Human α‐enolase is immunogenic, but not arthritogenic, in HLA–DR4–transgenic mice: Comment on the article by Kinloch et al

Haag, Sabrina; Uysal, Hüseyin; Bäcklund, Johan; Tuncel, Jonatan; Holmdahl, Rikard

doi:10.1002/art.34379

Cited by 7 publications

(5 citation statements)

References 11 publications

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“…However, an arthritogenic effect could not be replicated. A possible explanation for this discrepancy may be attributed to local environmental conditions, in particular the pathogen status in different specific pathogen-free facilities [100,101].…”

Section: Microbial Factors Contributing To the Generation Of Autoimmu...mentioning

confidence: 99%

Gene, environment, microbiome and mucosal immune tolerance in rheumatoid arthritis

2014

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RA is a complex multifactorial chronic disease that transitions through several stages. Multiple studies now support that there is a prolonged phase in early RA development during which there is serum elevation of RA-related autoantibodies including RF and ACPAs in the absence of clinically evident synovitis. This suggests that RA pathogenesis might originate in an extra-articular location, which we hypothesize is a mucosal site. In discussing this hypothesis, we will present herein the current understanding of mucosal immunology, including a discussion about the generation of autoimmune responses at these surfaces. We will also examine how other factors such as genes, microbes and other environmental toxins (including tobacco smoke) could influence the triggering of autoimmunity at mucosal sites and eventually systemic organ disease. We will also propose a research agenda to improve our understanding of the role of mucosal inflammation in the development of RA.

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Section: Microbial Factors Contributing To the Generation Of Autoimmu...mentioning

confidence: 99%

Gene, environment, microbiome and mucosal immune tolerance in rheumatoid arthritis

2014

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“…Although not showing that citrullinated enolases were more reactive in the DR4-restricted model, the study demonstrated that a Pg protein could induce arthritis and propagate an immune response against citrullinated peptides. Another group conducted a similar series of experiments using citrullinated and noncitrullinated forms of human enolase in several arthritissusceptible mouse strains [88 ■ ]. Although antibodies developed against both forms, arthritis did not develop, clinically or histologically, in any of their experiments.…”

Section: Animal Studies Of Periodontal Disease and Arthritismentioning

confidence: 99%

Periodontal disease and rheumatoid arthritis

Bingham

Moni

2013

Current Opinion in Rheumatology

145

106

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Purpose of review This review was conducted to focus on the recent clinical and translational research related to the associations between periodontal disease and rheumatoid arthritis. Recent findings There is a growing interest in the associations between oral health and autoimmune and inflammatory diseases. A number of epidemiologic studies have described associations between rheumatoid arthritis and periodontal disease. Recent clinical studies continue to support these reports, and are increasingly linked with biological assessments to better understand the nature of these relationships. A number of recent studies have evaluated the periopathogenic roles of Porphyromonas gingivalis, the oral microbiome, and mechanisms of site-specific and substrate-specific citrullination. These are helping to further elucidate the interactions between these two inflammatory disease processes. Summary Studies of clinical oral health parameters, the gingival microenvironment, autoantibodies and biomarkers, and rheumatoid arthritis disease activity measures are providing a better understanding of the potential mechanisms responsible for rheumatoid arthritis and periodontal disease associations. The cumulative results and ongoing studies have the promise to identify novel mechanisms and interventional strategies to improve patient outcomes for both conditions.

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“…Although these findings suggest an important role of citrullination in the pathogenesis of RA, it has not yet been clarified whether ACPAs lead to joint inflammation. Direct induction of autoimmunity in experimental animals by citrullinated antigens has been reported for fibrinogen (), while contradicting results have been reported for α‐enolase (). It has further been shown that antibodies to citrullinated fibrinogen bind to the inflamed synovium in collagen‐induced arthritis (CIA) (), that antibodies to citrullinated vimentin induce osteoclastogenesis (), and that antibodies directed to the citrullinated C1 epitope on type II collagen (CII) mediate arthritis in mice ().…”

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confidence: 95%

Identification of New Citrulline‐Specific Autoantibodies, Which Bind to Human Arthritic Cartilage, by Mass Spectrometric Analysis of Citrullinated Type II Collagen

Haag

Schneider

Mason

et al. 2014

Arthritis & Rheumatology

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Objective. To investigate type II collagen (CII) as a joint-specific target of the anti-citrullinated protein antibody (ACPA) response in rheumatoid arthritis (RA).Methods. Potential citrullinated neoepitopes were identified by high-resolution tandem mass spectrometry (MS/MS) of in vitro peptidylarginine deiminase 2 (PAD-2)-treated CII, and the relationship between citrullination and CII conformation was investigated by circular dichroism and conformation-dependent antibodies. Based on the MS analyses, synthetic peptides were designed and analyzed for serum IgG reactivity in the Epidemiological Investigation of RA (EIRA) casecontrol cohort of 1,949 RA patients and 278 healthy controls. Peptide-specific antibodies were purified from RA patient serum and used to stain RA cartilage specimens.Results. We described the conformationdependent citrullination pattern of CII after PAD-2 treatment at room temperature and 37°C and showed that CII could be citrullinated in its native triple-helical conformation. Screening of Arg and Cit pairs of synthetic peptides revealed new citrullinated B cell epitopes on CII. Antibodies directed to 2 proximal epitopes close to the C-terminus of the CII triple helix were recognized by autoantibodies in 21% and 17% of RA patients, respectively. Affinity-purified antibodies from RA sera directed to these 2 epitopes, but not antibodies directed to citrullinated ␣-enolase peptide 1, bound to RA cartilage.Conclusion. These findings suggest that cartilagedirected anticitrulline immunity contributes to the induction of joint inflammation in RA.

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Human α‐enolase is immunogenic, but not arthritogenic, in HLA–DR4–transgenic mice: Comment on the article by Kinloch et al

Cited by 7 publications

References 11 publications

Gene, environment, microbiome and mucosal immune tolerance in rheumatoid arthritis

Gene, environment, microbiome and mucosal immune tolerance in rheumatoid arthritis

Periodontal disease and rheumatoid arthritis

Identification of New Citrulline‐Specific Autoantibodies, Which Bind to Human Arthritic Cartilage, by Mass Spectrometric Analysis of Citrullinated Type II Collagen

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