Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease resulting from dysregulated innate and adaptive immune components that result in an inflammatory response. Cytokines produced by inflammatory monocytes are increased in SLE patients and signal through the JAK-STAT pathway. SOCS proteins (suppressor of cytokines signaling), specifically SOCS1 and SOCS3 are upregulated by Jak-STAT signallin and then function to limit JAK-STAT signalling. Thus SOCS proteins assure that the JAK-STAT signals are transient and contain the innate and adaptive immune responses. The expression of SOCS proteins in SLE patients has not been assessed. Reports of SOCS1 and SOCS3 mRNA expression in SLE patients are conflicting and have been obtained from whole peripheral blood (PB), thus the cells with dysregulated SOCS expression could not be determined. Our objective was to assess SOCS1 and SOCS3 protein expression in circulating monocytes subsets from SLE patients, and to determine the relationship between SOCS1 and SOCS3 expression and disease activity.
Methods: PB samples were collected from SLE patients and healthy controls through an IRB-approved protocol. American College of Rheumatology or Systemic Lupus International Collaborating Clinics classification criteria for SLE was used to establish diagnosis. Disease activity was determined by using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K 30 Days). PB mononuclear cells (PBMCs) were isolated by red blood cell lysis. PBMCs were stained for flow cytometry to identify classical, intermediate, and non-classical monocytes based on CD14 and CD 16 expression. Intracellular staining was used to evaluate SOCS1 and SOCS3 protein expression in monocyte subsets. Median fluorescence intensities (MFI) for SOCS1 and SOCS3 from SLE patients were compared to healthy patients by one-tailed Mann-Whitney U-test p<0.05. Spearman’s rho correlation was used to test the relationship between SOCS1/3 expression and disease activity, complement proteins (C3 and C4).
Results: Expression of SOCS1 and SOCS3 in monocytes subsets obtained from healthy (n=11) and SLE (n=11) patients were compared. No difference in the monicyre distribution among the subsets was observed between SLE patients and healthy controls. In SLE patients non-classical monocytes showed significantly elevated SOCS1 protein levels (p=0.03) and SOCS1 levelst were positively correlated with disease activity (r=0.56, p=0.04) and negatively correlated with serum C3 (r=-0.56, p=0.04) and C4 (r=-0.79, p=0.003) levels. SOCS3 was also significantly elevated in non-classical monocytes from SLE patients (p=0.01) and negatively correlated with C4 (r=-0.80, p=0.01). The expression of SOCS1 and SOCS3 in classical and intermediate monocytes did not differ between SLE and healthy controls.
Conclusion: In SLE patients SOCS1 is elevated in non-classical monocytes as compared to healtht controls and the levels of SOCS1 in SLE patients correlate with clinical indicators of more active disease. Further studies are needed to determine the role of SOCS1 and SOCS3 in the pathogenesis of SLE and as potential disease activity indicators.
To cite this abstract in AMA style:Khawar T, Cooke J, Daoud N, Sandhu V, Davis W, Peters W, Torralba KMD, Ngo MT, Lezcano S, Payne KJ, Weldon AJ. Suppressor of Cytokine Function One (SOCS1) Is Elevated in Non-Classical Monocytes and Correlates with Disease Activity in Systemic Lupus Erythematosus Patients [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/suppressor-of-cytokine-function-one-socs1-is-elevated-in-non-classical-monocytes-and-correlates-with-disease-activity-in-systemic-lupus-erythematosus-patients/. Accessed December 2, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/suppressor-of-cytokine-function-one-socs1-is-elevated-in-non-classical-monocytes-and-correlates-with-disease-activity-in-systemic-lupus-erythematosus-patients/