γ-H2AX and 53BP1 foci do not seem to be promising diagnostic or disease activity biomarkers in patients with early MS. Lymphocytic DNA double-strand breaks are unlikely to play a major role in the pathophysiology of MS.
γ-H2AX expression in peripheral blood mononuclear cells (PBMCs) was recently proposed as a diagnostic and disease activity marker for multiple sclerosis (MS).
[Alpha]B-crystallin is a candidate autoantigen in MS, and there are three polymorphisms in the promoter region of the encoding gene (CRYAB): at positions -C249G, -C650G, and -A652G.
Zeste homolog 2 (EZH2) has sparked extensive interest because of its pleiotropic roles in distinct pathologic contexts.<b>Areas covered</b>: This review summarizes the epigenetic functions and the biological significance of EZH2 in the etiology of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), inflammatory bowel disease (IBD), multiple sclerosis (MS), and systemic sclerosis (SSc).
Women with relapsing-remitting (RR) MS were randomly assigned (1:1:1) to receive subcutaneous IFN-β-1a (Rebif<sup>®</sup>, Merck Serono, Geneva, Switzerland) 44 mcg three times a week (tiw) (group 1), subcutaneous IFN-β-1a 44 mcg tiw plus ethinyl estradiol 20 mcg and desogestrel 150 mcg (Mercilon<sup>®</sup>, MSD Italia SRL, Rome, Italy) (group 2) or subcutaneous IFN-β-1a 44 mcg tiw plus ethinyl estradiol 40 mcg and desogestrel 125 mcg (Gracial<sup>®</sup>, Organon Italia S.p.A., Rome, Italy) (group 3) in a randomised controlled trial, for which we report the analysis of secondary outcomes.
Within these protective haplotypes in DR2-negative individuals, both DQA1 alleles and one DQB1 allele (*0604) were protective, but neither DR allele was protective, i.e., DQ loci may be more important than DR loci in encoding molecules protective against MS. Predispositional (Phe67) and protective (Ile67) DR beta sequence motifs were present in the total and DR2-negative patient and control groups.
Within the MPHOSPH9/CDK2AP1 locus, the risk allele correlates with diminished RNA expression of the cell cycle regulator CDK2AP1; this effect is seen in both lymphoblastic cell lines (P=1.18 x 10(-5)) and in peripheral blood mononuclear cells from subjects with MS (P=0.01).
Within the MPHOSPH9/CDK2AP1 locus, the risk allele correlates with diminished RNA expression of the cell cycle regulator CDK2AP1; this effect is seen in both lymphoblastic cell lines (P=1.18 x 10(-5)) and in peripheral blood mononuclear cells from subjects with MS (P=0.01).
Within the 1051 highly variable genes that differentiated between multiple sclerosis-to-be and multiple sclerosis-free subjects, we identified activation of TCR signaling that triggered the Cbl and MAPK cascade in concert with downstream synergic over-expression of NFAT and MEF2B, but failed to augment the expression of the nuclear receptor gene family members NR4A1, NR2F1, VDR and MEF2B, that further resulted in impaired apoptotic machinery.
Within and around active MS plaques lacking remyelination, Jagged1 was expressed at high levels by hypertrophic astrocytes, whereas Notch1 and Hes5 localized to cells with an immature oligodendrocyte phenotype, and TGF-beta 1 was associated with perivascular extracellular matrix in the same areas.
With this aim, we evaluated the influence of the TCRBV20S1 polymorphism by assessing it with the transmission disequilibirum test (TDT) in 652 T1D and 616 MS families, without detecting any significant difference.
With the discovery of the disease-specific aquaporin-4 antibody and the increasing recognition of clinical and characteristic imaging patterns of brain involvement in what is now termed neuromyelitis optica spectrum disorder (NMOSD), MRI now plays a greater role in diagnosis of NMOSD based on the 2015 consensus criteria and in distinguishing it from other inflammatory disorders, particularly multiple sclerosis (MS).
With respect to MS, IL-1 beta (-511 C/T; rs16944), IL-1 beta (+3954 C/T; rs1143634), IL-1 alpha (-889 C/T; rs1800587), IL-1 alpha (+4845 G/T; rs17561), and the variable number of tandem repeats in intron 2 of the IL-1 receptor antagonist (IL-1RN) gene polymorphisms have been studied in different ethnic groups, leading to conflicting results.
With regard to T cells of MS patients: (1) The cell surface expression of a specific GluR: the AMPA GluR3 is elevated in T cells of MS patients during relapse and with active disease, (2) Glutamate and AMPA (a selective agonist for glutamate/AMPA iGluRs) augment chemotactic migration of T cells of MS patients, (3) Glutamate augments proliferation of T cells of MS patients in response to myelin-derived proteins: MBP and MOG, (4) T cells of MS patients respond abnormally to glutamate, (5) Significantly higher proliferation values in response to glutamate were found in MS patients assessed during relapse, and in those with gadolinium (Gd)+ enhancing lesions on MRI.
With regard to T cells of MS patients: (1) The cell surface expression of a specific GluR: the AMPA GluR3 is elevated in T cells of MS patients during relapse and with active disease, (2) Glutamate and AMPA (a selective agonist for glutamate/AMPA iGluRs) augment chemotactic migration of T cells of MS patients, (3) Glutamate augments proliferation of T cells of MS patients in response to myelin-derived proteins: MBP and MOG, (4) T cells of MS patients respond abnormally to glutamate, (5) Significantly higher proliferation values in response to glutamate were found in MS patients assessed during relapse, and in those with gadolinium (Gd)+ enhancing lesions on MRI.
With a view to an association of HLA class II genes, specifically HLA-DRB1 subtype DRB1*15 to multiple sclerosis we investigated the HLA class II DR haplotype in 29 unrelated X-ALD patients including 17 childhood cerebral phenotype patients.
With a view to an association of HLA class II genes, specifically HLA-DRB1 subtype DRB1*15 to multiple sclerosis we investigated the HLA class II DR haplotype in 29 unrelated X-ALD patients including 17 childhood cerebral phenotype patients.
While we identified new single nucleotide polymorphism (SNP) and confirmed previously reported SNPs, none of the SNPs was associated with MS. Our findings demonstrate that sCD21 expression is altered in MS patients similar to other autoimmune diseases although no evidence was found for a specific role of the CD21 gene in MS.
While this phenomenon has been well described for multiple sclerosis (MS) patients, it never has been tested on asymptomatic subject with magnetic resonance imaging (MRI) findings suggestive of demyelinating disease (i.e., radiologically isolated syndrome: RIS).
While part of the association of the apoE polymorphism with AD is supposed to be caused by apoE-isoform dependent effects on amyloid-beta deposition, no single pathogenetically relevant mechanism has yet been confirmed for MS.
While no clones that shared the same CDR3 amino acid sequences were seen in either HC or MS patients, there was a cluster of related CDR3 amino acid sequences observed for 18 out of 34 MS patients when evaluated by phylogenetic tree analysis.