Downregulation of SOCS1 gene in the development of Guillain-Barré syndrome

Abstract

Guillain-Barre syndrome (GBS), is a post-infectious disorder of the peripheral nervous system mediated by an aberrant immune response where cytokines play an imperative role in disease pathogenesis. Suppressor of cytokine signaling (SOCS1) proteins, a classical inhibitor of the JAKSTAT signaling pathway, which regulates down-regulates cytokine signaling and suppresses autoimmunity. Therefore, we aimed to determine the association of SOCS1 protein gene expression with GBS immunopathogenesis. This prospective study included 33 GBS patients and 33 healthy controls (HC) in Bangladesh. Detailed clinical investigations and blood samples were collected. Expression of SOCS1 gene was determined by qPCR and measured by using the 2−ΔCT method. Mann-Whitney U-test was performed to measure statistical difference of the 2−ΔCT values among the case and controls. The Pearson correlation was performed to find the association of SOCS1 mRNA expression with the response of regulatory T cells (Tregs) in GBS and healthy individuals. The median age of patients was 31 years (IQR: 22–40), with male predominance (65%). 69% of patients had antecedent events, mostly diarrhea (60 %), and 33% were severely affected. We found significant downregulation of SOCS1 mRNA expression in GBS patients compared to HCs (median: 0.7582 vs. 1.198, P = 0.0463). We also found a statistically insignificant trend of decrease in the expression of SOCS1 mRNA in severe GBS patients compared to mild GBS (median=0.7582 vs. 2.370). However, there were no significant associations between SOCS1 gene expressions and other clinical manifestations of GBS. In addition to that, no significant correlation was found between SOCS1 mRNA expression and CD4+CD25+Tregs, CD4+FOXP3+Tregs, and CD4+CD25+FOXP3+Tregs cell responses in patients with GBS and HCs. Thus, downregulation of the SOCS1 gene may play a pivotal role in developing this autoimmunity in patients with GBS. A large sample size is required to validate the association of the SOCS1 gene with GBS pathogenesis and further clinical progression of the disease.