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.

Details

Title
IFNL3 genotype is associated with pulmonary fibrosis in patients with systemic sclerosis
Author
Metwally, Mayada 1 ; Thabet, Khaled 2 ; Bayoumi, Ali 1 ; Nikpour, Mandana 3 ; Stevens, Wendy 4 ; Sahhar, Joanne 5 ; Zochling, Jane 6 ; Roddy, Janet 7 ; Tymms, Kathleen 8 ; Strickland, Gemma 9 ; Lester, Susan 10 ; Rischmueller, Maureen 10 ; Gene-Siew Ngian 5 ; Walker, Jennifer 11 ; Hissaria, Pravin 12 ; Shaker, Olfat 13   VIAFID ORCID Logo  ; Liddle, Christopher 1   VIAFID ORCID Logo  ; Manolios, Nicholas 14 ; Beretta, Lorenzo 15 ; Proudman, Susanna 16 ; Jacob, George 1   VIAFID ORCID Logo  ; Mohammed Eslam 1 

 Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia 
 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 
 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 
 Department of Rheumatology St Vincent’s Hospital (Melbourne), 41 Victoria Parade, Fitzroy, Victoria, Australia 
 Department of Rheumatology, Monash Health, 246 Clayton Road, Clayton, Victoria, Australia; Department of Medicine, Monash University (Melbourne), Clayton, Victoria, Australia 
 Department of Rheumatology, The Menzies Research Institute of Tasmania, Private Bag 23, Tasmania, Australia 
 Department of Rheumatology, Fiona Stanley Hospital (Perth), Murdoch, Western Australia, Australia 
 Canberra Rheumatology, Canberra, ACT, Australia 
 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 
Pages
1-5
Publication year
2019
Publication date
Oct 2019
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2306200780
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.