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Abstract Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies and the deposition of immune complexes, affecting a wide range of organs. Genetic factors, environmental factors and hormonal factors are believed to contribute to the occurrence of SLE. However, the pathogenesis of SLE is complex and remains unknown. Innate and adaptive immune responses against self-antigen induce the production of autoantibodies and the deposition of immune complexes in tissues. The involvement of the interleukin 17 (IL-17) axis in many inflammatory and autoimmune diseases is now well established, and this has led to the development of successful targeted therapies. Its role in systemic lupus erythematosus (SLE) is less described, since SLE is characterized by the impairment of many other immune actors. Circulating levels of IL-17 are increased in lupus, and tissue staining shows the presence of IL-17-producing cells in organ lesions. Through different mechanisms, the IL-17 axis promotes autoantibody production, immune complex deposition, complement activation and then tissue damage which account for the broad spectrum of clinical manifestations and disease heterogeneity. Although the pathogenesis of SLE remains elusive, from the point of view of the etiology of the occurrence and development of SLE on the molecular level, it can be seen that the imbalance of the immune regulation mechanism plays a key role, especially the imbalance of proinflammatory and anti-inflammatory cytokines. Fcγ receptors (FcɣRs) are expressed in different hematopoietic cells and play a critical role in the regulation of the immune system through immune complex-mediated effector mechanisms. They provide communication between humoral and cellular immune responses and are crucial for regulation of the immune system. Upon interaction with IgG, the activating FcɣR initiate phagocytosis, antibody-dependent cellular cytotoxicity (ADCC), transcription of cytokines genes, and release of inflammatory mediators and are also important in the opsonization of antigens, and in the antigen presentation process. This prospective study included 100 SLE patients, all of them fulfilling the September 2019 European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) diagnosis of SLE, attending the outpatient clinic or the inpatient section at Sohag University Hospital. This study aimed at studying the serum level interleukin-17 (IL-17) levels and Fc gamma receptor (FcγR) in lupus erythematosus patients and to evaluate the association with different clinical presentation, disease activity and laboratory findings. Participants were recruited from the Internal Medicine Department and outpatient clinics of Internal Medicine Department of Sohag University Hospitals. All patients will be subjected to: ▪ Detailed history& clinical examination. ▪ Assessment of disease activity index (SLEDAI): Disease activity will be assessed by using a combination of clinical history, physical examination, organ specific functional tests, and serologic studies. Total SLEDAI score will be measured on the day of serum sample collection. Often it is divided into three categories of scoring: no or mild flare (0 to 3), moderate flare (4-12) and severe (12). ▪ Laboratory investigations: 1. C-reactive protein, Erythrocyte sedimentation rate and Complete blood picture. 2. Blood urea and s.cereatinine. 3. Urine analysis, 24 hrs. protein and urine albumin cereatinine ratio(uACR) 4. Anti-Nuclear Antibody (ANA) and Anti-double stranded DNA (antidsDNA). 5. Abdominal ultrasound. 6. Electrocardiogram (ECG) & echocardiography (Echo). 7. Renal biopsy. Renal biopsies from lupus nephritis (LN) patients will be evaluated according to the revised International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification of lupus nephritis. 8. IL 17 assay by ELISA. 9. FcγR assay by ELISA. The current study included 100 SLE patients with mean age of systemic lupus erythematous was 31.5±6.9 years ranging from 21 to 53 years. With higher percentage of females (87%) among SLE patients. Regarding clinical presentation, severe cases were significantly associated with fever (88.9%), oral ulcer (83.3%), pleural effusion (69.4%), and NPSLE (52.8%), while mild cases were significantly associated with arthralgia (77.8%) (P.<0.05). IL-17 was significantly different between mild, moderate and severe SLE with (p <0.05).Summary 74 FC gamma receptor had significant positive correlation with SLEDAI score (R +ve, P.<0.05). Significant positive correlation between FC gamma receptor and SLEDAI score in all group, as correlation coefficient (r) was positive and P. value <0.05. IL17 had significant positive correlation with ESR, alb/creat ratio, FC gamma receptor (R +ve, P.<0.05). FC gamma receptor had significant positive correlation with ESR, serum creatinine, alb/creat ratio, C3, and AntidsDNA (R +ve, P.<0.05). within all group, IL17 had significant positive correlation with SLEDAI score (R +ve, P.<0.05).). FC gamma receptor had significant positive correlation with SLEDAI score (R +ve, P.<0.05). Significant positive correlation between FC gamma receptor and SLEDAI score in all group, as correlation coefficient (r) was positive and P. value <0.05. The results of this study showing that the IL17 level in discerning moderate/severe from mild cases of SLE are highly significant and indicative of a strong discriminatory power. The results of this study showing that the FC gamma receptor in discerning moderate/severe from mild cases of SLE are highly significant, suggesting a strong discriminatory power. The results of the analysis for the predicted probability of combined biomarkers in discerning moderate/severe from mild cases of SLE are highly significant, suggesting a very strong discriminatory power. indicates that the combined biomarkers have a very high level of accuracy in distinguishing between these two groups. In conclusion, we find association between IL-17 and Fc gamma receptor and SLE which suggests that they have a role in the SLE pathogenesis. Also, IL17 and FC gamma receptor had significant positive correlation with SLE activity indicating their role in activity of SLE. IL-17 was higher in severe cases suggesting that it had also a role in increasing severity of SLE.ConclusionConclusion Conclusion In conclusion, we find that IL17 and FC gamma receptor had significant positive correlation with SLE activity indicating their role in activity of SLE. IL-17 was higher in severe cases sugge. |