Fc-gamma IIIa-V158F receptor polymorphism contributes to the severity of Guillain-Barré syndrome.

Shoma Hayat,Ishtiaq Mahmud,Zhahirul Islam,Avizit Das,Golap Babu,Zakir Hossain Howlader

doi:10.1002/acn3.51072

Abstract

ObjectiveGuillain‐Barré syndrome (GBS) is a rare, life‐threatening disorder of the peripheral nervous system. Immunoglobulin G Fc‐gamma receptors (FcγRs) mediate and regulate diverse effector functions and are involved in the pathogenesis of GBS. We investigated whether the FcγR polymorphisms FcγRIIa H/R131 (rs1801274), FcγRIIIa V/F158 (rs396991), and FcγRIIIb NA1/NA2, and their haplotype patterns affect the affinity of IgG‐FcγR interactivity and influence GBS susceptibility and severity.MethodsWe determined FcγR polymorphisms in 303 patients with GBS and 302 ethnically matched healthy individuals from Bangladesh by allele‐specific polymerase chain reaction. Pairwise linkage disequilibrium and haplotype patterns were analyzed based on D ´statistics and the genotype package of R statistics, respectively. Logistic regression analysis and Fisher’s exact test with corrected P (Pc) values were employed for statistical comparisons.ResultsFcγRIIIa‐V158F was associated with the severe form of GBS compared to the mild form (P = 0.005, OR = 2.24, 95% CI = 1.28–3.91; Pc = 0.015); however, FcγR genotypes and haplotype patterns did not show any association with GBS susceptibility compared to healthy controls. FcγRIIIa‐V/V158 and FcγRIIIb‐NA2/2 were associated with recent Campylobacter jejuni infection (P ≤ 0.001, OR = 0.36, 95% CI = 0.23–0.56; Pc ≤ 0.003 and P = 0.004, OR = 1.70, 95% CI = 1.18–2.44; Pc ≤ 0.012, respectively). Haplotype 1 (FcγRIIa‐H131R‐ FcγRIIIa‐V158F‐ FcγRIIIb‐NA1/2) and the FcγRIIIb‐NA2/2 genotype were more prevalent among anti‐GM1 antibody‐positive patients (P = 0.031, OR = 9.61, 95% CI = 1.24–74.77, Pc = 0.279; P = 0.027, OR = 1.62, 95% CI = 1.06–2.5, Pc = 0.081, respectively).InterpretationFcγR polymorphisms and haplotypes are not associated with susceptibility to GBS, though the FcγRIIIa‐V158F genotype is associated with the severity of GBS.

Highlights

No significant associations were observed between the FccRIIa, FccRIIIa, and FccRIIIb polymorphisms and susceptibility to Guillain-Barre syndrome (GBS) compared to healthy controls (Table 2)
This study investigated the association of three functionally relevant polymorphisms in Fc-gamma receptors (FccRs) and the resulting haplotype patterns with the susceptibility and severity of GBS among patients compared to healthy controls in a large cohort of GBS in Bangladesh
We found no significant associations between individual FccR alleles or genotypes and susceptibility to GBS; the FccRIIIa-V/ F158 genotype influenced the severity of disease

Summary

Introduction

Guillain-Barre syndrome (GBS) is a post-infectious autoimmune disorder of the peripheral nervous system that can lead to significant morbidity, long-term disability or death.Cross-reactive immune responses induced by molecular mimicry between the outer core structure of infectious agents that trigger GBS and host nerve gangliosides[1] result in a blockade of nerve conduction.[1,2] Campylobacter jejuni has been identified as the predominant causative microbial infectious agent in GBS.[3,4,5] In addition to multifarious microorganism-derived factors, host immunogenic factors are likely to affect GBS susceptibility as only a subset of C. jejuni-infected individuals (1 in 1000–5000 cases) develop GBS.[6,7,8,9] Natural variations in genetic host susceptibility factors have become a focus of research on the susceptibility and severity of disease pathogenesis in GBS.Immunoglobulin G Fc-gamma receptors (FccRs) are important immune-response modulating molecules that link the cellular and humoral immune system by interacting with IgG subtypes (IgG1-4). Cross-reactive immune responses induced by molecular mimicry between the outer core structure of infectious agents that trigger GBS and host nerve gangliosides[1] result in a blockade of nerve conduction.[1,2] Campylobacter jejuni has been identified as the predominant causative microbial infectious agent in GBS.[3,4,5] In addition to multifarious microorganism-derived factors, host immunogenic factors are likely to affect GBS susceptibility as only a subset of C. jejuni-infected individuals (1 in 1000–5000 cases) develop GBS.[6,7,8,9] Natural variations in genetic host susceptibility factors have become a focus of research on the susceptibility and severity of disease pathogenesis in GBS. The most common autoantibodies in GBS are produced against GM1, GD1a a 2020 The Authors.

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