Genetic and infectious profiles influence cerebrospinal fluid IgG abnormality in Japanese multiple sclerosis patients.

Satoshi Yoshimura,Shinya Sato,Katsuhisa Masaki,Hirofumi Ochi,Yuji Kawano,Takuya Matsushita,Noriko Isobe,Jun-Ichi Kira,Akio Suzumura

doi:10.1371/journal.pone.0095367

Satoshi Yoshimura, Shinya Sato + Show 7 more

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https://doi.org/10.1371/journal.pone.0095367

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Journal: PloS one	Publication Date: Apr 15, 2014
Citations: 37	License type: CC BY 4.0

Affiliation: Kyushu University, Ehime University

Abstract

BackgroundAbnormal intrathecal synthesis of IgG, reflected by cerebrospinal fluid (CSF) oligoclonal IgG bands (OBs) and increased IgG index, is much less frequently observed in Japanese multiple sclerosis (MS) cohorts compared with Western cohorts. We aimed to clarify whether genetic and common infectious backgrounds influence CSF IgG abnormality in Japanese MS patients.MethodologyWe analyzed HLA-DRB1 alleles, and IgG antibodies against Chlamydia pneumoniae, Helicobacter pylori, Epstein-Barr virus nuclear antigen (EBNA), and varicella zoster virus (VZV) in 94 patients with MS and 367 unrelated healthy controls (HCs). We defined CSF IgG abnormality as the presence of CSF OBs and/or increased IgG index (>0.658).Principal FindingsCSF IgG abnormality was found in 59 of 94 (62.8%) MS patients. CSF IgG abnormality-positive patients had a significantly higher frequency of brain MRI lesions meeting the Barkhof criteria compared with abnormality-negative patients. Compared with HCs, CSF IgG abnormality-positive MS patients showed a significantly higher frequency of DRB1*1501, whereas CSF IgG abnormality-negative patients had a significantly higher frequency of DRB1*0405. CSF IgG abnormality-positive MS patients had a significantly higher frequency of anti-C. pneumoniae IgG antibodies compared with CSF IgG abnormality-negative MS patients, although there was no difference in the frequency of anti-C. pneumoniae IgG antibodies between HCs and total MS patients. Compared with HCs, anti-H. pylori IgG antibodies were detected significantly less frequently in the total MS patients, especially in CSF IgG abnormality-negative MS patients. The frequencies of antibodies against EBNA and VZV did not differ significantly among the groups.ConclusionsCSF IgG abnormality is associated with Western MS-like brain MRI features. DRB1*1501 and C. pneumoniae infection confer CSF IgG abnormality, while DRB1*0405 and H. pylori infection are positively and negatively associated with CSF IgG abnormality-negative MS, respectively, suggesting that genetic and environmental factors differentially contribute to MS susceptibility according to the CSF IgG abnormality status.

Highlights

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) with a supposed autoimmune origin involving T and B cells [1]
DRB1*1501 and C. pneumoniae infection confer cerebrospinal fluid (CSF) IgG abnormality, while DRB1*0405 and H. pylori infection are positively and negatively associated with CSF IgG abnormality-negative multiple sclerosis (MS), respectively, suggesting that genetic and environmental factors differentially contribute to MS susceptibility according to the CSF IgG abnormality status
In the Japanese population, we and others reported that conventional MS (CMS) is associated with HLA-DRB1*1501, while opticospinal MS (OSMS) is associated with HLA-DPB1*0501 [4,5], but no associations were found with any HLA class I alleles [6]

Summary

Introduction

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) with a supposed autoimmune origin involving T and B cells [1]. In Caucasians, the HLA-DRB1*1501 allele is most strongly associated with MS, whereas the class I allele HLA-. In the Japanese population, we and others reported that conventional MS (CMS) is associated with HLA-DRB1*1501, while opticospinal MS (OSMS) is associated with HLA-DPB1*0501 [4,5], but no associations were found with any HLA class I alleles [6]. We reported that HLA-DRB1*0405 and HLA-DPB1*0301 are susceptibility alleles, while DRB1*0901 and DPB1*0401 are protective alleles for Japanese MS when neuromyelitis optica (NMO) and NMO spectrum disorder (NMOSD) patients are excluded [7]. Abnormal intrathecal synthesis of IgG, reflected by cerebrospinal fluid (CSF) oligoclonal IgG bands (OBs) and increased IgG index, is much less frequently observed in Japanese multiple sclerosis (MS) cohorts compared with Western cohorts. We aimed to clarify whether genetic and common infectious backgrounds influence CSF IgG abnormality in Japanese MS patients

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