Genetic Biomarkers for Intravenous Immunoglobulin Response in Chronic Inflammatory Demyelinating Polyradiculoneuropathy

Overview

Journal Eur J Neurol

Publisher Wiley

Specialty Neurology

Date 2021 Jan 18

PMID 33460483

Citations 5

Authors

Krista Kuitwaard

Pieter A van Doorn

Thiziri Bengrine

Wouter van Rijs

Frank Baas

Sietse Q Nagelkerke

Taco W Kuijpers

Willem-Jan R Fokkink

Carina Bunschoten

Merel C Broers

Sten P Willemsen

Bart C Jacobs

Ruth Huizinga

Affiliations

Soon will be listed here.

Abstract

Background And Purpose: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a clinical and electrophysiological heterogeneous immune-mediated polyneuropathy. Intravenous immunoglobulin (IVIg), corticosteroids, and plasma exchange are proven effective treatments for CIDP. The clinical response to IVIg is variable between patients and currently unexplained. Finding biomarkers related to treatment response can help to understand the diversity of CIDP and personalise treatment choice.

Methods: We investigated whether genetic variation between patients may explain some of these differences in treatment response. Based on previous publications, we selected six candidate genes that might affect immune and axonal functions, IVIg metabolism, and treatment response in CIDP. Genetic variants were assessed in 172 CIDP patients treated with at least one course of IVIg (2 g/kg). A response to IVIg was defined by ≥1 grade improvement on the modified Rankin Scale. Blood samples were tested for variations in CNTN2, PRF1, FCGRT, FCGR2B, GJB1, and SH2D2A genes.

Results: In univariate analysis, patients with the FCGR2B promoter variant 2B.4/2B.1 responded more often to IVIg than patients with the 2B.1/2B.1 variant (odds ratio [OR] = 6.9, 95% confidence interval [CI] = 1.6-30; p = 0.003). Patients with the p.(Ala91Val) variant of PRF1 were less often IVIg responsive (OR = 0.34, 95% CI = 0.13-0.91; p = 0.038). In multivariate analysis, both PRF1 and FCGR2B showed discriminative ability to predict the chance of IVIg response (area under the curve = 0.67).

Conclusions: Variations in PRF1 and the promoter region of FCGR2B are associated with the response to IVIg in CIDP. These findings, which require validation, are a first step towards the understanding of the heterogeneity in the treatment response in CIDP.

Citing Articles

Association of the neonatal Fc receptor promoter variable number of tandem repeat polymorphism with immunoglobulin response in patients with chronic inflammatory demyelinating polyneuropathy.

Fisse A, Schafer E, Hieke A, Schroder M, Klimas R, Brunger J Eur J Neurol. 2024; 31(4):e16205.

PMID: 38205888 PMC: 11235998. DOI: 10.1111/ene.16205.

Chronic Inflammatory Demyelinating Polyneuropathy and Evaluation of the Visual Evoked Potentials: A Review of the Literature.

Tsoumanis P, Kitsouli A, Stefanou C, Papathanakos G, Stefanou S, Tepelenis K Medicina (Kaunas). 2023; 59(12).

PMID: 38138263 PMC: 10744621. DOI: 10.3390/medicina59122160.

Efficacy and Safety of Intravenous Immunoglobulin Treatment in Selected Neurological Diseases-One Centre's Experience Based on the Therapy of 141 Patients.

Lasek-Bal A, Wagner-Kusz A, Rogoz B, Cisowska-Babraj M, Gajewska G J Clin Med. 2023; 12(18).

PMID: 37762922 PMC: 10531894. DOI: 10.3390/jcm12185983.

[Prognostic and monitoring biomarkers in chronic inflammatory demyelinating polyneuropathy].

Llaurado A, Sanchez-Tejerina D, Vidal-Taboada J, Salvado M, Sotoca J, Juntas-Morales R Rev Neurol. 2022; 74(7):232-241.

PMID: 35332927 PMC: 11502160. DOI: 10.33588/rn.7407.2021495.

Update on Intravenous Immunoglobulin in Neurology: Modulating Neuro-autoimmunity, Evolving Factors on Efficacy and Dosing and Challenges on Stopping Chronic IVIg Therapy.

Dalakas M Neurotherapeutics. 2021; 18(4):2397-2418.

PMID: 34766257 PMC: 8585501. DOI: 10.1007/s13311-021-01108-4.

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