HLA alleles as biomarkers of high-titre neutralising antibodies to interferon-ß therapy in multiple sclerosis.
J Med Genet
; 51(6): 395-400, 2014 Jun.
Article
em En
| MEDLINE
| ID: mdl-24748646
ABSTRACT
BACKGROUND:
Recombinant interferon ß (IFNß) is a first-line therapy for relapsing-remitting multiple sclerosis (MS), with a proven effect on the inflammatory activity. Neutralising antibodies against IFNß (NAbs) promote a loss of IFNß 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<20â NU/mL) after 1â year treatment; NAb-titres ≥20â NU/mL were positive tests and NAb titres ≥150â NU/mL in any test were classified as high-titre positives.RESULTS:
The combined presence of DRB1*07/DQA1*02 with A*26 or B*14 was found in 20% of patients with NAbs at high titres, but only in 5.4% of NAb-negative patients (p=0.00052, OR (95% CI) 4.34 (1.85 to 10.13)). The DRB1*0401 allele was also more frequently carried by patients with high titres of NAbs (10% vs 4.5%; p=0.046, OR (95% CI) 2.38 (0.93 to 5.92)). The alleles carried at a significantly lower frequency in patients with high persistent NAbs corresponded to the A*11 allele (3.3% vs 13.8%; p=0.023, OR (95% CI) 0.22 (0.02 to 0.87)), as well as the DRB1*03/DQA1*05/DQB1*02 haplotype (16.3% vs 26.8%; p=0.02, OR (95% CI) 0.53 (0.27 to 1.03)) and the DRB1*13/DQA1*0103/DQB1*0603 haplotype (2.5% vs 9.1%; p=0.045, OR (95% CI) 0.25 (0.03 to 1.02)).CONCLUSIONS:
50% of the studied MS patients carried some of the five independently associated HLA allele/allele combinations described in this work. This relevant percentage of patients could benefit a therapeutic decision.
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Base de dados:
MEDLINE
Assunto principal:
Interferon beta
/
Anticorpos Neutralizantes
/
Cadeias alfa de HLA-DQ
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Cadeias HLA-DRB1
/
Esclerose Múltipla
Limite:
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article