Background: IFN-β is widely used as the first-line disease-modifying treatment for multiple sclerosis. However, 30-50% of multiple sclerosis patients do not respond to this therapy. Identification of genetic variants and their combinations that predict responsiveness to IFN-β could be useful for treatment prognosis.
Materials & methods: The combinations of alleles of nine polymorphic loci in immune-response genes were analyzed in 253 Russian multiple sclerosis patients as possible determinants of clinically optimal IFN-β treatment response using APSampler software.
Results: Carriage of TGFB1*-509C (cytokine= a protein that inhibits certain immune function) and CCR5*d (chemokine=chemotactic cytokine= a protein that attracts certain cell type=perfume for cells) was associated with favorable IFN-β response by itself. CCR5*d, IFNAR1*16725G (Interferon alpha receptor) , IFNG*874T (interferon gamma = anti-viral cytokine that activates macrophages) and IFNB1*153T/T (interferon beta = anti-viral cytokine) were the components of the combinations, associated with clinically optimal response to IFN-β. Carriage of composite markers (CCR5*d + IFNAR1*G + IFNB1*T/T) or (CCR5*d + IFNAR1*G + IFNG*T) is beneficial for IFN-β treatment efficacy.
Discussion: The data obtained provides evidence of the cumulative effect of immune-response genes on IFN-β treatment efficacy. This joint contribution may reflect the additive effect of independent allelic variants (genetic varinats) and epistatic (variants that are produced after the genetic variants are produced) interactions between some of them.
Beta Interferons have showed limited efficacy in a significant number of MSers, but historically there was no incentive to pharma to work out which person would respond and those who would not. This is because pharma wanted everyone on and paying for the drug.
Many Msers develop neutralising antibodies to beta interferons and this stops them working. Again pharma did not appear to be interested. However with the advent of more active drugs, pharma have begun to come around and take an interest. If you remove the MSers who neutralise the beta interferon then they appear to work much more and to a level of the second generation of DMT, so there is an interest in neutralizing antibodies now.
The ability to respond to any drug is determined by the genetic make-up. Analysing the genes to see how genetic variants will impinge on drug action is called Pharmacogenomics. This study identify some related to beta interferon. Pharma have no doubt done a lot more and there are other studies on this. We need to Pharmacogenomics on Lemtrada to work out which people get antibody-induced autoimmunities.