AB1127 IMPACT OF OVERWEIGHT AND OBESITY ON CLINICAL AND IMMUNOLOGICAL FEATURES IN SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: X. Zhang, R. Quinet, W. Davis, C. Keshavamurthy, J. Zakem, S. Ahrens, S. Shah, D. Reeves, S. Centala, A. Reese, S. Hayat, T. Leeth, S. Umer
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by autoantibodies and systemic inflammation, affecting multiple organs, especially the kieney. Environmental factors, genetic predisposition, and hormones contribute to lupus pathogenesis. One of the environmental factors, obesity, is considered a state of chronic low-grade inflammation and a risk factor for flare in lupus patients. Studies have shown that adipose tissue contributes to a systemic inflammatory state in obese individuals by secreting adipokines, complement components, and other pro-inflammatory mediators. Our recent published data showed that a high-fat diet exacerbated lupus development and autoimmunity in MRL/lpr lupus-prone mice. However, the impact of obesity and overweight on disease activity and clinical features remains unclear. <h3>Objectives:</h3> To investigate the role of obesity in the pathogenesis and autoimmunity in SLE patients by comparing clinical data among obese, overweight, and nonobese lupus patients. <h3>Methods:</h3> We conducted query building in patients diagnosed with SLE (ICD-10 code: M32.9) using AI (Artificial Intelligence) software Deep6 and data abstraction using Slicer Dicer (via EPIC). Thus far we have analyzed a representative sample (n=114) of patients with SLE: BMI, SLE disease activity index (SLEDAI), presence of lupus nephritis, serum creatinine, urine protein/creatinine ratio, level of anti-dsDNA antibody, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and complements (C3 and C4), and lipid profile were extracted from EPIC to Redcap and compared. Unpaired students' t-tests and multi-variable ANOVAs (analysis of variance) were used for statistical significance analysis among the groups. Two-tailed <i>p</i>&lt;0.05 was considered significant. <h3>Results:</h3> 114 SLE patients were included in this study, 48.2% obese, 28.1% overweight, and 23.7% nonobese. Obese/overweight SLE patients had significantly higher triglyceride levels and a higher ratio of total cholesterol/HDL in comparison to nonobese lupus patients (<i>p</i>&lt;0.05). There was no difference in anti-dsDNA levels among the groups. However, the percentage of patients with moderate-severe lupus (SLEDAI ≥6) was higher in the overweight (21.9%) and obese (25.5%) groups than the nonobese (11.1%) group. Significantly higher levels of creatinine (<i>p</i>&lt;0.05), and ESR (<i>p</i>&lt;0.05), and increased incidence of lupus nephritis were noted in obese compared to nonobese lupus patients. Lymphopenia was more often observed in obese/overweight compared to nonobese lupus patients. Significantly higher levels of C3 and a trend toward higher levels of C4 were found in obese (C3 <i>p</i>&lt; 0.005, C4 <i>p</i>=0.0623) and overweight (<i>p</i>&lt;0.05) lupus patients, compared to nonobese lupus patients. <h3>Conclusion:</h3> Obese/overweight lupus patients had increased prevalence of lupus nephritis and elevated serum creatinine, were more likely to have moderate-severe lupus activity and also an altered lipid profile. Further study at cellular and molecular levels in obese lupus patients may help us understand the complex mechanism underlying the relationship between SLE and obesity, providing better preventive and treatment strategies for overweight and obese lupus patients. <h3>REFERENCES:</h3> [1] Tedeschi S, et al. Obesity and the risk of systemic lupus erythematosus among woman in the Nurses' Health Studies. Semi in Arth and Rheu. 2017, 47:376-383 [2] Cozier YC, et al. A prospective study of obesity and risk of systemic lupus erythematosus (SLE) among Black women. Semi in Arth and Rheu. 2019, 48:1030-1034 [3] Zhang X, et al. Lupus pathogenesis and autoimmunity are exacerbated by high fat fiet-induced obesity in MRL/lpr mice. Lupus Sci Med. 2023, 10(1):e000898. doi: 10.1136/lupus-2023-000898. [4] Patterson SL, et al. Obesity is independently associated with worse patient-reported outcome in women with systemic lupus erythematosus. Arthritis Care Res. 2019, 71(1):126-33 [5] Lee YH, et al. Association between circulating leptin levels and systemic lupus erythematosus: an updated meta-analysis. Lupus. 2018, 27 (3): 428-435 <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Xin Zhang This study is funded by a research grant from Collaborative Intramural Research Program (CIRP) supported by Louisiana State University Health Shreveport and Ochsner Clinic Foundation., Robert Quinet: None declared, William Davis: None declared, Chandana Keshavamurthy: None declared, Jerald Zakem: None declared, Samantha Ahrens: None declared, Shivani Shah: None declared, Douglas Reeves: None declared, Sneha Centala: None declared, Alexandra Reese: None declared, Samina Hayat: None declared, Teresa Leeth: None declared, Sarwat Umer: None declared.