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Rheumatoid Arthritis

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The Microbiome in Rheumatic Diseases and Infection

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with both environmental and genetic factors but of unknown cause. There are >100 associated gene loci, the most significant of which is HLA-DRB1 in the major histocompatibility complex region. Recent work has also highlighted important roles of the human mucosal microbiota, at both the gingival as well as the intestinal surfaces. Periodontal disease and alterations in the gingival microbiota, including overgrowth of Porphyromonas gingivalis, are associated with RA. A key hallmark of RA is serum anti-citrullinated protein antibodies reactive against a variety of posttranslationally citrullinated proteins, which are enriched in RA, particularly in patients with HLA-DRB1 risk alleles. Citrullination of arginine residues is catalyzed by peptidylarginine deiminases (PADs). Of note, P. gingivalis produces its own PAD enzyme (PPAD), which may contribute to the citrullination of native proteins. Differences in the intestinal microbiota, particularly overgrowth of Prevotella copri, are associated with early RA, perhaps compensating for the absence of HLA-DRB1 risk alleles in some patients. As the role of the microbiota in RA is elucidated, targeted interventions to manipulate the microbiome to prevent or treat RA may emerge.

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Abbreviations

ACPA:

Anti-cyclic citrullinated peptide antibody

CRA:

Chronic rheumatoid arthritis

DAS:

Disease activity score

DC:

Dendritic cells

HC:

Healthy control

IL:

Interleukin

JIA:

Juvenile idiopathic arthritis

MMP:

Matrix metalloproteinase

NORA:

New-onset rheumatoid arthritis

NSAID:

Nonsteroidal anti-inflammatory drug

OA:

Osteoarthritis

PAD:

Peptidylarginine deiminase

PD:

Periodontal disease

PPAD:

P. gingivalis peptidylarginine deiminase

RA:

Rheumatoid arthritis

SE:

Shared epitope

SRP:

Scaling and root planning

TNFi:

Tumor necrosis factor inhibitor

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Authors and Affiliations

  1. University of Alabama at Birmingham, Department of Pediatrics, Birmingham, AL, USA

    Matthew L. Stoll

  2. Division of Clinical Immunology and Rheumatology, Comprehensive Arthritis, Musculoskeletal, Bone, and Autoimmunity Center, UAB, The University of Alabama at Birmingham, Birmingham, AL, USA

    S. Louis Bridges Jr.

  3. University of Alabama at Birmingham, Division of Clinical Immunology and Rheumatology, Birmingham, AL, USA

    Maria I. Danila

Authors
  1. Matthew L. Stoll
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  2. S. Louis Bridges Jr.
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  3. Maria I. Danila
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Correspondence to Matthew L. Stoll .

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Editors and Affiliations

  1. Faculty of Medicine, Cairo University, Cairo, Egypt

    Gaafar Ragab

  2. University of Alabama, Birmingham, Alabama, USA

    T. Prescott Atkinson

  3. University of Alabama, Birmingham, Alabama, USA

    Matthew L. Stoll

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Stoll, M.L., Bridges, S.L., Danila, M.I. (2018). Rheumatoid Arthritis. In: Ragab, G., Atkinson, T., Stoll, M. (eds) The Microbiome in Rheumatic Diseases and Infection. Springer, Cham. https://doi.org/10.1007/978-3-319-79026-8_15

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