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Mult Scler. 2015 Aug;21(9):1104-11. doi: 10.1177/1352458514556302. Epub 2014 Nov 12.

A new risk variant for multiple sclerosis at the immunoglobulin heavy chain locus associates with intrathecal IgG, IgM index and oligoclonal bands.

Author information

1
Unidad de Esclerosis Múltiple, Hospital Universitario Virgen Macarena, Sevilla, Spain/These authors contributed equally to this work.
2
Departamento de Biología Celular e Inmunología, Instituto de Parasitología y Biomedicina López Neyra (IPBLN), Consejo Superior de Investigaciones Científicas CSIC, 18016 Granada, Spain/These authors contributed equally to this work lindo@ipb.csic.es.
3
Departamento de Biología Celular e Inmunología, Instituto de Parasitología y Biomedicina López Neyra (IPBLN), Consejo Superior de Investigaciones Científicas CSIC, 18016 Granada, Spain.
4
Unidad de Esclerosis Múltiple, Hospital Universitario Virgen Macarena, Sevilla, Spain.
5
Unidad de Gestión Clínica de Neurociencias, Instituto de Biomedicina de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Málaga, Spain.
6
Servicio de Neurología, Hospital Virgen de las Nieves, Granada, Spain.
7
Centro Regional de Transfusión Sanguínea Granada-Almería, Ganada, Spain.
8
Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain.
9
Centro Andaluz de Estudios Bioinformáticos (CAEBi), Sevilla, Spain.
10
Hospital Ramon y Cajal, Departments of Immunology and Neurology, MS Unit, (IRYCIS), Madrid, Spain.
11
Multiple Sclerosis Unit, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
12
ImmunologyDepartment, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico S. Carlos (IdISSC), Madrid, Spain.
13
Servicio de Biología Molecular, Hospital Universitario Virgen Macarena, Facultad de Medicina, Sevilla, Spain/These authors contributed equally to this work.

Abstract

BACKGROUND:

Recent findings have shown a correlation between the intrathecal IgG index and variants at the immunoglobulin heavy chain (IGHC) locus in patients with multiple sclerosis (MS).

OBJECTIVES:

The objective of this paper is to analyse the association of the locus with MS susceptibility and its relationship with intrathecal immunoglobulin (Ig) parameters.

METHODS:

We genotyped the rs11621145 variant, located at the IGHC locus, in 2726 patients with MS and 2133 healthy controls. Associations of intrathecal IgG and IgM indexes with rs11621145 were analysed by linear regression analysis in 538 MS patients.

RESULTS:

We found that rs11621145 showed statistically significant evidence for association with susceptibility to MS (odds ratio = 0.69, p = 1.053E-09), though validation of this result in additional cohorts would be desirable. We confirmed the association between the IgG index and the rs11621145 (p = 6.85E-07, Beta = 0.207). Furthermore, rs11621145 was inversely correlated with IgM index (p = 7.24E-04, Beta = -0.277), and therefore marks a decreased likelihood of presenting IgM oligoclonal bands (odds ratio = 0.38, p = 2.35E-06).

CONCLUSIONS:

Our results suggest that the polymorphism of the IGHC locus could be altering the switching of the Ig isotype in B cells and it may be interfering with T-dependent and T-independent antibody responses.

KEYWORDS:

Multiple sclerosis (MS); SNP variant; association; immunoglobulin heavy chain (IGHC) locus; intrathecal IgG/IgM index; oligoclonal bands (OCBs)

PMID:
25392328
DOI:
10.1177/1352458514556302
[Indexed for MEDLINE]
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