Type I interferon system activation and association with disease manifestations in systemic sclerosis

Eloranta, Maija‐Leena; Franck-Larsson, Karin; Lövgren, Tanja; Kalamajski, Sebastian; Rönnblom, Anders; Rubin, Kristofer; Alm, Gunnar V.; Rönnblom, Lars

doi:10.1136/ard.2009.121400

Cited by 159 publications

(149 citation statements)

References 32 publications

Supporting

Mentioning

133

Contrasting

Order By: Relevance

“…In the group of patients treated with active therapy, a greater deterioration of lung function and diffusing capacity for carbon monoxide was observed [28]. Later, it was suggested that IFN may be involved in the development of fibrosis or PAH in patients with scleroderma [29]. Similarly, it has been suggested that HIV infection could promote PAH through indirect mechanisms and release of inflammatory mediators or growth factors.…”

Section: Discussionmentioning

confidence: 99%

Pulmonary arterial hypertension in patients treated with interferon

et al. 2014

View full text Add to dashboard Cite

Isolated cases of pulmonary arterial hypertension (PAH) in patients treated with interferon (IFN) a or b have been reported in the literature.The aim of this study was to describe all consecutive cases of PAH patients with a history of IFN exposure identified in the French reference centre for severe pulmonary hypertension between 1998 and 2012.A total of 53 patients with PAH and a history of IFN therapy were identified. 48 patients had been treated with IFNa for chronic hepatitis C. Most of them had portal hypertension (85%) and 56% had HIV coinfection. Five additional patients had been treated with IFNb for multiple sclerosis. The diagnosis of PAH was made within 3 years after IFN therapy in 66% of patients. Repeated haemodynamic assessment was available in 13 out of 16 patients exposed to IFN after the diagnosis of PAH. Increased pulmonary vascular resistance .20% was observed in 11 out of 13 cases (median 43% increase; IQR 32-67%). In five of these patients, IFN withdrawal resulted in spontaneous haemodynamic improvement.This retrospective analysis suggests that IFN therapy may trigger PAH. However, most of these patients had other risk factors for PAH. A prospective case-control study is necessary to definitively establish a link between IFN exposure and PAH. @ERSpublications Clinical data suggest that interferon therapy may be a trigger for pulmonary arterial hypertension

show abstract

Section: Discussionmentioning

confidence: 99%

Pulmonary arterial hypertension in patients treated with interferon

et al. 2014

View full text Add to dashboard Cite

show abstract

“…The dysregulation of type I IFN signaling in SSc has been demonstrated by genetic linkage, as well as molecular and cellular data (Coelho et al, 2008;Eloranta et al, 2010;Carmona et al, 2013;Liu et al, 2013). Increased levels of IFN-inducible transcripts and chemokines have been associated with the more severe form of the disease (Eloranta et al, 2010;Higgs et al, 2011). IFN therapy has also been implicated in the development of SSc (Solans et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Suppression of T Cell Activation and Collagen Accumulation by an Anti-IFNAR1 mAb, Anifrolumab, in Adult Patients with Systemic Sclerosis

Guo

Higgs

Bay‐Jensen

et al. 2015

Journal of Investigative Dermatology

View full text Add to dashboard Cite

Type I IFNs are implicated in the pathophysiology of systemic sclerosis (SSc). Recently, a Phase I open-label trial was conducted with an anti-IFNAR1 receptor antibody (anifrolumab) in adult SSc patients. In this study, we aim to assess the downstream effects of anifrolumab and elucidate the role of type I IFN in SSc. Serum proteins and extracellular matrix (ECM) markers were measured in relation to IFN pathway activation status and SSc disease activity. Our results demonstrated a robust overexpression of multiple serum proteins in SSc patients, particularly those with an elevated baseline type I IFN gene signature. Anifrolumab administration was associated with significant downregulation of T cell-associated proteins and upregulation of type III collagen degradation marker. Whole-blood and skin microarray results also indicated the inhibition of T cell receptor and ECM-related transcripts by anifrolumab. In summary, our study demonstrates suppressive effects of anifrolumab on T cell activation and collagen accumulation through which tissue fibrosis may be reduced in SSc patients. The relationship between these peripheral markers and the clinical response to anifrolumab may be examined in larger double-blind, placebo-controlled trials.

show abstract

“…Case reports have documented incident systemic sclerosis arising in patients who had previously received IFNα therapy for chronic viral hepatitis [93,94]. An activated type I IFN profile and gene signature are present in patients with SSc and administration of MEDI-546 not only reduces serum levels of several IFN-induced proteins but also suppresses levels of markers of extracellular matrix turnover and TGF-β signalling [95,96].…”

Section: Type I Ifn Receptor Antagonistsmentioning

confidence: 99%

Translating Autoimmune Pathogenesis into Targeted Therapies for Systemic Sclerosis

Russell¹,

Sofat²

2017

Immunopathogenesis and Immune-Based Therapy for Selected Autoimmune Disorders

View full text Add to dashboard Cite

Targeted therapies including tumour necrosis factor α (TNFα) inhibitors have transformed the management of a number of autoimmune conditions over the past 20 years. One autoimmune rheumatological condition with significant potential for the development of targeted therapies is systemic sclerosis (SSc). In this chapter, we use SSc as an example of how research into the pathogenic processes underlying autoimmune conditions can be translated into novel targeted therapies. We review the evidence base for a range of targeted therapies for SSc identified from a systematic literature search, before highlighting a number of studies currently underway.

show abstract

Type I interferon system activation and association with disease manifestations in systemic sclerosis

Abstract: An activated type I IFN system previously seen in several other systemic autoimmune diseases is also present in SSc and may contribute to the vascular pathology and affect the profibrotic process.

Cited by 159 publications

References 32 publications

Pulmonary arterial hypertension in patients treated with interferon

Pulmonary arterial hypertension in patients treated with interferon

Suppression of T Cell Activation and Collagen Accumulation by an Anti-IFNAR1 mAb, Anifrolumab, in Adult Patients with Systemic Sclerosis

Translating Autoimmune Pathogenesis into Targeted Therapies for Systemic Sclerosis

Contact Info

Product

Resources

About