Disease ⇒ Rheumatoid Arthritis {40000107}

Record Keys
Type:	Disease
Parent:	[ ]
Definition:	Rheumatoid Arthritis

Details
Initialisation date:	2019-06-16
Other Terms:	RA

Links
Wickipedia Merck Manual

Meta Information
MedDra ID:	10039073
MedDra Level:	pt
ICD:	[ ]
Category:	Musculoskeletal, Rheumatology, Immunology
Zone:	[ ]
Mechanism:	[ ]

Notes:

- ACPA generation may be associated with larger populations of Prevotellaceae in both oral and intestinal microbiomes. In response to such altered microbial flora, certain predisposed individuals may develop auto-inflammatory disease, through mechanisms that may include the generation of cyclic citrullinated peptides or Th17 cell activation in the intestinal mucosa. (4)

Shared Reference Notes

[1.1]
- Porphyromonas gingivalis is a leading pathogen in chronic periodontitis, a disease process involving progressive destruction of the tissues that support the teeth. Recently, the organism has been reported to produce a unique bacterial enzyme, P. gingivalis peptidyl-arginine deiminase (PPAD), which has the ability to convert arginine residues in proteins to citrulline. Protein citrullination alters protein structure and function; hence, PPAD may be involved in deregulation of the host signalling network and immune evasion.
[1.2]
- Prevotella is a crucial genus in the onset of other chronic inflammatory disorders such as rheumatoid arthritis - Ther is a strong association between Prevotella copri and new-onset untreated rheumatoid arthritis and the higher abundance of Prevotella was associated with a reduction in several beneficial microbes, including Bacteroides.
[1.3]
- In a region in Eastern India endemic for lymphatic filariasis caused by filarial worms, not a single person with rheumatoid arthritis (RA) tested positive for circulating filarial antigens - Much higher proportion (40%) of people without RA tested positive for the nematode.
[1.4] [#Crohn’s disease, #Multiple Sclerosis]
- Significantly lower abundances of Coprococcus in CD, Dialister in MS, and Roseburia in RA.
- Significantly lower abundances of Coprococcus in CD, Dialister in MS, and Roseburia in RA.
[1.5]
- reduced abundance of Desulfovibrionaceae Bilophila, Akkermansia, and Veillonellaceae Dialister and increased levels of Lachnospiraceae Clostridium as most predictive of disease state. - increased Clostridiaceae Clostridium and Lachnospiraceae and reduced Erysipelotrichaceae were three of the eight identified in all RA models.
[1.6]
- Abundance of specific gut bacterial taxa and their genes enhances the clinical response to orthologs related to purine and methotrexate metabolism.
[1.7] [#Porphyromonas gingivalis]
- The presence of P. gingivalis in the GI microbiota has been linked with a milieu of inflammatory/autoimmune diseases associated with GI dysbiosis including RA and NAFLD
[1.8]
- Patients with RA showed an altered metabolic capacity for transporting zinc and copper. The study authors suggest that these alterations may significantly influence the perpetuations of the autoimmunity of RA. - Porphyromonas gingivalis (discussed within “Periodontal Microbiome and ACPA” section), Proteus mirabilis, Mycobacterium tuberculosis, and Mycoplasma spp are associated with an increased risk of RA development.
[1.9]
- Increased serum levels of the antibodies IgM rheumatoid factor (IgM-RF) and antibodies against #Citrullinated Proteins (ACPA) in healthy individuals imply an elevated risk of developing RA - The possible role of #Porphyromonas gingivalis in the immunopathogenesis of RA has been of particular interest due to its capacity to generate #Citrullinated Proteins.
- #Prevotella in saliva is at higher relative abundance compared to healthy controls.
- RA > #Veillonella in saliva and tongue coating is at higher relative abundance compared to healthy controls.
[1.11]
[1.12] [#Lipopolysaccharide]
- RA patients display increased levels of serum markers of gut permeability and damage and cellular gut-homing markers, both parameters (LPB, LPS, and I-FABP) positively correlating with disease severity. - Arthritic mice display increased gut permeability from early stages of disease, as well as bacterial translocation, inflammatory gut damage, increases in interferon γ (IFNγ)+ and decreases in IL-10+ intestinal-infiltrating leukocyte frequency, and reduced intestinal epithelial IL-10R expression. - Both arthritogenic bacteria and leukocytes are required to disrupt gut-barrier integrity. - Exposing intestinal organoids to IFNγ reduces IL-10R expression by epithelial cells and that mice lacking epithelial IL-10R display increased intestinal permeability and exacerbated arthritis. - Treatment of mice with AT-1001, a molecule that prevents development of gut permeability, ameliorates arthritis.
[1.13]
[1.14] [#Chronic periodontitis, #Periodontal disease]
- #Aggregatibacter actinomycetemcomitans (Aa) is a Gram-negative coccobacillus recognized as a pathogen in periodontitis and infective endocarditis. By producing a toxin (#Leukotoxin A, LtxA) that triggers global hypercitrullination in neutrophils, Aa has been recently linked to rheumatoid arthritis. - Aa has been proposed as a link between periodontitis and autoimmunity in rheumatoid arthritis (RA) due to its ability to induce citrullinated autoantigens targeted by anti-citrullinated protein antibodies (ACPAs).
[1.15]
- #Collinsella is increased in patients with rheumatoid arthritis and is associated with increased gut permeability.
[1.16]
-IgG and IgA autoantibodies from individuals who are at risk for RA cross-react against gut bacteria in the #Lachnospiraceae and #Ruminococcaceae families. - Analysis identified a bacterial strain from the #Subdoligranulum genus that was associated with autoantibody development. - Mice colonized with this #Subdoligranulum isolate developed arthritis with pathology similar to human RA.
[1.17] [#Colorectal cancer, #Crohn’s disease] [#Bacteriophage, #Western-style diet]
- the abundance of a class of crAss-like phages, a group of related viruses that includes some of the most abundant viruses of the human gut, were higher in populations with non-westernized dietary habits - several types of crAss-like phages were present at decreased levels in people with rheumatoid arthritis, #Systemic lupus erythematosus, #Ulcerative Colitis and Crohn disease, and at increased levels in people with colon cancer.
[1.18] [#Bifidobacterium pseudocatenulatum] [#Secondary bile acids] [#Probiotic Bifidobacterium pseudocatenulatum]
- In a collagen-induced arthritis (CIA) mouse model, B. pseudocatenulatum prevented joint damage by protecting the intestinal barrier and reshaped gut microbial composition, thereby elevating bile salt hydrolase (BSH) enzyme activity and increasing the levels of unconjugated secondary BAs to suppress aberrant T-helper 1/17-type immune responses
[1.19]
- IgG and IgA autoantibodies from individuals who are at risk for RA cross-react against gut bacteria in the #Lachnospiraceae and #Ruminococcaceae families. - RA > a bacterial strain from the Subdoligranulum genus (#Subdoligranulum didolesgii) that was associated with autoantibody development.
[#Calprotectin] - High cCLP serum levels are associated with worse structural outcomes in rheumatoid arthritis and to a lesser extent, in #Spondyloarthritis.
[1.21] [#Gingipains]
- #Porphyromonas gingivalis is a major pathogenic bacterium involved in the pathogenesis of periodontitis. Citrullination has been reported as the underlying mechanism of the pathogenesis, which relies on the interplay between two virulence factors of the bacterium, namely gingipain R and the bacterial peptidyl arginine deiminase. - Gingipain R cleaves host proteins to expose the C-terminal arginines for peptidyl arginine deiminase to citrullinate and generate #Citrullinated Proteins. - Citrullinating proteins present in the host synovial tissues, atherosclerotic plaques and neurons. - both virulence factors are the key factors that trigger distal effects mediated by citrullination, leading to the development of some non-communicable diseases, such as rheumatoid arthritis, #Atherosclerosis, and #Alzheimer’s disease.
[1.22]
- overabundance of #Prevotella copri in early RA patients - proliferation of the genus Collinsela and some #Lactobacillus species. - Three mechanisms by which microbiota may contribute to RA pathogenesis were proposed: inflammatory responses (#Prevotella copri and #Lactobacillus), molecular mimicry (#Prevotella copri) and loss of intestinal barrier integrity (#Collinsella).
[1.23]
- Patients with rheumatoid arthritis, #Cancer, autoimmune diseases or other chronic inflammatory conditions are predisposed to #Depression.
[1.24]
- #Periodontal disease is more common in individuals with rheumatoid arthritis (RA) who have detectable anti-citrullinated protein antibodies (ACPAs). - Citrullination is the conversion of the amino acid arginine into the non-proteinogenic amino acid citrulline. - Patients with RA and #Periodontal disease experienced repeated oral bacteremias associated with transcriptional signatures of specific monocytes, recently identified in inflamed RA synovia and blood of those with RA flares. - The oral bacteria observed transiently in blood were broadly citrullinated in the mouth, and their in situ citrullinated epitopes were targeted by extensively somatically hypermutated ACPA B Cells encoded by RA blood plasmablasts.
[1.25] [#Prevotella amnii, #Prevotella corporis, #Prevotella denticola, #Prevotella disiens, #Prevotella marshii]
- #Prevotella predominates in the intestinal microbiome in the preclinical phase of rheumatoid arthritis, promoting pathological progression in a TH17 cell-dependent manner. - gut microbiome from rheumatoid arthritis patients > five species that belong to the #Prevotella (i.e., P. denticola, P. marshii, P. disiens, P. corporis, and P. amnii)
[1.26] [#Parabacteroides distasonis]
- The relative abundance of P. distasonis in new-onset patients with RA and patients with RA with history of the disease was downregulated and this decrease was negatively correlated with Disease Activity Score-28 (DAS28)
[#Parabacteroides distasonis] - Oral treatment of arthritic mice with live P. distasonis (LPD) considerably ameliorated RA pathogenesis. - LPD-derived #Lithocholic acid (LCA), #Deoxycholic acid (DCA), #Isolithocholic acid (isoLCA) and #3-oxolithocholic acid (3-oxoLCA) had similar and synergistic effects on the treatment of RA. - A specific synthetic inhibitor of bile salt hydrolase attenuated the antiarthritic effects of LPD by reducing the production of these four bile acids.
[1.27]
- When compared with controls, participants with RA had increased levels of the #Collinsella aerofaciens species and #Enterococcus genera. Likewise, an increase of arginine deaminase activity was observed, which belonged, in approximately 90%, to the RA genes of the genus Collinsela.

References Notes

[ ]

↥ Microbiota

‐ Actinomyces Saliva Human [1.28]

‐ Actinomyces Stool Human [1.29]

‐ Actinomyces Subgingival plaque Human [1.30]

‐ Aerococcaceae Nasal swab Human [1.31]

‐ Aggregatibacter actinomycetemcomitans Causal? Oral & Gut Lumen Human

‐ Agrobacterium Synovial tissue Human [1.32]

‐ Anaerofilum Stool Human [1.33]

‐ Anaeroglobus Oral swab Human [1.34]

‐ Bacteroides sartorii Stool Human [1.35]

‐ Campylobacter Stool Human [1.36]

‐ Clostridium perfringens Stool Human [1.37]

‐ Clostridium Stool Human [1.36]

‐ Collinsella aerofaciens Gut Lumen Human

‐ Collinsella Deteriorative Stool Human [1.15, 1.22, 1.38]

‐ Comamonas Synovial tissue Human [1.32]

‐ Corynebacterium matruchotii Subgingival plaque Human [1.30]

‐ Desulfovibrionaceae Stool Human [1.39]

‐ Eggerthella lenta Stool Human [1.38]

‐ Eggerthella Stool Human [1.29]

‐ Epsilonproteobacteria Stool Human [1.36]

‐ Faecalibacterium Stool Human [1.38]

‐ Faecalicoccus Stool Human [1.29]

‐ Fusobacterium Saliva Human [1.28]

‐ Gardnerella vaginalis Stool Human [1.35]

‐ Gemella Stool Human [1.29]

‐ Granulicatella Saliva Human [1.28]

‐ Haemophilus parainfluenzae Synovial fluid Human [1.32]

‐ Haemophilus Saliva Human [1.28]

‐ Halomonas Blood Human [1.40]

‐ Klebsiella Stool Human [1.39]

‐ Kocuria Synovial tissue Human [1.32]

‐ Lactobacillaceae Stool Human [1.41]

‐ Lactobacillus Stool Human [1.22, 1.42]

‐ Lautropia Saliva Human [1.28]

‐ Leptotrichia Saliva Human [1.28]

‐ Meiothermus Synovial tissue Human [1.32]

‐ Neisseriaceae Nasal swab Human [1.31]

‐ Neisseria Saliva Human [1.28]

‐ Planococcaceae Nasal swab Human [1.31]

‐ Porphyromonas gingivalis Causal? Gut Lumen Human

‐ Porphyromonas gingivalis Tongue scrape sample Human [1.43]

‐ Porphyromonas somerae Stool Human [1.35]

‐ Porphyromonas Saliva Human [1.28]

‐ Prevotella amnii Stool Human [1.35]

‐ Prevotella copri Stool Human [1.22, 1.44]

‐ Prevotella copri Synovial fluid Human [1.32]

‐ Prevotella corporis Stool Human [1.35]

‐ Prevotella denticola Stool Human [1.35]

‐ Prevotella disiens Stool Human [1.35]

‐ Prevotella marshii Stool Human [1.35]

‐ Prevotella melaninogenica Saliva Human [1.28]

‐ Prevotellaceae Causal? Gut Lumen Human

‐ Prevotella Oral swab Human [1.34]

‐ Prevotella Saliva Human [1.45]

‐ Proteus mirabilis Gut Lumen Human

‐ Rhodoplanes Synovial tissue Human [1.32]

‐ Rothia Saliva Human [1.28]

‐ Rothia Stool Human [1.29]

‐ Selenomonas Oral swab Human [1.34]

‐ Selenomonas Saliva Human [1.45]

‐ Shewanella Blood Human [1.40]

‐ Staphylococcus aureus Nasal swab Human [1.31]

‐ Streptococcus Saliva Human [1.28]

‐ Streptococcus Stool Human [1.29]

‐ Streptococcus Subgingival plaque Human [1.30]

‐ Subdoligranulum didolesgii Causal? Stool Human [1.19]

‐ Subdoligranulum Causal? Stool Mouse [1.16]

‐ Succinivibrionaceae Stool Human [1.39]

‐ Treponema amylovorum Synovial fluid Human [1.32]

‐ Veillonella dispar Saliva Human [1.28]

‐ Veillonella dispar Synovial fluid Human [1.32]

‐ Veillonellaceae Nasal swab Human [1.31]

‐ Veillonella Subgingival plaque Human [1.30]

↧ Microbiota

‐ Achromobacter Blood Human [1.40]

‐ Acinetobacter Saliva Human [1.28]

‐ Anaerofustis Stool Human [1.29]

‐ Bacteroides fragilis Stool Human [1.46]

‐ Bacteroides Saliva Human [1.28]

‐ Bifidobacteriaceae Stool Human [1.39]

‐ Bifidobacterium Stool Human [1.46]

‐ Brevundimonas Saliva Human [1.28]

‐ Capnocytophaga Oral swab Human [1.34]

‐ Chryseobacterium Saliva Human [1.28]

‐ Collinsella Deteriorative Stool Human [1.47]

‐ Comamonas Saliva Human [1.28]

‐ Coriobacteriaceae Stool Human [1.47]

‐ Corynebacterium Blood Human [1.40]

‐ Corynebacterium Oral swab Human [1.34]

‐ Defluviitalea Saliva Human [1.45]

‐ Enhydrobacter Saliva Human [1.28]

‐ Erysipelotrichaceae Stool Human [1.47]

‐ Eubacterium rectale Stool Human [1.46]

‐ Eubacterium yurii Saliva Human [1.45]

‐ Gemella Blood Human [1.40]

‐ Gemmiger Stool Human [1.29]

‐ Granulicatella Blood Human [1.40]

‐ Haemophilus Saliva Human [1.45]

‐ Lachnospira Stool Human [1.29]

‐ Leptotrichia Oral swab Human [1.34]

‐ Moraxellaceae Nasal swab Human [1.31]

‐ Mycoplana Saliva Human [1.28]

‐ Neisseria oralis Saliva Human [1.45]

‐ Oxalobacteraceae Stool Human [1.39]

‐ Parvimonas Saliva Human [1.45]

‐ Prevotella Subgingival plaque Human [1.30]

‐ Pseudomonas Saliva Human [1.28]

‐ Roseburia faecis Stool Human [1.39]

‐ Roseburia Gut Lumen Human

‐ Roseburia Stool Human [1.29]

‐ Selenomonas Subgingival plaque Human [1.30]

‐ Serratia Blood Human [1.40]

‐ Shigella Blood Human [1.40]

‐ Sphingomonas yabuuchiae Saliva Human [1.28]

‐ Sphingomonas Saliva Human [1.28]

‐ Sporobacter Stool Human [1.29]

‐ Staphylococcaceae Nasal swab Human [1.31]

‐ Staphylococcus Blood Human [1.40]

‐ Stenotrophomonas Saliva Human [1.28]

‐ Streptococcus Blood Human [1.40]

‐ Tissierellaceae Nasal swab Human [1.31]

‐ Wautersiella Saliva Human [1.28]

Disease ⇒ Rheumatoid Arthritis {40000107}

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References Notes

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