Elevated Serum TGF-β1 Is Linked to Guillain–Barré Syndrome Severity in Bangladeshi Patients: No Association With TGF-β1 −509C/T and +869C/T Polymorphisms

Abstract

Guillain–Barré syndrome (GBS) is an autoimmune peripheral nerve disorder characterized by progressive muscle weakness. Transforming growth factor-beta 1 (TGF-β1) is a major immune-regulating cytokine; therefore, serum concentration of TGF-β1 and its genotypes may contribute to developing GBS. This study is aimed at evaluating the changes in TGF-β1 serum level in GBS and investigating the association of TGF-β1 gene +869C/T and −509C/T) single-nucleotide polymorphisms (SNPs) with GBS susceptibility and TGF-β1 cytokine level. A case–control study was conducted with 200 GBS patients and 200 age-, sex-, and ethnicity-matched healthy controls (HCs). Serum levels of TGF-β1 and anti-GM1 autoantibodies were assessed using enzyme-linked immunosorbent assays. The tetra-primer amplification refractory mutation system-PCR was used to detect the targeted TGF-β1 gene SNPs. In this study, 79% of patients were reported with antecedent events, primarily diarrhea (44%). Overall, 89% of patients were affected with severe GBS; among them, 17% required mechanical ventilation and 21% remained functionally disabled after 6 months. TGF-β1 serum levels were significantly higher in GBS patients compared to HCs (p < 0.0001), demonstrating a cut-off of > 414.02 ng/mL for GBS. In addition, serum levels were correlated to higher GBS-disability scores (r_s = 0.338, p < 0.0001) and were associated with severe GBS (p = 0.04). Elevated TGF-β1 concentration was associated with poor clinical outcomes in patients at 6 months of disease onset (p = 0.006). The TGF-β1-509 T/T genotype was more frequent in Campylobacter jejuni-seropositive patients compared to seronegative patients (OR = 2.87, p_c = 0.04), especially in those with the axonal GBS variant (OR = 3.8, p_c = 0.07). However, no significant associations were found between TGF-β1 SNPs and overall the disease susceptibility or serum TGF-β1 concentration. The study concluded that elevated serum TGF-β1 concentration is associated with both GBS susceptibility and clinical severity and is linked to worse functional outcomes. While the –509 T/T genotype may be linked to C. jejuni–driven axonal GBS, there was no overall polymorphism association with GBS risk or cytokine levels. These findings might be crucial in understanding and predicting disease susceptibility and severity of GBS.