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Exosomes are a nano-vesicle surrounded by a bilipid layer that can release from almost all cells and could be detected in tissues and biological liquids. These vesicles contain lipids, proteins, and nucleic acids (including DNA, mRNA, and miRNA) inside and on the exosomes' surface constitute their content. Exosomes can transfer their cargo into the recipient cell, which can modify recipient cells' biological activities. Recently it has been deciphering that the miRNA pattern of exosomes reveals the cellular pathophysiological situation and modifies various biological processes. Increasing data regarding exosomes highlights that the exosomes and their cargo, especially miRNAs, are implicated in the pathophysiology of various disorders, such as autoimmune disease. The current evidence on the deciphering of mechanisms in which exosomal miRNAs contributed to autoimmunity was indicated that exosomal miRNA might hold information that can reprogram the function of many of the immune cells involved in autoimmune diseases' pathogenesis. In the present study, we summarized the pathogenic role of exosomal miRNAs in several autoimmune diseases, including myasthenia gravis (MG), psoriasis, inflammatory bowel disease (IBD), type 1 diabetes (T1D), multiple sclerosis (MS), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjogren's Syndrome (SS), systemic sclerosis (SSc), vitiligo, and autoimmune thyroid diseases (AITD). Moreover, in this work, we present evidence of the potential role of exosomal miRNAs as therapeutic and diagnostic agents in autoimmune diseases., (Copyright © 2021. Published by Elsevier B.V.)

Multiple sclerosis (MS) is a destructive autoimmune neuroinflammatory and neurodegenerative disorder of the central nervous system (CNS) with unknown etiology and mechanism of pathogenesis. Pathogens, especially human herpes viruses, have been suggested as environmental factors of the MS and other neuroinflammatory disorders. This study aimed to determine the prevalence of HHV-6 antibody response in MS patients and investigate the levels of pro/anti-inflammatory cytokine and chemokines in MS patients in comparison with healthy subjects. Two hundred sixty-three patients with clinically defined MS (140 females and 123 males), along with 263 healthy subjects (140 females and 123 males), were recruited for this study. After the analysis of HHV-6 seropositivity/seronegativity, the levels of some pro/anti-inflammatory cytokines, including TNF-α, IFN-γ, IL-1β, IL-6, and IL-12 as well as two chemokines, namely CCL-2 and CCL-5 were determined by the enzyme-linked immunosorbent assay (ELISA) method in HHV-6 seropositive/seronegative MS patients and healthy subjects. Our results showed that the serum concentrations of TNF-α, IFN-γ, IL-1β, IL-6, and CCL-5 elevated in HHV-6 seropositive compared with seronegative MS patients (P < .05). Moreover, the levels of IL-12, IL-10, and CCL-2 levels were significantly lower in seropositive MS patients when compared with seronegative MS patients (P < .05). Also, our results revealed that the mean values of the expanded disability status scale (EDSS) were significantly higher in HHV-6 seropositive versus seronegative MS patients (P < .05). In conclusion, we proposed that HHV-6 infection may play a role in MS pathogenesis by changing cytokine signaling in MS patients that may lead to peripheral inflammation., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In recent years, a possible protective role of Helicobacter pylori (Hp) against autoimmune disease has been reported in an experimental murine model of multiple sclerosis (MS), and there are restricted conflicting epidemiologic data concerning Hp serology in MS patients. This study was aimed to determine the seroprevalence of Hp in MS patients and then investigates pro/anti-inflammatory cytokine levels in MS patients infected with HP and seronegative MS patients. Three hundred eighty-seven patients with MS were included in the study and were adjusted by gender and age to 420 healthy subjects. An enzyme-linked immunoassay (ELISA) was used to determine the presence of specific IgG antibodies against H. pylori in the serum sample of both groups. Some pro/anti-inflammatory cytokines levels were evaluated in seropositive/seronegative MS patients and healthy individuals. Our result showed that in patients with MS HP seropositivity was significantly lower than the healthy individual (P < .0001). Also, we showed that HP seropositive MS patients had lower Expanded Disability Status Scale (EDSS) when compared with seronegative MS patients (P < .011). Moreover, we illustrated that proinflammatory cytokine levels include IFN-γ, TNF-α, IL-6, and IL-17 in MS patients infected with HP were lower than seronegative MS patients. Besides, the levels of anti-inflammatory cytokines include IL-4 and IL-10 was significantly higher in MS patients infected with HP when compared with MS patients seronegative for HP infection. In this study, we indicated that HP infection negatively correlated with MS, and conceivably may act as a protective agent against MS. The precise mechanism behind this protective effect remains elusive. However, it seems HP can modulate cytokine signaling, which involved in MS pathogenesis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Multiple Sclerosis (MS) is thought to be an autoimmune disease of the central nervous system (CNS), in which the immune system becomes activated, cross the blood-brain barrier (BBB), and cause neuroinflammation and neurodegeneration. Fingolimod is considered a disease-modifying therapy (DMT), possessing immunomodulatory effects on the immune system, especially autoreactive T cells being licensed in lymph nodes. Although the fidelity of the drug is undeniable in the management of disease course, various adverse effects have been reported in some patients taking this medication. In this study, 420 MS patients, consisted of 210 patients receiving interferon-beta (IFN-beta) and 210 patients receiving fingolimod therapies. As a control group, 210 age- and sex-matched healthy individuals were recruited in our study. The levels of anti-VZV IgG and IgM were determined using enzyme-linked immunosorbent assay (ELISA). The presence of VZV DNA in peripheral blood mononuclear cells (PBMCs) was also investigated using the PCR method. The percentage of seropositivity for anti-VZV IgG and anti-VZV IgM in MS patients was 94.8% and 0%, respectively in those taking fingolimod therapy. In patients receiving IFN-beta, the rate of seropositivity for anti-VZV IgG and anti-VZV IgM was 93.8% and 0%, respectively. In healthy individuals, the rate of seropositivity for anti-VZV IgG and anti-VZV IgM was 84.3% and 0%, respectively. The PCR results showed that 7.6% of patients receiving fingolimod were positive for VZV DNA, while none of the healthy subjects nor MS patients taking IFN-beta were positive for DNA of VZV. The statistical analysis indicated that the frequency of VZV DNA in patients receiving fingolimod was significantly (p = .00) higher than MS patients taking IFN-beta and healthy subjects. It seems that the use of fingolimod should be carefully prescribed as the occurrence of VZV infection/reactivation is increased in comparison to other MS patients who receive different therapy., (Copyright © 2018. Published by Elsevier B.V.)

Multiple Sclerosis (MS) is a neuroinflammatory disease of the central nervous system (CNS) in which immune system plays a crucial role in progression of the disease. An enormous amount of research has been shown that immune mediators such as cytokines and chemokines are the culprits of MS propagation suggesting that modulation of such molecules may pave the path to hinder the disease development. It has been shown that both CD21 and CD83 contribute to the resolution of inflammation occurred in MS. CD21 and CD83 have also been ascribed to Epstein Barr virus (EBV) infection (the prime suspect of MS causality) and the levels of vitamin D, respectively. Hence, in this study, we measured the serum concentrations of soluble forms of CD21 and CD83 in 255 patients with MS divided into two groups who were receiving interferon-beta (185 MS patients) and fingolimod (70 MS patients) in comparison to 384 healthy individuals. The levels of EBV titers including anti-VCA IgM, anti-VCA IgG and anti-EBNA-1 IgG were also measured. The results showed that the concentration of soluble CD21 (sCD21) was markedly decreased in serum samples of MS patients with respect of controls. Contrarily, the level of soluble CD83 (sCD83) was elevated in MS patients compared to healthy individuals. In addition, the levels of sCD21 and sCD83 were correlated with the titers of EBV. The data showed the significant association between the expanded disability status scale (EDSS) and the levels of both sCD21 and sCD83. It seems that both sCD21 and sCD83 might be good candidate for disease monitoring and can be considered potential biomarkers for the disease activity., (Copyright © 2018. Published by Elsevier B.V.)

Multiple Sclerosis is a demyelinating disease of the central nervous system (CNS) affecting young individuals with age range of 20-40years of age. The precise mechanism underlying the disease is still unclear. Some viruses have been proposed to play roles in disease causation. In this study, we recruited 800 MS patients along with 1000 healthy individuals to determine the seropositivity of anti-CMV and anti-VZV IgG titers using enzyme-linked immunosorbent assay (ELISA). Our results showed significant higher titers of anti-CMV and anti-VZV IgG titers in serum of MS patients with respect to healthy individuals (for both p<0.001). It seems that CMV and VZV play a key role in MS pathogenesis., (Copyright © 2017. Published by Elsevier B.V.)

A growing body of evidence suggests that angiogenesis plays a crucial role in the pathogenesis of multiple sclerosis (MS). Animal models of MS show a significant improvement when the process of angiogenesis is halted. In this study, we measured the serum levels of vascular-endothelial growth factor (VEGF), soluble Endoglin (sEng), angiopoietin 1(Ang-1), angiopoietin 2 (Ang-2), and uric acid (UA) as well as serum anti-Epstein-Barr virus (EBV) EBNA-1 IgG in 50 MS patients (including 20 newly diagnosed and 30 patients taking IFN-beta for >6months) and 40 healthy individuals. Enzyme-linked immunosorbent assays (ELISA) were used apart from UA where the uricase quantitative enzymatic assay was used. A significant increase of VEGF, Ang-1, Ang-2, and sEng in serum samples of MS patients with respect to healthy subjects was observed. VEGF was higher in newly diagnosed MS patients in comparison to patients taking interferon-beta and was associated with EDSS. The serum levels of UA were statistically lower in MS patients as compared to the healthy group. Higher levels of anti-EBV antibody titers were seen in MS patients than controls and anti-EBV titers correlated with angiogenic factors. It seems that in summary, angiogenesis may play an important role in MS and infection with EBV might be correlated with this phenomenon., (Copyright © 2016. Published by Elsevier B.V.)

Vitamin D is being increasingly studied in multiple sclerosis (MS). A number of studies have shown that MS patients have lower levels of 25-hydroxyvitamin D as compared to comparator populations, but previous studies in Iran have been conflicting, perhaps due to their small sample size. We performed the largest study to date investigating 25-hydroxyvitamin D levels in Iranian MS patients (n=700) and controls (n=1000). 25-hydroxyvitamin D was measured using a quantitative chemiluminescent immunometric assay. 25-hydroxyvitamin D levels were lower in patients with MS. Over 24% of controls were vitamin D sufficient as compared to 3.4% of patients. Logistic regression showed that for every 1 ng/mL increase in 25-hydroxyvitamin D, the odds for MS decreased (odds ratio=0.87; 95% confidence interval (CI) 0.85-0.88; p<0.001), after adjusting for age and sex. There was no association between 25-hydroxyvitamin D levels and disability scores in MS patients. Iranian Patients with MS have low levels of vitamin D and, where deemed necessary, appropriate supplementation should be given., (Copyright © 2015 Elsevier B.V. All rights reserved.)