<i>Prevotella copri</i>
in individuals at risk for rheumatoid arthritis

Alpizar-Rodriguez, D.; Lesker, Till Robin; Gronow, Achim; Gilbert, Benoît; Raemy, Elena; Lamacchia, Céline; Gabay, Cem; Finckh, Axel; Strowig, Till

doi:10.1136/annrheumdis-2018-214514

Cited by 310 publications

(248 citation statements)

References 20 publications

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“…In humans, sequencing studies showed differences in the gut microbiome of RA patients and healthy individuals, with a special focus on the bacterium Prevotella copri ( Pc ), which was found to be relatively abundant in the gut of early RA patients . Prevotella species were furthermore found to be abundant in the gut of at‐risk individuals . Although it was hypothesized that one of Pc's antigens could be citrullinated and targeted by ACPA, at the moment there is a lack of conclusive data linking Pc with AMPA.…”

Section: Hypotheses Elucidating Mechanisms Of Autoimmunity In Ramentioning

confidence: 99%

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Autoantibodies and B Cells: The ABC of rheumatoid arthritis pathophysiology

Volkov

Schie

Woude

2019

Immunological Reviews

112

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Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation. In the last few decades, new insights into RA‐specific autoantibodies and B cells have greatly expanded our understanding of the disease. The best‐known autoantibodies in RA—rheumatoid factor (RF) and anti‐citrullinated protein antibodies (ACPA)—are present long before disease onset, and both responses show signs of maturation around the time of the first manifestation of arthritis. A very intriguing characteristic of ACPA is their remarkably high abundance of variable domain glycans. Since these glycans may convey an important selection advantage of citrulline‐reactive B cells, they may be the key to understanding the evolution of the autoimmune response. Recently discovered autoantibodies targeting other posttranslational modifications, such as anti‐carbamylated and anti‐acetylated protein antibodies, appear to be closely related to ACPA, which makes it possible to unite them under the term of anti‐modified protein antibodies (AMPA). Despite the many insights gained about these autoantibodies, it is unclear whether they are pathogenic or play a causal role in disease development. Autoreactive B cells from which the autoantibodies originate have also received attention as perhaps more likely disease culprits. The development of autoreactive B cells in RA largely depends on the interaction with T cells in which HLA “shared epitope” and HLA DERAA may play an important role. Recent technological advances made it possible to identify and characterize citrulline‐reactive B cells and acquire ACPA monoclonal antibodies, which are providing valuable insights and help to understand the nature of the autoimmune response underlying RA. In this review, we summarize what is currently known about the role of autoantibodies and autoreactive B cells in RA and we discuss the most prominent hypotheses aiming to explain the origins and the evolution of autoimmunity in RA.

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Section: Hypotheses Elucidating Mechanisms Of Autoimmunity In Ramentioning

confidence: 99%

“…143,145 Prevotella species were furthermore found to be abundant in the gut of at-risk individuals. 146 Although it was hypothesized that one of Pc's antigens could be citrullinated and targeted by ACPA, 147 at the moment there is a lack of conclusive data linking Pc with AMPA.…”

Section: Microbiome and Citrullinated Antigensmentioning

confidence: 99%

Autoantibodies and B Cells: The ABC of rheumatoid arthritis pathophysiology

Volkov

Schie

Woude

2019

Immunological Reviews

112

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“…More recently, patients at risk of RA showed an enrichment of Prevotella spp. in stools samples compared with controls .…”

Section: Phase 2: Preclinical Ramentioning

confidence: 99%

Individuals at risk of seropositive rheumatoid arthritis: the evolving story

Rantapää-Dahlqvist

Andrade

2019

J Intern Med

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The aetiology of the autoimmune disease rheumatoid arthritis (RA) involves a complex interplay between genetic and environmental factors that initiate many years before the onset of clinical symptoms. These interactions likely include both protective and susceptibility factors which together determine the risk of developing RA. More than 100 susceptibility loci have been linked to RA. The strongest association is with HLA‐DRB1 alleles encoding antigen presenting molecules containing a unique sequence in the peptide‐binding grove called the ‘shared epitope’. Female sex, infections during childhood, lifestyle habits (e.g. smoking and diet) and distinct microbial agents, amongst many others, are interacting risk factors thought to contribute to RA pathogenesis by dysregulating the immune system in individuals with genetic susceptibility. Interestingly, patients with RA develop autoantibodies many years before the clinical onset of disease, providing strong evidence that the lack of tolerance to arthritogenic antigens is amongst the earliest events in the initiation of seropositive RA. Here, we will discuss the clinical and mechanistic evidence surrounding the role of different environmental and genetic factors in the phases leading to the production of autoantibodies and the initiation of symptomatic RA. Understanding this complexity is critical in order to develop tools to identify drivers of disease initiation and propagation and to develop preventive therapeutics.

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“…In addition, high levels of genomic diversity within Prevotella strains of the same species have been observed ( 3 ), which adds another layer of complexity for predicting the effects of Prevotella strains. Recent studies have linked higher intestinal abundance of P. copri to rheumatoid arthritis ( 4-6 ), metabolic syndrome ( 7 ), low-grade systemic inflammation ( 7 ) and inflammation in the context of human immunodeficiency virus (HIV) infection ( 8-10 ), suggesting that some Prevotella strains may trigger and/or worsen inflammatory diseases ( 1, 11, 12 )…”

Section: Introductionmentioning

confidence: 99%

Specific targeting of intestinalPrevotella copriby aListeria monocytogenesbacteriocin

Rolhion

Chassaing

Nahori

et al. 2019

Preprint

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Deciphering the specific function of every microorganism in microbial gut communities is a key issue to interrogate their role during infection. Here, we report the discovery of a Listeria bacteriocin, Lmo2776, that specifically targets the abundant gut commensal Prevotella copri and affects Listeria infection. Oral infection of conventional mice with a Δlmo2776 mutant leads to a thinner intestinal mucus layer and higher Listeria loads both in the intestinal content and deeper tissues compared to WT Listeria, while no difference is observed in germ-free mice. This microbiota-dependent effect is phenocopied by precolonization of germ-free mice before Listeria infection, with P. copri, but not with other commensals,. Together, these data unveil a role for Prevotella in controlling intestinal infection, highlighting that pathogens may selectively deplete microbiota to avoid excessive inflammation.

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Prevotella copri in individuals at risk for rheumatoid arthritis

Cited by 310 publications

References 20 publications

Autoantibodies and B Cells: The ABC of rheumatoid arthritis pathophysiology

Autoantibodies and B Cells: The ABC of rheumatoid arthritis pathophysiology

Individuals at risk of seropositive rheumatoid arthritis: the evolving story

Specific targeting of intestinalPrevotella copriby aListeria monocytogenesbacteriocin

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