Immunofluorescent demonstration of intracellular fibrin in synovial tissue.

Andersen, Rune; P, Elling

doi:10.1136/ard.31.1.59

Cited by 16 publications

(6 citation statements)

References 8 publications

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“…1) showed that 1) the interstitial amorphous deposits stained by the latter Ab correspond to fibrin and 2) most of the intracellular deiminated material does not correspond to fibrin since the number of cells stained by the 311 mAb was far smaller than the number of cells stained by the Ab to citrulline. These results confirmed the presence of extracellular and intracellular fibrin(ogen) material in rheumatoid synovium (23,24) and, in perfect agreement with the immunochemical data, indicated that at least part of the fibrin found in RA synovial membranes is deiminated.…”

Section: Immunohistochemical Analysis Of Ra Synovial Membranes Confirsupporting

confidence: 88%

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The Major Synovial Targets of the Rheumatoid Arthritis-Specific Antifilaggrin Autoantibodies Are Deiminated Forms of the α- and β-Chains of Fibrin

Masson-Bessière

Sebbag

Girbal-Neuhauser

et al. 2001

The Journal of Immunology

582

502

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IgG antifilaggrin autoantibodies (AFA) are the most specific serological markers of rheumatoid arthritis. In epithelial tissues, they recognize citrulline-bearing epitopes present on various molecular forms of (pro)filaggrin. Histological analysis of rheumatoid synovial membranes with an Ab to citrulline showed labeling of interstitial amorphous deposits and mononuclear cells of various types. Immunochemical analysis of exhaustive sequential extracts of the same tissues showed that they contain several deiminated (citrulline containing) proteins. Among them, two proteins, p64–78 and p55–61, present in urea-DTT and guanidine extracts, were shown by immunoblotting to be specifically targeted by AFA. By amino-terminal sequencing the proteins were identified as deiminated forms of the α- and β-chains of fibrin, respectively. Their identity was confirmed using several Abs specific for the Aα- and/or to the Bβ-chain of fibrin(ogen). Moreover, AFA-positive rheumatoid arthritis (RA) sera and purified AFA were highly reactive to the Aα- and Bβ-chains of human fibrinogen only after deimination of the molecules by a peptidylarginine deiminase. Autoantibodies affinity purified from a pool of RA sera onto deiminated fibrinogen were reactive toward all of the epithelial and synovial targets of AFA. This confirmed that the autoantibodies to the deiminated Aα-and Bβ-chains of fibrinogen, the autoantibodies to the synovial proteins p64–78 and p55–61, and, lastly, AFA, constitute largely overlapping autoantibody populations. These results show that deiminated forms of fibrin deposited in the rheumatoid synovial membranes are the major target of AFA. They suggest that autoimmunization against deiminated fibrin is a critical step in RA pathogenesis.

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Section: Immunohistochemical Analysis Of Ra Synovial Membranes Confirsupporting

confidence: 88%

“…material has long been known to be particularly prominent in rheumatoid inflammation of synovial tissue (23,24). In the RA joints, accumulation of fibrin is thought to result from an altered balance between coagulation and fibrinolysis.…”

Section: Discussionmentioning

confidence: 99%

The Major Synovial Targets of the Rheumatoid Arthritis-Specific Antifilaggrin Autoantibodies Are Deiminated Forms of the α- and β-Chains of Fibrin

Masson-Bessière

Sebbag

Girbal-Neuhauser

et al. 2001

The Journal of Immunology

582

502

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“…Recent studies have suggested that the target epitopes in synovium are citrullinated vimentin or variants of the α and β chains of fibrin that have been subjected to posttranslational deimination (50,53,(56)(57). Deposits of fibrin and fibrin-related extracellular and intracellular deposits have long been recognized in inflamed rheumatoid synovium (58). Indeed, over 40 years ago, Dumonde and Glynn induced chronic arthritis in rabbits by intraarticular injection of either heterologous or autologous fibrin into previously sensitized animals (59).…”

Section: Citrullinated Proteins Link Rheumatoid and Periodontal Inflamentioning

confidence: 98%

Hypothesis: The Humoral Immune Response to Oral Bacteria Provides a Stimulus for the Development of Rheumatoid Arthritis

et al. 2004

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Rheumatoid arthritis (RA) and adult periodontitis share common pathogenetic mechanisms and immunologic and pathological findings. One oral pathogen strongly implicated in the pathogenesis of periodontal disease, Porphyromonas gingivalis, possesses a unique microbial enzyme, peptidylarginine deiminase (PAD), the human equivalent of which has been identified as a susceptibility factor for RA. We suggest that individuals predisposed to periodontal infection are exposed to antigens generated by PAD, with de-iminated fibrin as a likely candidate, which become systemic immunogens and lead to intraarticular inflammation. PAD engendered antigens lead to production of rheumatoid factor-containing immune complexes and provoke local inflammation, both in gingiva and synovium via Fc and C5a receptors.

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“…Gingipains activate coagulation factors and degrade fibrinogen/fibrin [47]. Deposits of fibrin and fibrin-related extracellular and intracellular deposits have long been recognized in inflamed rheumatoid synovium [48]. However, in RA, other proteinase (e.g., metalloproteinase) degrade fibrinogen/fibrin.…”

Section: Fibrinmentioning

confidence: 98%

Rheumatoid arthritis is linked to oral bacteria: etiological association

Öğrendik

2009

Mod Rheumatol

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The purpose of this review is to evaluate the association between rheumatoid arthritis (RA) and periodontopathic bacteria. Clinical studies of RA and periodontal disease have provided evidence for a significant association between the two disorders. Patients with long-standing active RA have a substantially increased frequency of periodontal disease compared with that among healthy subjects. High levels of oral anaerobic bacterial antibodies have been found in the serum and synovial fluid of RA patients. Porphyromonas gingivalis, Tannerella forsythensis, and Prevotella intermedia have been identified in RA synovial fluid. Ornidazole, levofloxacin, and clarithromycin are used in the treatment of infections caused by anaerobic bacteria. These antibiotics have been shown to be effective against RA. The evidence in this review indicates that oral bacteria directly associate with etiopathogenesis of RA.

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Immunofluorescent demonstration of intracellular fibrin in synovial tissue.

Cited by 16 publications

References 8 publications

The Major Synovial Targets of the Rheumatoid Arthritis-Specific Antifilaggrin Autoantibodies Are Deiminated Forms of the α- and β-Chains of Fibrin

The Major Synovial Targets of the Rheumatoid Arthritis-Specific Antifilaggrin Autoantibodies Are Deiminated Forms of the α- and β-Chains of Fibrin

Hypothesis: The Humoral Immune Response to Oral Bacteria Provides a Stimulus for the Development of Rheumatoid Arthritis

Rheumatoid arthritis is linked to oral bacteria: etiological association

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