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

Mayada Metwally; Khaled Thabet; Ali Bayoumi; Mandana Nikpour; Wendy Stevens; Joanne Sahhar; Jane Zochling; Janet Roddy; Kathleen Tymms; Gemma Strickland; Susan Lester; Maureen Rischmueller; Gene Siew Ngian; Jennifer Walker; Pravin Hissaria; Olfat Shaker; Christopher Liddle; Nicholas Manolios; Lorenzo Beretta; Susanna Proudman; Jacob George; Mohammed Eslam

doi:10.1038/s41598-019-50709-9

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

Mayada Metwally, Khaled Thabet, Ali Bayoumi, Mandana Nikpour, Wendy Stevens, Joanne Sahhar, Jane Zochling, Janet Roddy, Kathleen Tymms, Gemma Strickland, Susan Lester, Maureen Rischmueller, Gene Siew Ngian, Jennifer Walker, Pravin Hissaria, Olfat Shaker, Christopher Liddle, Nicholas Manolios, Lorenzo Beretta, Susanna ProudmanJacob George^*, Mohammed Eslam

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

19 Citations (Scopus)

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.

Original language	English
Article number	14834
Journal	Scientific Reports
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41598-019-50709-9
Publication status	Published - 1 Dec 2019
Externally published	Yes

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Metwally, M., Thabet, K., Bayoumi, A., Nikpour, M., Stevens, W., Sahhar, J., Zochling, J., Roddy, J., Tymms, K., Strickland, G., Lester, S., Rischmueller, M., Ngian, G. S., Walker, J., Hissaria, P., Shaker, O., Liddle, C., Manolios, N., Beretta, L., ... Eslam, M. (2019). IFNL3 genotype is associated with pulmonary fibrosis in patients with systemic sclerosis. Scientific Reports, 9(1), Article 14834. https://doi.org/10.1038/s41598-019-50709-9

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title = "IFNL3 genotype is associated with pulmonary fibrosis in patients with systemic sclerosis",

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.",

author = "Mayada Metwally and Khaled Thabet and Ali Bayoumi and Mandana Nikpour and Wendy Stevens and Joanne Sahhar and Jane Zochling and Janet Roddy and Kathleen Tymms and Gemma Strickland and Susan Lester and Maureen Rischmueller and Ngian, {Gene Siew} and Jennifer Walker and Pravin Hissaria and Olfat Shaker and Christopher Liddle and Nicholas Manolios and Lorenzo Beretta and Susanna Proudman and Jacob George and Mohammed Eslam",

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = dec,

day = "1",

doi = "10.1038/s41598-019-50709-9",

language = "English",

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Metwally, M, Thabet, K, Bayoumi, A, Nikpour, M, Stevens, W, Sahhar, J, Zochling, J, Roddy, J, Tymms, K, Strickland, G, Lester, S, Rischmueller, M, Ngian, GS, Walker, J, Hissaria, P, Shaker, O, Liddle, C, Manolios, N, Beretta, L, Proudman, S, George, J & Eslam, M 2019, 'IFNL3 genotype is associated with pulmonary fibrosis in patients with systemic sclerosis', Scientific Reports, vol. 9, no. 1, 14834. https://doi.org/10.1038/s41598-019-50709-9

TY - JOUR

T1 - IFNL3 genotype is associated with pulmonary fibrosis in patients with systemic sclerosis

AU - Metwally, Mayada

AU - Thabet, Khaled

AU - Bayoumi, Ali

AU - Nikpour, Mandana

AU - Stevens, Wendy

AU - Sahhar, Joanne

AU - Zochling, Jane

AU - Roddy, Janet

AU - Tymms, Kathleen

AU - Strickland, Gemma

AU - Lester, Susan

AU - Rischmueller, Maureen

AU - Ngian, Gene Siew

AU - Walker, Jennifer

AU - Hissaria, Pravin

AU - Shaker, Olfat

AU - Liddle, Christopher

AU - Manolios, Nicholas

AU - Beretta, Lorenzo

AU - Proudman, Susanna

AU - George, Jacob

AU - Eslam, Mohammed

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85073450915&partnerID=8YFLogxK

U2 - 10.1038/s41598-019-50709-9

DO - 10.1038/s41598-019-50709-9

M3 - Article

SN - 2045-2322

VL - 9

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 14834

ER -

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

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