Background/Purpose: Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease characterized by autoantibodies and disruption of multiple organs due to immunomodulatory dysfunction. Obesity is a prevalent and persistent epidemic that affects more than 31% of the US population. Obesity is well-known as a risk factor for autoimmune disease and considered to cause a chronic inflammatory status. Our recent published studies showed that a high-fat diet exacerbated lupus development and autoimmunity in MRL/lpr lupus-prone mice. Here, we examined the immune cell profiles and the clinical features in non-obese, overweight, and obese lupus patients.

Methods: Blood specimens were collected from 41 consented SLE patients: 10 (24%) non-obese (BMI ≤ 25kg/m2), 8 (20%) overweight (BMI 25-30kg/m2), and 23 (56%) obese (BMI ≥ 30 kg/m2). Multiparameter flow cytometry and serial gating were used to examine immune cell populations in peripheral blood mononuclear cells (PBMCs). Clinical data including demographic information, body mass index (BMI), SLE disease activity (SLEDAI), titers of anti-dsDNA antibody, serum creatinine, urine protein/creatinine ratio, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and complement 3 & 4 (C3, C4) levels were extracted from Epic electronic medical record (EMR) system. Lipid profiles of lupus patients were determined by clinical lab.  Unpaired Student’s t-test and multi-variable ANOVA were used for statistical significance analysis among the groups. Two-tailed p< 0.05 was considered significant.  

Results: SLE patients included in this study were 95% female, 71% African American, 22% Caucasian American, 5% Asian, and 2% Hispanic/Latino. Obese lupus patients had a significantly lower level of high-density lipoprotein (HDL) and higher ratio of total cholesterol/HDL, compared to the non-obese patients and overweight patients. Although there is no difference in anti-dsDNA antibody levels among groups, the percentage of patients with severe lupus (SLEDAI > 6) was significantly higher in the obese (26.3%) and overweight (16.3%) groups than the nonobese group (0%). Flowcytometry results revealed a significantly lower frequency of CD8+ T cells and 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). A lower frequency of CXCR3+CCR6- Th1 cells was also found in obese and overweight lupus patients, but there was no difference of Th17 cells among the groups. Clinically, significantly higher levels of urine protein/creatinine ratio (p< 0.05), CRP (p< 0.005), and ESR (p< 0.05) were noted in obese patients compared to non-obese lupus patients.  

Conclusion: Our results showed that obese and overweight lupus patients had an altered Th2/T follicular helper cell dominant immune cell profile and dysfunctional clinical features with worse outcomes. Further study of the association of these immune cells and their cytokines with serologic and clinical outcomes in obese lupus patients may help us understand the complex mechanism underlying the relationship between SLE and obesity. 

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/landscape-of-immune-cells-and-autoimmunity-in-systemic-lupus-erythematosus-patients-with-obesity/