Multiple Sclerosis: Immunopathology and Treatment Update

Dargahi, Narges; Katsara, Maria; Tselios, Theodore; Androutsou, Maria Eleni; Courten, Maximilian de; Matsoukas, John; Apostolopoulos, Vasso

doi:10.3390/brainsci7070078

Cited by 224 publications

(194 citation statements)

References 183 publications

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“…Various studies have illustrated the role of TGF-β1 in inciting the production of IL-10 [32,37,38], and also, it has become elucidated that TGF-β1 can trigger IL-10 through Smad4 pathway [16]. Following the same issue, TGF-β1 could repress the differentiation of naive CD4+ T cells into pathogenic Th17 ones and down-regulate the mRNA expression of IL-17 due to the immunosuppressive traits [39][40][41]. However, there are contradictory results about the impact of TGF-β1 on the differentiation of Th17 to IL-17 in a way that some of them indicated that TGF-β1 was able to trigger the differentiation of Th17 to IL-17 [42,43].…”

Section: Plos Onementioning

confidence: 99%

The impact of vitamin D3 intake on inflammatory markers in multiple sclerosis patients and their first-degree relatives

et al. 2020

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Background & aimsIn our previous study, a Seesaw model was proposed for the fluctuation of crucial anti-(IL-10) and pro-inflammatory (Il-6 & IL-17A) cytokines through vitamin D 3 . In this paper, however, it is intended to extend the mentioned model by assessing the expression mRNA levels of IL-27 and TGF-β1 as well as the changes of plasma levels of IL-27, TGF-β1, IL-17A, IL-10, and IL-6 after treatment by vitamin D 3 . MethodVenous blood samples were drawn from Healthy Participants (HP, n = 25) and First-Degree Relative Participants (FDRP, n = 25) as control groups and Multiple Sclerosis Participants (MSP, n = 25) before and after eight weeks of supplementation with 50000 IU vitamin D 3 . The mRNA expression and plasma concentrations were gauged by using Real-Time PCR and ELISA assay, respectively.

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Section: Plos Onementioning

confidence: 99%

The impact of vitamin D3 intake on inflammatory markers in multiple sclerosis patients and their first-degree relatives

et al. 2020

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“…Interferon beta formulations were the first DMTs approved for the treatment of RMS (Dargahi et al, 2017). Peginterferon beta-1a was developed by covalently attaching a polyethylene glycol side chain to interferon beta-1a (Kieseier and Calabresi, 2012).…”

Section: Introductionmentioning

confidence: 99%

Matching-adjusted comparisons demonstrate better clinical outcomes in patients with relapsing multiple sclerosis treated with peginterferon beta-1a than with teriflunomide

Newsome

Mokliatchouk

Castrillo‐Viguera

et al. 2020

Multiple Sclerosis and Related Disorders

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Background: Peginterferon beta-1a and teriflunomide are both first-line disease-modifying therapies (DMTs) approved for the treatment of relapsing multiple sclerosis (RMS); however, no head-to-head trials have directly compared their clinical efficacy. We performed a matching-adjusted comparison of individual patient data from the peginterferon beta-1a pivotal phase 3 study, ADVANCE, and its extension study, ATTAIN, with pooled aggregated data from the teriflunomide pivotal phase 3 studies, TEMSO and TOWER. Methods: A total of 512 patients randomized to subcutaneous (SC) peginterferon beta-1a 125 mcg every 2 weeks in ADVANCE and 731 patients randomized to teriflunomide 14 mg daily (359 from TEMSO and 372 from TOWER) were matched on key baseline characteristics. After matching, weighted annualized relapse rate (ARR) and 24-week confirmed disability worsening (CDW) were calculated and compared for peginterferon beta-1aand teriflunomide-treated patients. A subset analysis comparing weighted ARR in patients who were newly diagnosed with RMS (diagnosis ≤1 year before study enrollment and disease-modifying therapy naïve) was also performed. Results: After matching, the peginterferon beta-1a and teriflunomide treatment groups were identically matched across baseline characteristics. The proportion of patients in the overall study populations with 24-week CDW at 108 weeks was significantly lower in the peginterferon beta-1a group than the teriflunomide group both before matching (8.5% vs 12.6%; P = 0.0249) and after matching (8.4% vs 12.6%; P = 0.0323). ARR at 108 weeks was numerically lower with peginterferon beta-1a than with teriflunomide both before matching (0.278 vs 0.354; P = 0.1326) and after matching (0.257 vs 0.354; P = 0.0510). Newly diagnosed patients treated with peginterferon beta-1a had numerically lower ARR than patients treated with teriflunomide both at 108 weeks (before matching: 0.225 vs 0.270; P = 0.587; after matching: 0.201 vs 0.270; P = 0.384) and at 5 years (before matching: 0.150 vs 0.196; after matching: 0.142 vs 0.196). Conclusions: In this matching-adjusted comparison of patients with RMS from three phase 3 trials, a significantly lower proportion of patients treated with SC peginterferon beta-1a 125 mcg every 2 weeks than with oral teriflunomide 14 mg once daily had 24-week CDW at 108 weeks. In addition, in both the overall population and newly diagnosed patient subgroups, ARR at 108 weeks was numerically lower with peginterferon beta-1a than with teriflunomide. The numerically lower ARR in newly diagnosed patients treated with peginterferon beta-1a compared with those treated with teriflunomide was sustained through up to 5 years of treatment.

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“…However, 50–70% of RRMS patients become chronic and develop secondary progressive MS (SPMS), which is characterized by continuous progression (Rovaris et al, ). Although previous studies identified the pathological mechanism of RRMS and developed treatments to prevent relapsing (Dargahi et al, ), the pathological mechanism of SPMS remains poorly understood. Therefore, it is necessary to elucidate the pathological molecular mechanism associated with SPMS in order to develop a therapeutic strategy.…”

Section: Introductionmentioning

confidence: 99%

Microglia suppress the secondary progression of autoimmune encephalomyelitis

Tanabe

Saitoh

Miyajima

et al. 2019

Glia

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Secondary progressive multiple sclerosis (SPMS) is an autoimmune disease of the central nervous system (CNS) characterized by progressive motor dysfunction, sensory deficits, and visual problems. The pathological mechanism of SPMS remains poorly understood. In this study, we investigated the role of microglia, immune cells in the CNS, in a secondary progressive form of experimental autoimmune encephalomyelitis (EAE), the mouse model of SPMS. We induced EAE in nonobese diabetic mice and treated the EAE mice with PLX3397, an antagonist of colony stimulating factor‐1 receptor, during secondary progression in order to deplete microglia. The results showed that PLX3397 treatment significantly exacerbated secondary progression of EAE and increased mortality rates. Additionally, histological analysis showed that PLX3397 treatment significantly promoted inflammation, demyelination, and axonal degeneration. Moreover, the number of CD4+ T cells in the spinal cord of EAE mice was expanded due to PLX3397‐mediated proliferation. These results suggest that microglia suppressed secondary progression of EAE by inhibiting the proliferation of CD4+ T cells in the CNS.

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Multiple Sclerosis: Immunopathology and Treatment Update

Cited by 224 publications

References 183 publications

The impact of vitamin D3 intake on inflammatory markers in multiple sclerosis patients and their first-degree relatives

The impact of vitamin D3 intake on inflammatory markers in multiple sclerosis patients and their first-degree relatives

Matching-adjusted comparisons demonstrate better clinical outcomes in patients with relapsing multiple sclerosis treated with peginterferon beta-1a than with teriflunomide

Microglia suppress the secondary progression of autoimmune encephalomyelitis

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