2. Academic Validation
  3. IFNL3 genotype is associated with pulmonary fibrosis in patients with systemic sclerosis

IFNL3 genotype is associated with pulmonary fibrosis in patients with systemic sclerosis

  • Sci Rep. 2019 Oct 16;9(1):14834. doi: 10.1038/s41598-019-50709-9.
Mayada Metwally 1,  Khaled Thabet 1 2,  Ali Bayoumi 1,  Mandana Nikpour 3 4,  Wendy Stevens 3,  Joanne Sahhar 5 6,  Jane Zochling 7,  Janet Roddy 8,  Kathleen Tymms 9,  Gemma Strickland 3 10,  Susan Lester 11 12,  Maureen Rischmueller 11 12,  Gene-Siew Ngian 5 6,  Jennifer Walker 13 14 15,  Pravin Hissaria 16,  Olfat Shaker 17,  Christopher Liddle 1,  Nicholas Manolios 18,  Lorenzo Beretta 19,  Susanna Proudman 14 12,  Jacob George 20,  Mohammed Eslam 21
Affiliations

Affiliations

  • 1 Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia.
  • 2 Department of Biochemistry, Faculty of Pharmacy, Minia University, Minia, Egypt.
  • 3 Department of Rheumatology St Vincent's Hospital (Melbourne), 41 Victoria Parade, Fitzroy, 3065, Victoria, Australia.
  • 4 Department of Medicine, The University of Melbourne at St Vincent's Hospital (Melbourne), 41 Victoria Parade, Fitzroy, 3065, Victoria, Australia.
  • 5 Department of Rheumatology, Monash Health, 246 Clayton Road, Clayton, Victoria, 3168, Australia.
  • 6 Department of Medicine, Monash University (Melbourne), Wellington Rd, Clayton, 3168, Victoria, Australia.
  • 7 Department of Rheumatology, The Menzies Research Institute of Tasmania, Private Bag 23, Tasmania, 7001, Australia.
  • 8 Department of Rheumatology, Fiona Stanley Hospital (Perth), 11 Robin Warren Drive, Murdoch, 6150, Western Australia, Australia.
  • 9 Canberra Rheumatology, Canberra, ACT, Australia.
  • 10 Barwon Rheumatology Services, Victoria, Australia.
  • 11 Rheumatology Unit, The Queen Elizabeth Hospital (Adelaide), 28 Woodville Rd, Woodville, 5011, SA, Australia.
  • 12 Discipline of Medicine, University of Adelaide (Adelaide), North Terrace, Adelaide, SA, 5000, Australia.
  • 13 Rheumatology Unit, Flinders Medical Centre (Adelaide), Flinders Drive, Bedford Park, 5042, South Australia, Australia.
  • 14 Rheumatology Unit, Royal Adelaide Hospital (Adelaide), Port Rd, Adelaide, SA, 5000, Australia.
  • 15 Immunology, Allergy and Arthritis Department, Flinders University (Adelaide), Sturt Road, Bedford Park, 5042, South Australia, Australia.
  • 16 Departments of Clinical Immunology and Immunopathology, Royal Adelaide Hospital, South Australia, Adelaide, Australia.
  • 17 Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
  • 18 Rheumatology Department, The University of Sydney, Westmead Hospital, Westmead, NSW, 2145, Australia.
  • 19 Referral Center for Systemic Autoimmune Diseases, University of Milan and Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, via Pace 9, I-20122, Milan, Italy.
  • 20 Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia. [email protected].
  • 21 Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia. [email protected].
PMID: 31619697 DOI: 10.1038/s41598-019-50709-9
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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