Background/Purpose: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by systemic inflammation, autoantibody production, and multiorgan involvement. Although genetic, hormonal, and environmental factors are known contributors to disease development, the role of obesity – a growing epidemic in the United States – remains underexplored in SLE. Evidence suggests that adipose tissue in obese individuals secretes inflammatory mediators, which may influence immune function and disease activity. Our published study showed that a high-fat diet accelerates lupus development and autoimmunity in MRL/lpr lupus-prone mice. Here, we examined immune cell profiles (especially T cell subsets), clinical manifestations, and laboratory parameters in non-obese, overweight, and obese SLE patients to explore the immunometabolic link between obesity and lupus pathogenesis.

Methods: Peripheral blood specimens were collected from 56 consented SLE patients: 15 (27%) non-obese (BMI ≤ 25kg/m2), 12 (21%) overweight (BMI 25-30kg/m2), and 29 (52%) obese (BMI ≥ 30 kg/m2). Multiparameter flow cytometry and serial gating were used to examine immune cell populations in patients’ blood. Clinical data including demographic information, body mass index (BMI), SLE disease activity (SLEDAI), titers of anti-dsDNA antibody, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and complement (C3, C4) levels were extracted from Epic electronic medical record system. Statistical significance and correlation among groups were determined by Student’s t-test and Chi-squared test. Two-tailed p< 0.05 was considered significant.

Results: SLE patients included in this study were 96.4% female, 71.4% African American, 21.4% Caucasian American, 3.6% Asian, and 3.6% Hispanic/Latino. Obese and overweight lupus patients had a significantly higher CRP (p< 0.01) compared to the non-obese patients. The percentage of patients with severe lupus (SLEDAI > 6) was significantly higher in the obese (21.7%) and overweight (8.3%) groups than the non-obese group (0%). In addition, a higher percentage of lupus with skin lesions was found in the obese (27.3%) and overweight (17.9%) groups than the non-obese group (0%). Flow cytometry results revealed a significantly higher frequency of circulating CD4+ T helper cells (especially CCR4+CCR6- Th2 cells and CD4+ICOS+ T follicular helper cells) in obese and overweight lupus patients, compared to non-obese lupus patients (p< 0.05, p< 0.01, respectively). Interestingly, these increased frequencies of circulating Th2 (r=0.8910) and Tfh helper cells (r=0.5902) in obese SLE patients were significantly correlated to SLEDAI level (p< 0.05), whereas the increased levels of complement levels (C3 and C4) in obese SLE patients were closely correlated to patients’ BMI levels (p< 0.05).

Conclusion: Our results showed that obese and overweight lupus patients had an altered Th2 and Tfh cell profile and dysfunctional clinical features with worse outcomes. The increased level of complement is due to obesity, not autoimmunity. Further mechanism studies may provide insight into lupus pathogenesis and treatment strategies for obese SLE patients.

« Back to ACR Convergence 2025

ACR Meeting Abstracts - https://acrabstracts.org/abstract/dissecting-the-role-of-t-cell-subsets-and-complements-in-lupus-pathogenesis-in-systemic-lupus-erythematosus-patients-with-obesity/