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Complex traits
ORIGINAL ARTICLE
HLA alleles as biomarkers of high-titre neutralising antibodies to interferon-β therapy in multiple sclerosis Concepción Núñez,1 Mª Carmen Cénit,1 Roberto Alvarez-Lafuente,2 Jordi Río,3 Miguel Fernández-Arquero,1 Rafael Arroyo,2 Xavier Montalbán,3 Oscar Fernández,4 Begoña Oliver-Martos,5 Laura Leyva,5 Manuel Comabella,3 Elena Urcelay1 ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ jmedgenet-2014-102348). For numbered affiliations see end of article. Correspondence to Dr Elena Urcelay, Immunology Department, Hospital Clínico San Carlos, IdISSC, Martin Lagos s/n, Madrid 28040, Spain; elena.urcelay@salud. madrid.org, eurcelay.hcsc@ salud.madrid.org CN and MCC contributed equally. Received 10 February 2014 Accepted 6 March 2014 Published Online First 19 April 2014
ABSTRACT Background Recombinant interferon β (IFNβ) is a first-line therapy for relapsing-remitting multiple sclerosis (MS), with a proven effect on the inflammatory activity. Neutralising antibodies against IFNβ (NAbs) promote a loss of IFNβ bioactivity in a titre-dependent way and their development was associated with certain human leucocyte antigen (HLA) alleles. We investigated the contribution conferred by HLA alleles on the development of NAbs in independent cohorts of Southern Europe. Methods Serum NAbs from 610 MS patients with HLA-genotype data were evaluated by cytopathic effect assay: negative tests included at least one negative result (NAb titres
Complex traits
ORIGINAL ARTICLE
HLA alleles as biomarkers of high-titre neutralising antibodies to interferon-β therapy in multiple sclerosis Concepción Núñez,1 Mª Carmen Cénit,1 Roberto Alvarez-Lafuente,2 Jordi Río,3 Miguel Fernández-Arquero,1 Rafael Arroyo,2 Xavier Montalbán,3 Oscar Fernández,4 Begoña Oliver-Martos,5 Laura Leyva,5 Manuel Comabella,3 Elena Urcelay1 ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ jmedgenet-2014-102348). For numbered affiliations see end of article. Correspondence to Dr Elena Urcelay, Immunology Department, Hospital Clínico San Carlos, IdISSC, Martin Lagos s/n, Madrid 28040, Spain; elena.urcelay@salud. madrid.org, eurcelay.hcsc@ salud.madrid.org CN and MCC contributed equally. Received 10 February 2014 Accepted 6 March 2014 Published Online First 19 April 2014
ABSTRACT Background Recombinant interferon β (IFNβ) is a first-line therapy for relapsing-remitting multiple sclerosis (MS), with a proven effect on the inflammatory activity. Neutralising antibodies against IFNβ (NAbs) promote a loss of IFNβ bioactivity in a titre-dependent way and their development was associated with certain human leucocyte antigen (HLA) alleles. We investigated the contribution conferred by HLA alleles on the development of NAbs in independent cohorts of Southern Europe. Methods Serum NAbs from 610 MS patients with HLA-genotype data were evaluated by cytopathic effect assay: negative tests included at least one negative result (NAb titres
