Monocyte and Lymphocyte Activation and Regulation in Multiple Sclerosis Patients. Therapy Effects

Márquez-Coello, Mercedes; Girón-Ortega, José Antonio; Argente, J; Moya, Miguel; Girón-González, José A.

doi:10.1007/s11481-018-09832-z

Cited by 12 publications

(12 citation statements)

References 33 publications

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Section: Discussionmentioning

confidence: 96%

“…Few studies address I-FABP in the setting of MS. Some data indicated that I-FABP as well as ileal bile acid binding protein (IBABP) are increased in MS patients, (67,68), whereas other data did not observe any differences between patients and controls (69). Results herein lend support to the idea that intestinal damages, as indicated by alterations of LPS and I-FABP, are indeed present in MS; further analyses will be needed to sort out these discrepancies The observed alteration of the SCFA/MCFA ratio could thus support MS-associated inflammation with at least two distinct mechanisms: a direct one, which is secondary to the skewing of T lymphocyte functional subset differentiation toward those subsets that support inflammation, and an indirect one driven by alterations in GI tract integrity and microbial translocation.…”

Section: Discussionmentioning

confidence: 96%

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Alterations in Circulating Fatty Acid Are Associated With Gut Microbiota Dysbiosis and Inflammation in Multiple Sclerosis

et al. 2020

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Background: Butyric acid (BA) is a short-chain fatty acid (SCFA) with anti-inflammatory properties, which promotes intestinal barrier function. Medium-chain fatty acids (MCFA), including caproic acid (CA), promote TH1 and TH17 differentiation, thus supporting inflammation. Aim: Since most SCFAs are absorbed in the cecum and colon, the measurement of BA in peripheral blood could provide information on the health status of the intestinal ecosystem. Additionally, given the different immunomodulatory properties of BA and CA the evaluation of their serum concentration, as well as their ratio could be as a simple and rapid biomarker of disease activity and/or treatment efficacy in MS. Methods: We evaluated serum BA and CA concentrations, immune parameters, intestinal barrier integrity and the gut microbiota composition in patients with multiple sclerosis (MS) comparing result to those obtained in healthy controls. Results: In MS, the concentration of BA was reduced and that of CA was increased. Concurrently, the microbiota was depleted of BA producers while it was enriched in mucin-degrading, pro-inflammatory components. The reduced serum concentration of BA seen in MS patients correlated with alterations of the barrier permeability, as evidenced by the higher plasma concentrations of lipopolysaccharide and intestinal fatty acid-binding protein, and inflammation. Specifically, CA was positively associated with CD4+/IFNγ+ T lymphocytes, and the BA/CA ratio correlated positively with CD4+/CD25 high /Foxp3+ and negatively with CD4+/IFNγ+ T lymphocytes. Conclusion: The gut microbiota dysbiosis found in MS is possibly associated with alterations of the SCFA/MCFA ratio and of the intestinal barrier; this could explain the chronic inflammation that characterizes this disease. SCFA and MCFA quantification could be a simple biomarker to evaluate the efficacy of therapeutic and rehabilitation procedures in MS.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 96%

Alterations in Circulating Fatty Acid Are Associated With Gut Microbiota Dysbiosis and Inflammation in Multiple Sclerosis

et al. 2020

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“…Studies on IPC in MS and EAE are not very numerous. Approximately 20 years ago, studying co-morbidity between Crohn's disease and MS, a first finding of increased IP was reported in a minority of cases with MS (13). The recent momentum of the gut-brain axis role in the pathogenesis of neuroinflammation prompted studies on IP changes in EAE.…”

Section: Introductionmentioning

confidence: 99%

The Contribution of Gut Barrier Changes to Multiple Sclerosis Pathophysiology

et al. 2019

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The gut barrier consists of several components, including the mucus layer, made of mucins and anti-bacterial molecule, the epithelial cells, connected by tight junction proteins, and a mixed population of cells involved in the interplay with microbes, such as M cells, elongations of “antigen presenting cells” dwelling the lamina propria, intraepithelial lymphocytes and Paneth cells secreting anti-bacterial peptides. Recently, the influence of intestinal permeability (IP) changes on organs far from gut has been investigated, and IP changes in multiple sclerosis (MS) have been described. A related topic is the microbiota dysfunction that underpins the development of neuroinflammation in animal models and human diseases, including MS. It becomes now of interest to better understand the mechanisms through which IP changes contribute to pathophysiology of neuroinflammation. The following aspects seem of relevance: studies on other biomarkers of IP alterations; the relationship with known risk factors for MS development, such as vitamin D deficiency; the link between blood brain barrier and gut barrier breakdown; the effects of IP increase on microbial translocation and microglial activation; the parallel patterns of IP and neuroimmune changes in MS and neuropsychiatric disorders, that afflict a sizable proportion of patients with MS. We will also discuss the therapeutic implications of IP changes, considering the impact of MS-modifying therapies on gut barrier, as well as potential approaches to enhance or protect IP homeostasis.

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“…Several studies in MS and in its animal model, experimental autoimmune encephalomyelitis, suggest that GA treatment is associated with an immunomodulatory effect acting broadly on cells of both the innate and adaptive immune system. For instance, GA therapy reduces the fraction of activated CD8 + T cells, 22 remodels the composition of the B- and T-cell compartment, and influences cytokine secretion and immunoglobulin production following modulation of antigen-presenting cells' functions. 23 – 25 Our data show that after treatment, there are clear changes within the B-cell subset: naive B cells increase as opposed to memory B cells, and this occurrence is preceded by the expression on the FAS receptor on memory B cells.…”

Section: Discussionmentioning

confidence: 99%

EBV-specific CD8 T lymphocytes and B cells during glatiramer acetate therapy in patients with MS

Guerrera

Ruggieri

Picozza

et al. 2020

Neurol Neuroimmunol Neuroinflamm

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ObjectiveInfection with Epstein-Barr virus (EBV) has been associated with clinical activity and risk of developing MS. The purpose of this study is to investigate the impact of glatiramer acetate (GA) therapy on EBV-specific immune responses and disease course.MethodsWe characterized EBV-specific CD8 T lymphocytes and B cells during disease-modifying treatments in 2 groups of patients with MS. We designed a 2-pronged approach consisting of a cross-sectional study (39 untreated patients, 38 patients who had undergone 12 months of GA treatment, and 48 healthy donors compatible for age and sex with the patients with MS) and a 12-month longitudinal study (35 patients treated with GA). CD8 EBV-specific T cells and B lymphocytes were studied using pentamers and multiparametric flow cytometry.ResultsWe find that treatment with GA enhances viral recognition by inducing an increased number of circulating virus-specific CD8 T cells (p = 0.0043) and by relieving their features of exhaustion (p = 0.0053) and senescence (p < 0.0001, p = 0.0001). B cells, phenotypically and numerically tracked along the 1-year follow-up study, show a steady decrease in memory B-cell frequencies (p = 0.025), paralleled by an increase of the naive B subset.ConclusionGA therapy acts as a disease-modifying therapy restoring homeostasis in the immune system, including anti-EBV responses.

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Monocyte and Lymphocyte Activation and Regulation in Multiple Sclerosis Patients. Therapy Effects

Cited by 12 publications

References 33 publications

Alterations in Circulating Fatty Acid Are Associated With Gut Microbiota Dysbiosis and Inflammation in Multiple Sclerosis

Alterations in Circulating Fatty Acid Are Associated With Gut Microbiota Dysbiosis and Inflammation in Multiple Sclerosis

The Contribution of Gut Barrier Changes to Multiple Sclerosis Pathophysiology

EBV-specific CD8 T lymphocytes and B cells during glatiramer acetate therapy in patients with MS

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