Relationship between air pollution and positivity of RA-related autoantibodies in individuals without established RA: a report on SERA

Gan, Ryan W.; Deane, Kevin D.; Zerbe, Gary O.; Demoruelle, M. Kristen; Weisman, Michael H.; Buckner, Jane H.; Gregersen, Peter K.; Mikuls, Ted R.; O'Dell, James Robert; Keating, Richard M.; Holers, V. Michael; Norris, Jill M.

doi:10.1136/annrheumdis-2012-202949

Cited by 49 publications

(29 citation statements)

References 18 publications

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“…However, the findings have been mixed, perhaps in part due to the complexity of assessing the true exposure to air pollution as well as accounting for other factors such as specific components of pollution that may vary by locality. In addition, these findings are likely affected by confounders such as increased lower socioeconomic status, a purported risk factor for RA in its own right, in individuals who are also exposed to greater amounts of pollution (69–75). …”

Section: Environmental Risk Factors For Ramentioning

confidence: 99%

Genetic and environmental risk factors for rheumatoid arthritis

Deane

Demoruelle

Kelmenson

et al. 2017

Best Practice & Research Clinical Rheumatology

441

296

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Multiple genetic and environmental factors have been associated with an increased risk for rheumatoid arthritis (RA). Of these, the strongest associations have been seen with female sex, a family history of RA, the genetic factor the ‘shared epitope’ and with exposure to tobacco smoke. There is also renewed interest in mucosal inflammation and microbial factors as contributors to the development of RA. However, the identification of a ‘preclinical’ period of RA that can be defined as local or systemic autoimmunity as measured by autoantibodies and other biomarkers prior to the development of clinically-apparent synovitis suggests that the risk factors for RA are acting long prior to first clinical evidence of IA. As such, a major challenge to the field will be to investigate the full spectrum of the development of RA, from initiation and propagation of autoimmunity during preclinical RA and transition to clinically-apparent synovitis and classifiable RA, in order to determine which genetic and environmental factors are important at each stage of disease development. Understanding the exact role and timing of action of risk factors for RA is especially important given the advent of prevention trials in RA, and the hope that a full understanding of genetic and environmental factors in RA could lead to effective preventive interventions.

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Section: Environmental Risk Factors For Ramentioning

confidence: 99%

Genetic and environmental risk factors for rheumatoid arthritis

Deane

Demoruelle

Kelmenson

et al. 2017

Best Practice & Research Clinical Rheumatology

441

296

View full text Add to dashboard Cite

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“…Cigarette smoking leads to increased expression of PAD and protein citrullination in the bronchoalveolar lavage cells of smokers without arthritis 137 . Additionally, PAD polymorphisms, such as PADI4, have been shown to predispose male smokers to developing RA 138 . ACPAs and rheumatoid factor have also been found in induced sputa of patients with early-stage RA 139 .…”

Section: Rheumatoid Arthritismentioning

confidence: 99%

How the microbiota shapes rheumatic diseases

et al. 2016

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The human gut harbours a tremendously diverse and abundant microbial community that correlates with, and even modulates, many health-related processes. The mucosal interfaces are particularly active sites of microorganism-host interplay. Growing insight into the characteristic composition and functionality of the mucosal microbiota has revealed that the microbiota is involved in mucosal barrier integrity and immune function. This involvement affects proinflammatory and anti-inflammatory processes not only at the epithelial level, but also at remote sites such as the joints. Here, we review the role of the gut microbiota in shaping local and systemic immune responses and how disturbances in the host-microorganism interplay can potentially affect the development and progression of rheumatic diseases. Increasing our understanding of how to promote host-microorganism homeostasis could therefore reveal novel strategies for the prevention or alleviation of rheumatic disease.

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“…This association appears to be cigarette smoking specific since non-smoking particulate matter (i.e. a measure of air pollution) was not associated with increased risk of progression to RA in asymptomatic seropositive patients [61]. …”

Section: Airway Inflammation and Ra – A Role For The Microbiome?mentioning

confidence: 99%

Microbiome and mucosal inflammation as extra-articular triggers for rheumatoid arthritis and autoimmunity

Brusca

Abramson

Scher

2014

Current Opinion in Rheumatology

200

169

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Purpose of Review Despite progress towards understanding the molecular pathogenesis of Rheumatoid Arthritis (RA), its etiology remains elusive. Genes are important but rather insufficient to explain the majority of RA cases. This review describes novel data supporting the microbiome and its interactions with the human host as potential en(‘in’)vironmental factors in RA pathogenesis. Recent Findings Animal models of inflammatory arthritis have shown that the presence of bacteria in mucosal surfaces is sufficient to alter local and systemic host immune responses and elicit joint inflammation. Human RA studies have focused on three mucosal sites: the gut, the gingival, and the respiratory tree. The oral microbiome, and specifically Porphyromonas gingivalis (P. gingivalis), has long been implicated. Novel sequencing technologies have allowed investigations into the role of the gut microbiome in the development of autoimmune arthritis. Most recently, the pulmonary parenchyma has also been described as yet another possible mucosal site of initiation of autoimmunity in RA. Summary Emerging data implicates the microbiome in RA pathogenesis. Mucosal sites exposed to a high load of bacterial antigens - such as the periodontium, lung, and gut - may represent the initial site of autoimmune generation. If validated, these findings could lead to the discovery of potential biomarkers and therapeutic approaches in the pre-clinical and clinical phases of RA.

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Relationship between air pollution and positivity of RA-related autoantibodies in individuals without established RA: a report on SERA

Cited by 49 publications

References 18 publications

Genetic and environmental risk factors for rheumatoid arthritis

Genetic and environmental risk factors for rheumatoid arthritis

How the microbiota shapes rheumatic diseases

Microbiome and mucosal inflammation as extra-articular triggers for rheumatoid arthritis and autoimmunity

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