Abstract
Guillain-Barré syndrome (GBS) is an autoimmune disorder of the peripheral nervous system triggered by molecular mimicry between pathogen lipopolysaccharides and host nerve gangliosides. Polymorphisms in the Fas receptor (FAS) and Fas ligand (FASL) genes may potentially alter the elimination of autoreactive immune cells and affect disease susceptibility or disease severity in GBS. We detected single nucleotide polymorphisms (SNPs) in FAS (-1377G/A and -670A/G) and FASL (-843C/T) in a prospective cohort of 300 patients with GBS and 300 healthy controls from the Bangladeshi population. Genotype distributions were not significantly different between patients with GBS and healthy controls. The FAS -670 AG heterozygous (P = 0.0005, OR = 2.5, 95% CI = 1.5–4.2) and GG homozygous (P = 0.0048, OR = 2.6, 95% CI = 1.3–5.0) genotypes were more common in patients with anti-GM1 antibodies than patients without anti-GM1 antibodies. The FAS -670 G allele was more prevalent in anti-GM1 antibody-positive than -negative patients (P = 0.0002, OR = 1.9, 95% CI = 1.4–2.7) and also in patients with the axonal subtype than demyelinating subtype (P < 0.0001, OR = 4.8, 95% CI = 2.3–10.1). The 1377G/-670G GG haplotype was significantly associated with the axonal subtype (P < 0.0001) and anti-ganglioside antibody-positivity (P = 0.0008) in GBS. Serum sFas (237.5 pg/mL vs. 159.5 pg/mL; P < 0.0001) and sFasL (225.1 pg/mL vs. 183.4 pg/mL; P = 0.0069) were elevated in patients with GBS compared to healthy controls, and among patients with high serum sFas was associated with severe GBS (P = 0.0406). In conclusion, this study indicates FAS-FASL promoter SNPs may promote the production of cross-reactive anti-ganglioside antibodies in GBS.
Highlights
IntroductionFas receptor (FAS) polymorphisms and soluble Fas (sFas) and GBS in Bangladesh of Bangladesh, Global Affairs Canada (GAC), the Swedish International Development Cooperation Agency (Sida), and the Department for International Development, UK (DFID), for endowing with unrestricted support
Fas-Fas ligand (FasL) play a crucial role in elimination of inflammatory immune cells from the nervous system and are implicated in several neurodegenerative diseases [25,26,27], Fas receptor (FAS)-Fas ligand (FASL) genotypes may affect susceptibility and disease severity
Patients with GBS had significantly elevated serum soluble Fas (sFas) and sFasL levels, though no associations were observed between sFas or sFasL levels and the various genotypes of the single nucleotide polymorphisms (SNPs) studied
Summary
FAS polymorphisms and sFas and GBS in Bangladesh of Bangladesh, Global Affairs Canada (GAC), the Swedish International Development Cooperation Agency (Sida), and the Department for International Development, UK (DFID), for endowing with unrestricted support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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