HLA-A2 and B35 as strong predictors of responsiveness to clozapine in a sample of Italian schizophrenic patients

Abstract

Clinical response to immunomodulatory therapies in multiple sclerosis (MS) is variable among patients. Currently, there are no validated biomarkers of clinical response to any of the approved treatments for MS. The objective of this study was to determine if HLA-class II alleles predict the clinical response to glatiramer acetate (GA).This was a prospective study of 64 MS patients with relapsing-remitting disease. Patients were HLA-typed and classified as GA-responders or non-responders after 2 years of treatment based on a clinical criterion. Statistical models were used to determine whether HLA-DR and DQ alleles and haplotypes predict the clinical response to GA.Tests of association of response singled out four alleles and two haplotypes with nominal p<0.01. The presence of alleles DR15 or DQ6 or the absence of DR17 and DQ2 alleles was associated with favorable clinical response. The presence of the DR15−DQ6 haplotype and the absence of the DR17–DQ2 haplotype were also associated with favorable treatment response. A best fitting two-haplotype model resulted in the identification of three prognostic categories (good, neutral, and poor). A DR15-DQ6 positive but DR17-DQ2 negative combination was strongly predictive of a favorable clinical response (71%). Conversely, a DR15-DQ6 negative but DR17-DQ2 positive combination was strongly predictive of poor clinical response to GA (17%).HLA-DR and DQ typing may prove to be useful biomarkers of predicting response to GA in MS and may help select patients appropriate for this treatment.