Session Title: SLE – Clinical Poster I: Epidemiology & Pathogenesis
Session Type: Poster Session (Sunday)
Session Time: 9:00AM-11:00AM
Background/Purpose: Systemic lupus erythematosus (SLE) is a autoimmune disease characterized by deregulated cytokine production. IL-23 bridges innate and adaptive immunity by inducing the differentiation of T cells into pro-inflammatory Th17. We have previously shown that IL-23 is upregulated in SLE patients and lupus prone mice. Besides inducing the generation of Th1, we found that in lupus, IL-23 promotes the generation of T follicular helper cells (Tfh) and inhibits regulatory T cells, thus increasing production of anti-dsDNA antibodies. Aim of this study was to evaluate IL-23 levels and its association with various clinical and laboratory parameters of SLE.
Methods: Serum IL-23 was measured in 56 SLE patients by ELISA (54 females and 2 males; age:42±12years; racial distribution:43% white, 28% African-American,20% Asian, 8% other). Institutional IRB approved the study. Disease activity was measured by SLEDAI (0-34; mean±sem= 6.71±1.02). 55% of patients were on prednisone at a mean dose of 11.09 mg (1–60). Other medications included hydroxychloroquine (67%), mycophenolate mofetil (34%), azathioprine (10%). Two patients were on IV cyclophosphamide, 3 on belimumab, 1 on tacrolimus, 1 on tocilizumab. STATA was used for statistical analyses: non-paired t-test and Pearson’s correlation. Multiple linear regression analysis was used to analyze the effect of SLEDAI and medications on IL-23 expression.
Results: IL-23 levels in the serum of SLE patients were significantly higher in patients with active disease as measured by the SLEDAI (r=0.4363, p=0.0008). Correlation persisted even when we excluded the dsDNA and complement components from the SLEDAI, defined as clinical SLEDAI (r=0.3752, p=0.0044). Serum IL-23 was strongly correlated with skin (r=0.2853; p=0.03), renal (r=0.2928; p=0.0286) domains of SLEDAI and arthritis (p=0.03).There was no correlation with neurological manifestations or presence of serositis. IL-23 levels had significant positive correlation with anti-dsDNA (p=0.005) and negative with complement C3 (p=0.0003). We found no relationship between patients’ demographics, prior disease manifestations or other autoantibody profile or cytopenias. Of note, SSA+ patients had a non-statistically significant trend for higher IL-23 levels than SSA- patients (p=0.065). Multivariate regression analysis was used to account for potential confounding effect of medications on the correlation of SLEDAI and IL-23 levels. We found that IL-23 levels strongly correlate with SLEDAI after controlling for dose and type of medications including prednisone dose (p< 0.001).
Conclusion: In this cross-sectional analysis of SLE patients we found that IL-23 levels track disease activity and correlate with renal, skin and musculoskeletal manifestations but not with cytopenias or serositis. This is in line with murine data where blocking IL-23 ameliorated both kidney and skin disease. No immunomodulatory medication seems to be affecting IL-23 levels suggesting that current medications used in SLE are not as effective in shutting down the IL-23/IL-17 axis. Furthermore, our data suggest that IL-23 inhibitors may be helpful not only in non-renal SLE, where they are currently being tested, but also in lupus nephritis.
To cite this abstract in AMA style:Vukelic M, Laloo A, Kyttaris V. Elevated Serum Interleukin-23 Level in Patients with Systemic Lupus Erythematosus Is Associated with Disease Activity, Clinical and Immunological Markers [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/elevated-serum-interleukin-23-level-in-patients-with-systemic-lupus-erythematosus-is-associated-with-disease-activity-clinical-and-immunological-markers/. Accessed June 24, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/elevated-serum-interleukin-23-level-in-patients-with-systemic-lupus-erythematosus-is-associated-with-disease-activity-clinical-and-immunological-markers/