PMID- 32582191
OWN - NLM
STAT- MEDLINE
DCOM- 20210405
LR  - 20210405
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 11
DP  - 2020
TI  - Infectious Triggers in Periodontitis and the Gut in Rheumatoid Arthritis (RA): A 
      Complex Story About Association and Causality.
PG  - 1108
LID - 10.3389/fimmu.2020.01108 [doi]
LID - 1108
AB  - Rheumatoid arthritis (RA) is a systemic immune mediated inflammatory disease of 
      unknown origin, which is predominantly affecting the joints. Antibodies against 
      citrullinated peptides are a rather specific immunological hallmark of this 
      heterogeneous entity. Furthermore, certain sequences of the third hypervariable 
      region of human leukocyte antigen (HLA)-DR class II major histocompatibility 
      (MHC) molecules, the so called "shared epitope" sequences, appear to promote 
      autoantibody positive types of RA. However, MHC-II molecule and other genetic 
      associations with RA could not be linked to immune responses against specific 
      citrullinated peptides, nor do genetic factors fully explain the origin of RA. 
      Consequently, non-genetic factors must play an important role in the complex 
      interaction of endogenous and exogenous disease factors. Tobacco smoking was the 
      first environmental factor that was associated with onset and severity of RA. 
      Notably, smoking is also an established risk factor for oral diseases. 
      Furthermore, smoking is associated with extra-articular RA manifestations such as 
      interstitial lung disease in anatomical proximity to the airway mucosa, but also 
      with subcutaneous rheumatoid nodules. In the mouth, Porphyromonas gingivalis is a 
      periodontal pathogen with unique citrullinating capacity of foreign microbial 
      antigens as well as candidate RA autoantigens. Although the original hypothesis 
      that this single pathogen is causative for RA remained unproven, epidemiological 
      as well as experimental evidence linking periodontitis (PD) with RA is rapidly 
      accumulating. Other periopathogens such as Aggregatibacter actinomycetemcomitans 
      and Prevotella intermedia were also proposed to play a specific immunodominant 
      role in context of RA. However, demonstration of T cell reactivity against 
      citrullinated, MHC-II presented autoantigens from RA synovium coinciding with 
      immunity against Prevotella copri (Pc.), a gut microbe attracted attention to 
      another mucosal site, the intestine. Pc. was accumulated in the feces of 
      clinically healthy subjects with citrulline directed immune responses and was 
      correlated with RA onset. In conclusion, we retrieved more than one line of 
      evidence for mucosal sites and different microbial taxa to be potentially 
      involved in the development of RA. This review gives an overview of infectious 
      agents and mucosal pathologies, and discusses the current evidence for causality 
      between different exogenous or mucosal factors and systemic inflammation in RA.
CI  - Copyright (c) 2020 Moller, Kollert, Sculean and Villiger.
FAU - Moller, Burkhard
AU  - Moller B
AD  - Department for Rheumatology, Immunology and Allergology, Inselspital-University 
      Hospital of Bern, Bern, Switzerland.
FAU - Kollert, Florian
AU  - Kollert F
AD  - Department for Rheumatology, Immunology and Allergology, Inselspital-University 
      Hospital of Bern, Bern, Switzerland.
FAU - Sculean, Anton
AU  - Sculean A
AD  - Department of Periodontology, School of Dental Medicine, University of Bern, 
      Bern, Switzerland.
FAU - Villiger, Peter M
AU  - Villiger PM
AD  - Department for Rheumatology, Immunology and Allergology, Inselspital-University 
      Hospital of Bern, Bern, Switzerland.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20200603
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Autoantibodies)
RN  - 0 (Autoantigens)
SB  - IM
MH  - Animals
MH  - Arthritis, Rheumatoid/*immunology/*microbiology
MH  - Autoantibodies/immunology
MH  - Autoantigens/*immunology
MH  - Gastrointestinal Microbiome/*immunology
MH  - Humans
MH  - Mouth Mucosa/immunology/microbiology
MH  - Periodontitis/immunology/*microbiology
PMC - PMC7283532
OTO - NOTNLM
OT  - intestinal
OT  - mucosa
OT  - periodontitis
OT  - rheumatoid arthritis
OT  - trigger
EDAT- 2020/06/26 06:00
MHDA- 2021/04/07 06:00
PMCR- 2020/01/01
CRDT- 2020/06/26 06:00
PHST- 2020/02/21 00:00 [received]
PHST- 2020/05/07 00:00 [accepted]
PHST- 2020/06/26 06:00 [entrez]
PHST- 2020/06/26 06:00 [pubmed]
PHST- 2021/04/07 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2020.01108 [doi]
PST - epublish
SO  - Front Immunol. 2020 Jun 3;11:1108. doi: 10.3389/fimmu.2020.01108. eCollection 
      2020.