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Abstract
Fibrosis across different organs and tissues is likely to share common pathophysiological mechanisms and pathways. Recently, a polymorphism (rs12979860) near the interferon lambda gene (IFNL3) was shown to be associated with fibrosis in liver across multiple disease etiologies. We determined whether this variant is a risk factor for pulmonary fibrosis (PF) and worsening cutaneous fibrosis in systemic sclerosis (SSc). Caucasian patients with SSc (n = 733) were genotyped to test for association with the presence of PF and worsening of skin fibrosis. Serum IFN-λ3 levels from 200 SSc cases were evaluated. An association of the IFNL3 polymorphism with PF was demonstrated (OR: 1.66 (95% CI: 1.142–2.416, p = 0.008). The IFNL3 variant was not a risk factor for worsening of skin fibrosis. Functionally, IFN-λ3 serum levels were higher among subjects with PF compared to those unaffected (P < 0.0001). In conclusion, IFNL3 serum levels and the genetic variant known to be associated with liver fibrosis are similarly linked to PF, but not to worsening of skin fibrosis in SSc. These data highlight both common fibrosis pathways operating between organs, as well as differential effects within the same disease.
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1 Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia
2 Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia; Department of Biochemistry, Faculty of Pharmacy, Minia University, Minia, Egypt
3 Department of Rheumatology St Vincent’s Hospital (Melbourne), 41 Victoria Parade, Fitzroy, Victoria, Australia; Department of Medicine, The University of Melbourne at St Vincent’s Hospital (Melbourne), 41 Victoria Parade, Fitzroy, Victoria, Australia
4 Department of Rheumatology St Vincent’s Hospital (Melbourne), 41 Victoria Parade, Fitzroy, Victoria, Australia
5 Department of Rheumatology, Monash Health, 246 Clayton Road, Clayton, Victoria, Australia; Department of Medicine, Monash University (Melbourne), Clayton, Victoria, Australia
6 Department of Rheumatology, The Menzies Research Institute of Tasmania, Private Bag 23, Tasmania, Australia
7 Department of Rheumatology, Fiona Stanley Hospital (Perth), Murdoch, Western Australia, Australia
8 Canberra Rheumatology, Canberra, ACT, Australia
9 Department of Rheumatology St Vincent’s Hospital (Melbourne), 41 Victoria Parade, Fitzroy, Victoria, Australia; Barwon Rheumatology Services, Victoria, Australia
10 Rheumatology Unit, The Queen Elizabeth Hospital (Adelaide), Woodville, SA, Australia; Discipline of Medicine, University of Adelaide (Adelaide), Adelaide, SA, Australia
11 Rheumatology Unit, Flinders Medical Centre (Adelaide), Flinders Drive, Bedford Park, South Australia, Australia; Rheumatology Unit, Royal Adelaide Hospital (Adelaide), Adelaide, SA, Australia; Immunology, Allergy and Arthritis Department, Flinders University (Adelaide), Bedford Park, South Australia, Australia
12 Departments of Clinical Immunology and Immunopathology, Royal Adelaide Hospital, Adelaide, Australia
13 Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
14 Rheumatology Department, The University of Sydney, Westmead Hospital, Westmead, NSW, Australia
15 Referral Center for Systemic Autoimmune Diseases, University of Milan and Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, via Pace 9, Milan, Italy
16 Rheumatology Unit, Royal Adelaide Hospital (Adelaide), Adelaide, SA, Australia; Discipline of Medicine, University of Adelaide (Adelaide), Adelaide, SA, Australia