Absence of pathogenic mutations in CD59 in chronic inflammatory demyelinating polyradiculoneuropathy.

Lena Duchateau,Oriol Dols-Icardo,Lorena Martín-Aguilar,Cinta Lleixà,Jordi Diaz-Manera,Jordi Clarimon,Ricard Rojas-Garcia,Ilaria Calegari,Luis Querol,Elba Pascual-Goñi,Laura Cervera-Carles,Andrea Cortese,Isabel Illa,Diego Franciotta,Alfred S Lewin

doi:10.1371/journal.pone.0212647

Abstract

ObjectiveMutations in CD59 cause CIDP-like polyneuropathy in children with inherited chronic hemolysis. We hypothesized that mutations in CD59 might be found in a subset of sporadic CIDP patients.Methods35 patients from two centers, fulfilling the EFNS/PNS diagnostic criteria for CIDP were included. CD59 coding region was amplified by PCR and Sanger sequenced.ResultsOne rare variant was detected in a patient which resulted in a synonymous change and predicted to be neutral. Pathogenic variants were absent in our cohort.InterpretationOur pilot study suggests that mutations in CD59 are absent in adult-onset sporadic CIDP.

Highlights

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare and heterogeneous neurological disorder that is diagnosed according to clinical and electrophysiological diagnostic criteria
Our pilot study suggests that mutations in CD59 are absent in adult-onset sporadic CIDP
These findings strongly suggest that, even though CIDP has an autoimmune pathogenesis, genetic factors could be essential in the development of CIDP in a subset of patients

Summary

Introduction

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare and heterogeneous neurological disorder that is diagnosed according to clinical and electrophysiological diagnostic criteria. The recent description of a significantly increased frequency of the HLA DRB1 15 allele in anti-NF155 antibody-positive patients in comparison with those anti-NF155 antibody-negative, an association that remained hidden before the description of these antibodies, supports this hypothesis [7] These findings strongly suggest that, even though CIDP has an autoimmune pathogenesis, genetic factors could be essential in the development of CIDP in a subset of patients. A non-synonymous homozygous mutation (p.Cys58Tyr) in CD59, a complement inhibitor present in the surface of red blood cells, was discovered in five Jewish children from NorthAfrica with chronic haemolysis and childhood relapsing immune-mediated polyneuropathy [9] Their symptoms were very similar to those of patients suffering from CIDP and the children had a partial response to IVIg and corticosteroid treatment. With the aim of evaluating the possible role of CD59 in CIDP, its coding region was fully sequenced in a homogeneous series of patients who did not present detectable anti-NF155, anti-contactin-1, NF140/186 or CASPR1 autoantibodies

Material and methods

Discussion

Disclosures