Absence of filarial infection in patients of systemic lupus erythematosus (SLE) in filarial endemic area: a possible protective role

Panda, Aditya K.; Das, B. K.

doi:10.1177/0961203314546019

Cited by 8 publications

(8 citation statements)

References 12 publications

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“…The Hygiene Hypothesis proposes that the recent, rapid eradication of parasitic worms and other pathogens occurring during urbanisation and industrialisation has resulted in populations exhibiting chronically unbalanced, hyperactive immune systems that likely contribute to the corresponding dramatically increased incidence of allergic, autoimmune and metabolic conditions worldwide 1 . Epidemiological evidence supports this hypothesis, most strikingly for autoimmunity in reports from India demonstrating clear evidence of an inverse relationship between infection with filarial nematodes and incidence of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) 2–4 . Together with data from a range of experimental animal models of chronic inflammatory diseases 1 , these findings underpin the recent interest in developing “helminth therapies” based on infections with worms or their immunomodulatory products that have evolved to promote their survival by acting to dampen host inflammation and pathology 1 .…”

Section: Introductionmentioning

confidence: 91%

ES-62 suppression of arthritis reflects epigenetic rewiring of synovial fibroblasts to a joint-protective phenotype

Corbet

Pineda

Yang

et al. 2020

Preprint

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The parasitic worm product, ES-62 protects against collagen-induced arthritis, a mouse model of rheumatoid arthritis (RA) by suppressing the synovial fibroblast (SF) responses perpetuating inflammation and driving joint destruction. Such SF responses are shaped during disease progression by the inflammatory microenvironment of the joint that promotes remodelling of their epigenetic landscape, inducing an “aggressive” pathogenic SF phenotype. Critically, exposure to ES-62 in vivo induces a stably imprinted “safe” phenotype that exhibits responses more typical of healthy SFs. Surprisingly however, DNA methylome analysis reveals that rather than simply preventing the pathogenic rewiring of SFs, ES-62 induces further epigenetic remodelling, including targeting genes associated with ciliogenesis and differentiation, to program a distinct “protective” phenotype. Such unique behaviour signposts potential DNA methylation signatures predictive of pathogenesis and its resolution and hence, candidate mechanisms by which novel therapeutic interventions could prevent SFs from perpetuating joint inflammation and destruction in RA.

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Section: Introductionmentioning

confidence: 91%

ES-62 suppression of arthritis reflects epigenetic rewiring of synovial fibroblasts to a joint-protective phenotype

Corbet

Pineda

Yang

et al. 2020

Preprint

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“…Whether the protection afforded by GI helminths against these disorders similarly involves interaction with the microbiome is not clear but infection with Heligmosomoides polygyrus and Trichuris muris can result in increases in Lactobacillaceae and decreases in Prevotella species 2,11,12 , commensals reported to be dysregulated in RA patients 9,10 . In any case, helminth-mediated protection against autoimmune disease is not limited to GI-tract parasites, with particularly striking examples of this involving filarial nematodes preventing development of RA 13 and SLE 14 . However, it is unclear whether tissue-resident or blood-borne parasitic worms can mediate these effects via modulation of the host microbiome and if so, which mechanisms they utilise.…”

Section: Introductionmentioning

confidence: 99%

The parasitic worm product ES-62 normalises the gut microbiota bone marrow axis in inflammatory arthritis

et al. 2019

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The human immune system has evolved in the context of our colonisation by bacteria, viruses, fungi and parasitic helminths. Reflecting this, the rapid eradication of pathogens appears to have resulted in reduced microbiome diversity and generation of chronically activated immune systems, presaging the recent rise of allergic, autoimmune and metabolic disorders. Certainly, gastrointestinal helminths can protect against gut and lung mucosa inflammatory conditions by modulating the microbiome and suppressing the chronic inflammation associated with dysbiosis. Here, we employ ES-62, an immunomodulator secreted by tissue-dwelling Acanthocheilonema viteae to show that helminth-modulation of the gut microbiome does not require live infection with gastrointestinal-based worms nor is protection restricted to mucosal diseases. Specifically, subcutaneous administration of this defined immunomodulator affords protection against joint disease in collagen-induced arthritis, a mouse model of rheumatoid arthritis, which is associated with normalisation of gut microbiota and prevention of loss of intestinal barrier integrity.

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“…Extensive studies (reviewed [8][9][10]) have strongly evidenced the potential of worm therapy in animal models and although less consistent, particularly with respect to allergic responses, this has been supported by epidemiological data from endemic regions. Indeed, there are striking inverse incidences between infection with filarial nematode worms and both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) [11][12][13], as well as a lower prevalence of filarial infection in type 2 diabetes patients, in India.…”

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confidence: 99%

Can Parasitic Worms Cure the Modern World’s Ills?

Harnett

2017

Trends in Parasitology

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There has been increasing recognition that the alarming surge in allergy and autoimmunity in the industrialised and developing worlds shadows the rapid eradication of pathogens, such as parasitic helminths. Appreciation of this has fuelled an explosion in research investigating the therapeutic potential of these worms. This review considers the current state-of-play with a particular focus on exciting recent advances in the identification of potential novel targets for immunomodulation that can be exploited therapeutically. Furthermore, we contemplate the prospects for designing worm-derived immunotherapies for an ever-widening range of inflammatory diseases, including, for example, obesity, cardiovascular disease, and ageing as well as neurodevelopmental disorders like autism.

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Absence of filarial infection in patients of systemic lupus erythematosus (SLE) in filarial endemic area: a possible protective role

Cited by 8 publications

References 12 publications

ES-62 suppression of arthritis reflects epigenetic rewiring of synovial fibroblasts to a joint-protective phenotype

ES-62 suppression of arthritis reflects epigenetic rewiring of synovial fibroblasts to a joint-protective phenotype

The parasitic worm product ES-62 normalises the gut microbiota bone marrow axis in inflammatory arthritis

Can Parasitic Worms Cure the Modern World’s Ills?

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