in turn elicits inflammation by engaging Fc receptors (FcRs), activation of complements and release of various cytokines. FcγRs (Fc-Gamma receptors) belong to the immunoglobulin superfamily of receptors. They are divided into three families (FcγRI (CD64), FcγR II (CD32) and FcγR III (CD16)). All are activating receptors while FcγRIIB is the only inhibitory receptor. Loss of function SNPs in FcγRIIB is expected to cause increased activation of B-cells leading to production of auto-antibodies. The T-to-C transition in exon 5 (rs1050501) of FcγRIIB, is a loss of function SNP that has been reported to be associated with SLE worldwide. Considering the important role of FcγRIIB in dampening immune response, this current study was designed to determine the prevalence of this polymorphism in a cohort from Eastern India. Objectives: To determine the prevalence of FcγRIIB polymorphism in patients with SLE and its association with clinical phenotypes, disease activity and serum levels of IL-6, IL-17 and TNF-⍺. Methods: This is a cross sectional, observational, single center study. 190 adult patients fulfilling the SLICC criteria for SLE were enrolled along with 155 healthy controls after taking informed consent(IEC-1298/2023). Baseline clinical and demographic features were recorded into a predesigned proforma. Disease activity was scored using SLEDAI-2K.Patients with active infections and pregnancy were excluded. FcγRIIB polymorphism was assessed using PCR for both cases and controls. Serum levels of cytokines IL-6, IL-17 and TNF-⍺ were analyzed by ELISA as per the manufacturers protocol. Fisher exact test was used to explore the distribution of FcγRIIB polymorphism (I263T) among SLE patients and healthy controls, and in addition the association of the genetic variants with clinical manifestation was also investigated. Furthermore, possible association of FcγRIIB genetic variants with the levels of cytokines was performed by one way Analysis of Variance. Results: Out of 190 patients, 181(95.26%) were females and 9(4.71%) were male. The mean age of the subjects was 26.2±8.45 years. Mean disease duration in our cohort was 38.94±36 months.153(80.5%) had mucocutaneous manifestations, 124(65.26%) had renal involvement and 45(23.68%) had NPSLE manifestations. Most patients had active disease with mean SLEDAI of 11.5±7.91. Prevalence of FcγRIIB polymorphism (rs1050501) homozygous type T/T was higher in SLE patients compared to healthy controls 29/190 (15.2%) Vs 5/155(3.22%), p=0.001. T allele was present in higher numbers in SLE patients compared to healthy controls 136/380 (35.78%) Vs 78/310(25.16%), p=0.002. There was no significant difference between the levels of cytokines among various genotypes TNF-⍺ (I/I: 35.88±115.4 pg/ml, I/T: 15.0±39.47 pg/ml, T/T:47.89±62.69 pg/ml), IL-17A (I/I:36.62±87.38 pg/ml, I/T:33.45±76.11 pg/ml, T/T:77.31±103.8 pg/ml). Although most patients had active disease, there was no significant difference between distribution of SLEDAI among the three genotypes and there was no correlation between SLEDAI and serum cytokine levels. Conclusion: FcγRIIB homozygous type T/T polymorphism (rs1050501) is more prevalent among Indian SLE patients. REFERENCES: NIL. Acknowledgements: NIL. Indian Rheumatological Association. Disclosure of Interests: None declared.