The Impact of IgA and the Microbiota on CNS Disease

Pu, Annie; Lee, Dennis S. W.; Isho, Baweleta; Naouar, Ikbel; Gommerman, Jennifer L.

doi:10.3389/fimmu.2021.742173

Cited by 5 publications

(4 citation statements)

References 100 publications

(133 reference statements)

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“…In contrast, decreased BAFF-R expression affected multiple B cell subsets, was persistent over time and not related to reactivation of EBV, possibly indicating that it is an effect of persistently increased BAFF production by pathogenic B cells in the CNS, which are reportedly infected by EBV ( 45 ). Similarly, the increased abundance of circulating IgA + MBCs was not related to reactivation of EBV infection and may provide further evidence of a link between the mucosal immune system of the gut and the immunopathogenesis of MS ( 57 ).…”

Section: Discussionmentioning

confidence: 94%

Circulating Memory B Cells in Early Multiple Sclerosis Exhibit Increased IgA+ Cells, Globally Decreased BAFF-R Expression and an EBV-Related IgM+ Cell Signature

et al. 2022

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Multiple sclerosis (MS) is an immune-mediated inflammatory disease of the central nervous system that results in demyelination of axons, inefficient signal transmission and reduced muscular mobility. Recent findings suggest that B cells play a significant role in disease development and pathology. To further explore this, B cell profiles in peripheral blood from 28 treatment-naive patients with early MS were assessed using flow cytometry and compared to 17 healthy controls. Conventional and algorithm-based analysis revealed a significant increase in MS patients of IgA+ memory B cells (MBC) including CD27+, CD27- and Tbet+ subsets. Screening circulating B cells for markers associated with B cell function revealed a significantly decreased expression of the B cell activation factor receptor (BAFF-R) in MS patients compared to controls. In healthy controls, BAFF-R expression was inversely associated with abundance of differentiated MBC but this was not observed in MS. Instead in MS patients, decreased BAFF-R expression correlated with increased production of proinflammatory TNF following B cell stimulation. Finally, we demonstrated that reactivation of Epstein Barr Virus (EBV) in MS patients was associated with several phenotypic changes amongst MBCs, particularly increased expression of HLA-DR molecules and markers of a T-bet+ differentiation pathway in IgM+ MBCs. Together, these data suggest that the B cell compartment is dysregulated in MS regarding aberrant MBC homeostasis, driven by reduced BAFF-R expression and EBV reactivation. This study adds further insights into the contribution of B cells to the pathological mechanisms of MS, as well as the complex role of BAFF/BAFF-R signalling in MS.

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Section: Discussionmentioning

confidence: 94%

Circulating Memory B Cells in Early Multiple Sclerosis Exhibit Increased IgA+ Cells, Globally Decreased BAFF-R Expression and an EBV-Related IgM+ Cell Signature

et al. 2022

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“…In a well-characterised Italian cohort, the gut microbiome of centenarians had higher abundance of several taxa such as Akkermansia and Christensenellaceae , some of which have previously been associated with health, suggesting they may contribute to the maintenance of health during ageing ( Biagi et al, 2016 ). Meanwhile, other research found that Ruminococcaceae , Lachnospiraceae and Bacteroidaceae families decreased with advancing age ( Biagi et al, 2016 ; Pu et al, 2021 ). In another investigation in South Korea, Akkermansia , Collinsella , Clostridium and Christensenellaceae were increased in the faecal microbiome of centenarians, while there was a decreased abundance of Faecalibacterium and Prevotella ( Kim et al, 2019b ).…”

Section: Biological Ageing Drives Changes To the Gut Microbiomementioning

confidence: 98%

The gut microbiota is an emerging target for improving brain health during ageing

et al. 2022

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The gut microbiota plays crucial roles in maintaining the health and homeostasis of its host throughout lifespan, including through its ability to impact brain function and regulate behaviour during ageing.Studies have shown that there are disparate rates of biologic ageing despite equivalencies in chronologic age, including in the development of neurodegenerative diseases, which suggests that environmental factors may play an important role in determining health outcomes in ageing. Recent evidence demonstrates that the gut microbiota may be a potential novel target to ameliorate symptoms of brain ageing and promote healthy cognition. This review highlights the current knowledge around the relationships between the gut microbiota and host brain ageing, including potential contributions to agerelated neurodegenerative diseases. Furthermore, we assess key areas for which gut microbiota-based strategies may present as opportunities for intervention.

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“…Coating of intestinal commensals by host plasma cell-derived IgA represents a crucial host response for maintaining immune homeostasis in the context of autoimmune neuroinflammation (29)(30)(31). Secretory IgA (sIgA) levels in the mouse feces were disconnected from individual EAE outcomes (Fig.…”

Section: Iga Coating Index Of Bacteroides Ovatus Represents a Surroga...mentioning

confidence: 99%

Gut microbiome-based prediction of autoimmune neuroinflammation

Steimle

Neumann

Grant

et al. 2023

Preprint

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Given the gut microbiota’s contribution to pathogenesis of autoimmune diseases, microbiota characteristics could potentially be used to predict disease susceptibility or progression. Although various gut commensals have been proposed as risk factors for autoimmune disease development, predictions based on microbiota composition alone remain unreliable. Here, we evaluated a common approach to identify a potential microbial risk factor from complex communities, followed by in-depth evaluation of its risk factor properties using an autoimmune neuroinflammation disease model in mice harboring several distinct, defined microbiota compositions. We found that the relative abundances of commensal taxa across distinct communities are poorly suited to assess the disease-mediating property of a given microbiota. Instead, the presence of certain microbial risk factors allowed us to determine the probability of severe disease, but failed to predict the individual disease course. We investigated multiple other microbiota-associated characteristics by applying 16S rRNA gene sequencing, metatranscriptomic and metabolomic approaches, as well as in-depth analysis of host immune responses and intestinal barrier integrity-associated readouts. By leveraging gnotobiotic mouse models harboring six defined compositions, we identified the IgA coating index ofBacteroides ovatusas a reliable individual disease risk predictor before disease onset, due to its ability to reflect autoimmunity-mediating properties of a given gut microbial network within a specific host. In summary, our data suggest that common taxonomic analysis approaches should be refined by taxonomic network analyses or combined with microbiota function-related readouts to reliably assess disease predisposition of a given host−microbiota combination.

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The Impact of IgA and the Microbiota on CNS Disease

Cited by 5 publications

References 100 publications

Circulating Memory B Cells in Early Multiple Sclerosis Exhibit Increased IgA+ Cells, Globally Decreased BAFF-R Expression and an EBV-Related IgM+ Cell Signature

Circulating Memory B Cells in Early Multiple Sclerosis Exhibit Increased IgA+ Cells, Globally Decreased BAFF-R Expression and an EBV-Related IgM+ Cell Signature

The gut microbiota is an emerging target for improving brain health during ageing

Gut microbiome-based prediction of autoimmune neuroinflammation

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