Two rheumatoid arthritis–specific autoantigens correlate microbial immunity with autoimmune responses in joints

Pianta, Annalisa; Arvikar, Sheila L.; Strle, Klemen; Drouin, Elise E.; Wang, Qi; Costello, Catherine E.; Steere, Allen C.

doi:10.1172/jci93450

Cited by 183 publications

(138 citation statements)

References 47 publications

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“…A similar finding was reported in mouse models of multiple sclerosis and autoimmune diabetes . Furthermore, a number of human studies reported mimicry between gut bacteria and candidate antigens involved in human autoimmune diseases . In line with the notion that specific antigens are being recognized by the immune system, several major histocompatibility complex molecules have been linked to various systemic and ocular autoimmune diseases .…”

Section: Commensal Bacteria and Intraocular Diseasesupporting

confidence: 77%

Visions of Eye Commensals: The Known and the Unknown About How the Microbiome Affects Eye Disease

Leger

Caspi

2018

BioEssays

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Until recently, the ocular surface is thought by many to be sterile and devoid of living microbes. It is now becoming clear that this may not be the case. Recent and sophisticated PCR analyses have shown that microbial DNA-based “signatures” are present within various ethnic, geographic, and contact lens wearing communities. Furthermore, using a mouse model of ocular surface disease, we have shown that the microbe, Corynebacterium mastitidis (C. mast), can stably colonize the ocular mucosa and that a causal relationship exists between ocular C. mast colonization and beneficial local immunity. While this constitutes proof-of-concept that a bona fide ocular microbiome that tunes immunity can exist at the ocular surface, there remain numerous unanswered questions to be addressed before microbiome-modulating therapies may be successfully developed. Here, the authors will briefly outline what is currently known about the local ocular microbiome as well as microbiomes associated with other sites, and how those sites may play a role in ocular surface immunity. Understanding how commensal microbes affect the ocular surface immune homeostasis has the potential revolutionize how we think about treating ocular surface disease.

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Section: Commensal Bacteria and Intraocular Diseasesupporting

confidence: 77%

Visions of Eye Commensals: The Known and the Unknown About How the Microbiome Affects Eye Disease

Leger

Caspi

2018

BioEssays

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“…The relationships between chronic vascular damage, tissue fibrosis, and autoimmunity seen in postinfectious LA may have broader implications for development of pathogenic autoimmunity in other conditions such as RA. An association between tissue damage signals and autoimmunity has been observed in RA (Nefla, Holzinger, Berenbaum, & Jacques, ), which may be initiated at sites of extra‐articular inflammation and tissue damage from periodontal disease within the oral cavity (Arvikar et al, ; Potempa, Mydel, & Koziel, ), dysbiosis within the gut (Pianta et al, ; Van de Wiele, Van Praet, Marzorati, Drennan, & Elewaut, ), or smoking‐related lung fibrosis (Antoniou et al, ). However, in RA, autoimmunity usually develops into a life‐long immune disorder, which does not happen in postinfectious LA, implying that in RA, antigenic triggers remain.…”

Section: Discussionmentioning

confidence: 99%

Robust interferon signature and suppressed tissue repair gene expression in synovial tissue from patients with postinfectious,Borrelia burgdorferi‐induced Lyme arthritis

Lochhead

Arvikar

Aversa

et al. 2018

Cellular Microbiology

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In most patients with Lyme arthritis (LA), antibiotic therapy results in Borrelia burgdorferi pathogen elimination, tissue repair, and return to homeostasis. However, despite spirochetal killing, some patients develop proliferative synovitis, characterised by synovial hyperplasia, inflammation, vascular damage, and fibrosis that persists for months to several years after antibiotic treatment, called postinfectious LA. In this study, we characterised the transcriptomes of postinfectious LA patients' synovial tissue, the target tissue of the immune response. High-throughput RNA sequencing to a depth of ~30 million reads per sample was used to profile gene expression in synovial tissue from 14 patients with postinfectious LA, compared with eight patients with other types of chronic inflammatory arthritis and five with minimally inflammatory osteoarthritis (OA). Synovium from postinfectious LA and other inflammatory arthritides shared gene signatures associated with antigen presentation, innate immune responses, and cell-mediated immune activation, whereas these responses were diminished in OA synovium. Unique to postinfectious LA was a particularly robust interferon-gamma (IFNγ) signature. Moreover, this heightened IFNγ signature inversely correlated with expression of genes involved in repair of damaged tissue, including genes associated with stromal cell proliferation and differentiation, neovascularisation, and extracellular matrix synthesis, which were markedly suppressed in postinfectious LA. Transcriptional observations were confirmed by cytokine profiling, histologic analyses, and clinical correlations. We propose that in patients with postinfectious LA, overexpression of IFNγ in synovium prevents appropriate repair of tissue damaged by B. burgdorferi infection, blocking return to tissue homeostasis long after completion of antibiotic therapy and resolution of active infection.

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“…Notably, the increase of Collinsella in many rheumatoid arthritis patients could be associated with a decrease of CACO2 tight junction proteins and induction of T H 17 cytokines production in in vitro experiments. A possible link between gut microbiota and immune response in rheumatoid arthritis has been suggested by Pianta et al ., who found a marked sequence homology between sulfatase proteins of some commensal bacteria and two autoantigen targets of T and B cell response in synovial tissue in RA patients . Thus, the molecular mimicry hypothesis could explain a cross‐reactive immune response that, in turn, could give rise to an autoimmune attack direct against self‐antigens and contribute to the inflammatory status.…”

Section: Microbiota and Probiotics In Autoimmune Diseasesmentioning

confidence: 99%

Gut microbiota and probiotics: novel immune system modulators in myasthenia gravis?

Rinaldi

Consonni

Guidesi³

et al. 2018

Annals of the New York Academy of Sciences

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Gut microorganisms (microbiota) live in symbiosis with the host and influence human nutrition, metabolism, physiology, and immune development and function. The microbiota prevents pathogen infection to the host, and in turn the host provides a niche for survival. The alteration of gut bacteria composition (dysbiosis) could contribute to the development of immune-mediated diseases by influencing the immune system activation and driving the pro- and anti-inflammatory responses in order to promote or counteract immune reactions. Probiotics are nonpathogenic microorganisms able to interact with the gut microbiota and provide health benefits; their use has recently been exploited to dampen immunological response in several experimental models of autoimmune diseases. Here, we focus on the relationships among commensal bacteria, probiotics, and the gut, describing the main interactions occurring with the immune system and recent data supporting the clinical efficacy of probiotic administration in rheumatoid arthritis, multiple sclerosis, and myasthenia gravis (MG) animal models. The encouraging results suggest that selected strains of probiotics should be evaluated in clinical trials as adjuvant therapy to restore the disrupted tolerance in myasthenia gravis.

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Two rheumatoid arthritis–specific autoantigens correlate microbial immunity with autoimmune responses in joints

Cited by 183 publications

References 47 publications

Visions of Eye Commensals: The Known and the Unknown About How the Microbiome Affects Eye Disease

Visions of Eye Commensals: The Known and the Unknown About How the Microbiome Affects Eye Disease

Robust interferon signature and suppressed tissue repair gene expression in synovial tissue from patients with postinfectious,Borrelia burgdorferi‐induced Lyme arthritis

Gut microbiota and probiotics: novel immune system modulators in myasthenia gravis?

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