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

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.

The weaker-binding Fc γ receptor IIIa F158 allotype retains sensitivity to N-glycan composition and exhibits a destabilized antibody-binding interface

“…Data from primary human NK cells also supports V158 promoting ADCC compared to F158 (7). Clinical studies link the F158 allotype to increased susceptibility to a wide assortment of diseases (10)(11)(12)(13)(14). Furthermore, V158 patients experienced superior responses to clinical antibody treatments (15)(16)(17).…”

“…Next, 100 mg/L [ 15 N]-lysine, [ 15 N]-phenylalanine and [ 15 N]-tyrosine were added. For NMR experiments utilizing 13 C, the medium was supplemented with 3 g/L [ 13 CU]glucose. pH was adjusted to 7.20 before adjusting osmolarity with 5 M NaCl to 260-280 mOsm/kg, followed by a final adjustment of pH to 7.20.…”

“…Direct 13 C observe experiments were collected with the hxinepph pulse sequence, with 16384 and 128 complex points in the direct and indirect dimensions, respectively. The Bruker hsqcetfpf3gpsi2 pulse sequence was used to collect 1 H-15 N correlations with 1024 and 256 complex points in the direct and indirect dimensions, respectively.…”

Genetic Markers and Predictive Factors Influencing the Aggressive Behavior of Cerebral Cavernous Malformation

“…This polymorphism is capable to increase the binding affinity of FCGR2A to IgG, resulting in activation of the FCGR2A signaling pathway and upregulation of IgG2-dependent phagocytosis 39,40 . The GG genotype has been associated with several autoimmune diseases, such as Systemic Lupus Erythematosus, Type 1 Diabetes Mellitus, Crohn's Disease and others, based on its relationship with the release and stimulation of responsive inflammatory processes 41 . Protein structure prediction using bioinformatic tools is an important approach to understand the FCGR2A variants.…”

CRISPR typing of Campylobacter jejuni reveals a link between CRISPR array preservation and Guillain-Barré syndrome

“…However, not all C. jejuni-infected individuals develop GBS after enteritis 6 . In addition to host susceptibility factors [7][8][9][10] , bacterial virulence factors also function as key regulatory elements that may trigger GBS [11][12][13] . Moreover, the cst-II sialyltransferase gene of C. jejuni, which encodes ganglioside-like structures expressed on the bacterial cell surface, has been linked to GBS 14 .…”