Allelic Combinations of Immune-Response Genes as Possible Composite Markers of IFN-β Efficacy in Multiple Sclerosis Patients

Abstract

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 and epistatic interactions between some of them.

Immune response genes receptors expression and polymorphisms in relation to multiple sclerosis susceptibility and response to INF‐β therapy

“…This disagrees with Pulkkinen et al , reported an increased frequency of CCR5 Δ32/Δ32 genotype in MS patients compared with controls. However, in our study, carriage of CCR5 Δ32 allele was associated with a good response to IFN‐β therapy ( P ≤ 0.01), which is in line with a study done by Kulakova et al , they found that CCR5Δ32 allele was correlated with a favorable IFN‐β and an adverse GA responses, thus they could be used as selection tools for the best line of treatment and chemokine system interference might be an effective therapeutic approach in MS.…”

“…Regarding the effect of type 1 interferon receptors polymorphisms on the response to IFN‐β treatment, the genomic variations of IFNAR1 and IFNAR2 genes were not associated with IFN‐β treatment response which were consistent with other previous studies .…”

“…One of the important mechanisms of action of IFN‐β in MS treatment is its ability to decrease the permeability of the blood–brain barrier to the activated lymphocytes and monocytes by inhibiting adhesion molecules and matrix metalloproteinases. Deletion of 32 bp in CCR5 gene mimic this action by producing nonfunctional protein, decreasing the chemotaxis of autoreactive T cells into the CNS .…”

“…Biomarkers used for providing a priority treatment choice for an individual patient are thought to be genetic variants affecting the clinical response to the drugs . Only few studies tried to examine the relationship between IFN‐β treatment efficacy and IFNAR1 and IFNAR2 and CCR5 genes polymorphisms with variable results . However, there was no study in the literature exploring the effect of these polymorphisms in Egyptian patients.…”

Efficacy of Synthetic Peptide Corresponding to the ACTH-Like Sequence of Human Immunoglobulin G1 in Experimental Autoimmune Encephalomyelitis

“…Glatiramer acetate is suggested to provide specific blocking anti-myelin antibodies activity, and thus address MS pathogenesis, which is associated with breach of the immune tolerance to myelin (Morris-Downes et al, 2002 ). Despite the ambiguous data regarding the limited therapeutic efficacy of this drug (Kulakova et al, 2012 ), glatiramer acetate is widely used for MS therapy. It should be noted that these immune modifying drugs are known for particular low efficacy for treatment of primary, and secondary non-remitting (progressive) forms of MS which are less prevalent than relapsing-remitting form of MS but often associated with more severe clinical symptoms (Gajofatto et al, 2016 ).…”