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

ABSTRACT: OBJECTIVE:Guillain-Barré syndrome (GBS) is a rare, life-threatening disorder of the peripheral nervous system. Immunoglobulin G Fc-gamma receptors (Fc?Rs) mediate and regulate diverse effector functions and are involved in the pathogenesis of GBS. We investigated whether the Fc?R polymorphisms Fc?RIIa H/R131 (rs1801274), Fc?RIIIa V/F158 (rs396991), and Fc?RIIIb NA1/NA2, and their haplotype patterns affect the affinity of IgG-Fc?R interactivity and influence GBS susceptibility and severity. METHODS:We determined Fc?R 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. RESULTS:Fc?RIIIa-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, Fc?R genotypes and haplotype patterns did not show any association with GBS susceptibility compared to healthy controls. Fc?RIIIa-V/V158 and Fc?RIIIb-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 (Fc?RIIa-H131R- Fc?RIIIa-V158F- Fc?RIIIb-NA1/2) and the Fc?RIIIb-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). INTERPRETATION:Fc?R polymorphisms and haplotypes are not associated with susceptibility to GBS, though the Fc?RIIIa-V158F genotype is associated with the severity of GBS.

SUBMITTER: Hayat S

PROVIDER: S-EPMC7317642 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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

Hayat Shoma S Babu Golap G Das Avizit A Howlader Zakir Hossain ZH Mahmud Ishtiaq I Islam Zhahirul Z

Annals of clinical and translational neurology 20200602 6

<h4>Objective</h4>Guillain-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 severit ...[more]

PMID: 32484314

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Project description:BackgroundGuillain-Barré syndrome (GBS) is an acute inflammatory neuropathy with a heterogeneous presentation. Although some evidences support the role of autoantibodies in its pathogenesis, the target antigens remain unknown in a substantial proportion of GBS patients. The objective of this study is to screen for autoantibodies targeting peripheral nerve components in Guillain-Barré syndrome.MethodsAutoantibody screening was performed in serum samples from all GBS patients included in the International GBS Outcome study by 11 different Spanish centres. The screening included testing for anti-ganglioside antibodies, anti-nodo/paranodal antibodies, immunocytochemistry on neuroblastoma-derived human motor neurons and murine dorsal root ganglia (DRG) neurons, and immunohistochemistry on monkey peripheral nerve sections. We analysed the staining patterns of patients and controls. The prognostic value of anti-ganglioside antibodies was also analysed.ResultsNone of the GBS patients (n = 100) reacted against the nodo/paranodal proteins tested, and 61 (61%) were positive for, at least, one anti-ganglioside antibody. GBS sera reacted strongly against DRG neurons more frequently than controls both with IgG (6% vs 0%; p = 0.03) and IgM (11% vs 2.2%; p = 0.02) immunodetection. No differences were observed in the proportion of patients reacting against neuroblastoma-derived human motor neurons. Reactivity against monkey nerve tissue was frequently detected both in patients and controls, but specific patterns were only detected in GBS patients: IgG from 13 (13%) patients reacted strongly against Schwann cells. Finally, we confirmed that IgG anti-GM1 antibodies are associated with poorer outcomes independently of other known prognostic factors.ConclusionOur study confirms that (1) GBS patients display a heterogeneous repertoire of autoantibodies targeting nerve cells and structures; (2) gangliosides are the most frequent antigens in GBS patients and have a prognostic value; (3) further antigen-discovery experiments may elucidate other potential antigens in GBS.

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

Publications

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

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