Stepwise conditional analysis identified HLA-DRB1*04:05, HLA-B*39:01, and HLA-B*15:01 as being associated with independent MS susceptibility (P<sub>Conditional</sub> < 8.3 × 10<sup>-4</sup>).
The MS risk increase in ANO2-seropositive individuals was dramatic when also exposed to 3 known risk factors for MS: <i>HLA-DRB1*15:01</i> carriage, absence of <i>HLA-A*02:01</i>, and high anti-EBNA1 antibody levels (OR = 24.9; 95%CI: 17.9 to 34.8).
Our study confirmed that specific, disease-associated human metabolites bind effectively with the most polymorphic P4 pocket of DRB1*15:01, the primary MS susceptible allele in most populations.
Using flow cytometry we measured surface expression of CD40 and CD86 in B cells from 68 patients and 162 healthy controls that were genotyped for the multiple sclerosis associated single nucleotide polymorphisms (SNPs) rs4810485, which maps within the CD40 gene, and rs9282641, which maps within the CD86 gene.
TLR4 and CD40 co-stimulation synergistically increased the frequency of IL-10-producing but not pro-inflammatory cytokine-producing B cells at MS relapse.
In general, results from the current study indicate that CD226 and HLA-G, but not CD58 genetic polymorphisms are associated with increased risk of MS in Isfahan population similar to European populations.
In conclusion, our results provide support for a sex- and HLA-DRB1*15:01-independent association of TNFRSF1Ars1800693 SNP with MS susceptibility, but not with age at disease onset, severity or rate of disability accumulation.
Stratification of patients with presence of oligoclonal bands (OCB) showed an association to the HLA-DQB1*06:02-HLA-DRB1*15:01 haplotype in ION (HLA-DQB1*06:02 and HLA-DRB1*15:01 (p = 0.03)), and in MS-ON patients (HLA-DQB1*06:02 and HLA-DRB1*15:01 (p = 0.03)).
One major cytokine has been shown to play a pivotal role in several autoimmune diseases such as rheumatoid arthritis (RA) and multiple sclerosis (MS): tumor necrosis factor alpha (TNFα) modulates the induction and maintenance of an inflammatory process and it comes in two variants, soluble TNF (solTNF) and transmembrane bound TNF (tmTNF). tmTNF signals <i>via</i> TNFR1 and TNFR2, whereas solTNF signals mainly <i>via</i> TNFR1.
MS patients with hyperhomocysteinemia showed higher disease progression evaluated by the Multiple Sclerosis Severity Score (MSSS, p < 0.001), disability evaluated by Expanded Disability Status Score EDSS (p < 0.001), TNFR1 (p = 0.039) and ICAM (p = 0.034) than MS patients with lower levels of homocysteine.
Among both ever and never smokers, an interaction between organic solvents, carriage of HLA-DRB1*15, and absence of HLA-A*02 was observed with regard to MS risk, similar to the previously reported gene-environment interaction involving the same MS risk HLA genes and smoke exposure.
The gene polymorphisms at the loci of IL2RArs2104286 and rs12722489 may increase the onset risk of MS. IL2RA-rs2104286 showed a positive relationship with CXCR5-rs3922.
In conclusion, our results provide support for a sex- and HLA-DRB1*15:01-independent association of TNFRSF1A rs1800693 SNP with MS susceptibility, but not with age at disease onset, severity or rate of disability accumulation.