(1) Background: interleukin 23 (IL-23) and interleukin 27 (IL-27) modulate the activity of T helper 17 cells (Th17) with critical roles in autoimmune diseases and multiple sclerosis (MS). The genes responsible for cytokine generation are highly influenced by the presence of single nucleotide polymorphisms (SNP) in main regions such as regulatory sequences or in promoter regions, contributing to disease susceptibility and evolution. The present study analyzed the associations of IL-23 and IL-27 SNPs with susceptibility to multiple sclerosis. (2) Methods: We performed a case-control study including 252 subjects: 157 patients diagnosed with MS and 95 controls. We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to determine the genotypes for IL-27 T4730С (rs 181206), IL-27 A964G (rs 153109), and IL-23 receptor gene (IL-23R) G1142A (rs 11209026). (3) Results: The IL27-T4730С gene polymorphism was significantly associated with an increased odds of MS under the dominant genetic model (TC + CC variant genotypes, adjusted odds ratio OR = 4.06, 95% CI: 2.14–7.83, p-value = 0.000007, Q-value = 0.000063). Individuals carrying the IL-27 A924G variant (AG + GG) genotype presented higher odds of MS compared to non-carriers under the dominant model (adjusted OR = 1.93, 95% CI: 1.05–3.51, p-value = 0.0324, Q-value = 0.05832) and the allelic genetic model (unadjusted p-value = 0.015, OR = 1.58, 95% CI: 1.09–2.28), while IL-23-R381Q SNP conferred a decreased odds of MS under a codominant model of inheritance (adjusted OR = 0.26, 95% CI: 0.08–0.92, p-value = 0.0276, Q-value = 0.058) and an allelic model (unadjusted p-value = 0.008, OR = 0.23, 95% CI: 0.07–0.75). In an additive model with adjustment for age group (≤40 years vs. >40 years), sex and smoking, patients carrying the G-C (A964G, T4730C) haplotype had a 3.18 increased risk (95% CI: 1.74–5.81, p < 0.001) to develop multiple sclerosis. (4) Conclusions: The results of the current study showed a significant relationship of IL-27-A964G and IL-27-T4730C polymorphisms with increased risk of MS, and also the protective role of the IL-23-R381Q polymorphism. Moreover, the haplotype-based analysis proposed the mutant G-C (A924G, T4730C) as a significant risk haplotype for the development of MS.
Background: Multiple sclerosis (MS) is one of the most debilitating neurological diseases of young adults. The presence of a single nucleotide polymorphism in the promoter regions of the interleukin 27 gene (IL27 T4730C, rs181206) may alter the transcription and the production of cytokine levels, leading to MS. Patients and Methods: We performed a case-control study including 82 individuals: 51 patients diagnosed with MS and 31 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism was used in order to determine the genotypes for the IL27 T4730С polymorphism and enzyme-linked immunosorbent assay to measure the serum IL27 level. Results: Carriers of the T4730С polymorphism were found to have a 6-fold [95% confidence intervaI (CI)=1.83-19.63, p=0.002] increased risk for MS. Univariate logistic regression analysis showed an increased frequency of the TC4730 heterozygous genotype (39.2% vs. 9.7%) and also of the C4730 allele (27.45% vs. 8.06) in patients compared to controls, with a 6.02-fold increased risk (95% CI=1.61-22.46, p=0.006) and a 4.31-fold increased risk (95% CI=1.57-11.87, p=0.002) of developing MS. IL27 levels were significantly lower in patients compared to controls (12.35 versus 14.34 pg/ml, p=0.039), without significant differences between genotypes. Multivariate logistic analysis showed that IL27 T4730C polymorphism (odds ratio=6.272, 95% CI=1.84-21.40, p=0.003) and smoking (odds ratio=4.214, 95% CI=1.39-12.74, p=0.011) represented independent risk factors for MS. Conclusion: Our study provides a possible link between IL27 level and IL27 T4730C gene polymorphism and the risk for developing MS in a Romanian population.Multiple sclerosis (MS) is a central nervous system autoimmune disease, characterized by chronic inflammation, myelin damage, oligodendrocyte death and axonal loss leading to neurodegeneration and neurological dysfunctions (1). The pathogenesis of MS is linked to the activation of Tlymphocytes, influenced by environmental and gene interactions (2). In MS, the genetic influence has been demonstrated by genome-wide association studies and familial studies, discovering more than 50 susceptibility loci that contribute to disease onset, such as the polymorphisms located on chromosome 6p21, expressing the human leukocyte antigen class II region of the major histocompatibility complex (MHC), and in other non-MHC loci located near or inside genes controlling the function of the adaptive immune system (3). The involvement of MHC polymorphisms in autoimmune diseases is still unclear but some studies suggested that the binding between T-cell recognition sites and the peptide cleft of MHC molecules might be one explanation, associated with a reduced population of T-regulatory cells and cross reactivity between infectious antigens and self-proteins (4-6). In this respect, 2845This article is freely accessible online.
Multiple sclerosis is one of the main causes of neurological disability among young people, severely influencing life’s quality. Motor deficit is one of the most invalidating symptoms in multiple sclerosis. Motor involvement at onset, spinal demyelinating lesion distribution, highly active lesions, high frequency of relapses in the first 2 years after disease onset and post relapse residual disability with poor recovery, later age at onset and male gender represent unfavorable prognostic factors. Considering the significant role of prognostic factors in predicting the evolution of the disease, an induction treatment approach should always be considered. In this report we present the case of a middle-aged male patient presenting severe weakness and sensitive symptoms with a challenging therapeutic decision that had a favorable recovery after reconsidering the initial therapy. The recognition of aggressive forms of multiple sclerosis is mandatory in preventing further disability, improving the patient’s quality of life. Natalizumab is a monoclonal antibody used for the aggressive forms of multiple sclerosis, reducing the lymphocytes traffic through the blood brain barrier, with a great impact on relapses frequency and disease evolution. Keywords: aggressive multiple sclerosis, brain derived neurotrophic factor, natalizumab, rehabilitation,
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