HLA class II and response to interferon-beta in multiple sclerosis

Epidemiological studies and genome screeningssuggest that genetic factors influence susceptibilityto multiple sclerosis (MS). The genomic region thatcodes for the major histocompatibility complex(MHC) has been most consistently associated withMS (1–3). The human leucocyte antigen (HLA)class II DR2 haplotype (DRB1*1501,DQA1*0102, DQB1*0602) has been associatedwith MS in Caucasians (1–5), including patientsfrom our geographical area (6). The association ofDR2 with some clinical characteristics possiblyrelated to disease severity (female sex, younger ageat onset) has been reported. However, other studiesemploying larger numbers of patients have gener-ally failed to show any significant effect of HLA ondisease course or outcome among Europeans (7).Thus, the pathogenic role of HLA in MS remainsto be elucidated, particularly its relationship to theresponse to immunomodulatory therapies.Interferon-beta(IFN-b)hasprovedtobeeffectivefor the treatment of MS in the relapsing–remitting(RR) and secondary progressive (SP) phases inpatients still experiencing relapses. IFN-b reducesthe attack rate and probably slows the sustainedprogression of disability (8). However, nearly 30%ofpatientseither failtorespondorrespondsubopt-imally to this treatment as currently administered(9). Patients with increased or unchanged diseaseactivity, either due to relapses or to gradual disabil-ity progression, should be considered as non-responders or suboptimal responders (10).Prognostic markers, either clinical or genetic, areneeded for the early discrimination of IFN-bresponders from non-responders to help improvetreatment options for individual patients. Toinvestigate prognostic markers of the response toIFN-b therapy we therefore assessed the possiblerelationship between treatment response and HLAclass II allele distribution.