MUC5B promoter variant rs35705950 and rheumatoid arthritis associated interstitial lung disease survival and progression

Pierre Antoine Juge; Joshua J. Solomon; Coline H.M. van Moorsel; Romain Garofoli; Joyce S. Lee; Fabienne Louis-Sydney; Jorge Rojas-Serrano; Montserrat I. González-Pérez; Mayra Mejia; Ivette Buendia-Roldán; Ramcés Falfán-Valencia; Enrique Ambrocio-Ortiz; Effrosyni Manali; Spyros A. Papiris; Theofanis Karageorgas; Dimitrios Boumpas; Katarina M. Antoniou; Prodromos Sidiropoulos; Athina Trachalaki; Joanne J. van der Vis; Anna Jamnitski; Jan C. Grutters; Caroline Kannengiesser; Raphaël Borie; Leticia Kawano-Dourado; Lidwine Wemeau-Stervinou; René Marc Flipo; Hilario Nunes; Yurdagul Uzunhan; Dominique Valeyre; Nathalie Saidenberg-Kermanac'h; Marie Christophe Boissier; Christophe Richez; Thierry Schaeverbeke; Tracy Doyle; Paul J. Wolters; Marie Pierre Debray; Catherine Boileau; Raphaël Porcher; David A. Schwartz; Bruno Crestani; Philippe Dieudé

doi:10.1016/j.semarthrit.2021.07.002

MUC5B promoter variant rs35705950 and rheumatoid arthritis associated interstitial lung disease survival and progression

Pierre Antoine Juge
, Joshua J. Solomon
, Coline H.M. van Moorsel
, Romain Garofoli
, Joyce S. Lee
, Fabienne Louis-Sydney
, Jorge Rojas-Serrano
, Montserrat I. González-Pérez
, Mayra Mejia
, Ivette Buendia-Roldán
, Ramcés Falfán-Valencia
, Enrique Ambrocio-Ortiz
, Effrosyni Manali
, Spyros A. Papiris
, Theofanis Karageorgas
, Dimitrios Boumpas
, Katarina M. Antoniou
, Prodromos Sidiropoulos
, Athina Trachalaki
, Joanne J. van der Vis

Anna Jamnitski, Jan C. Grutters, Caroline Kannengiesser, Raphaël Borie, Leticia Kawano-Dourado, Lidwine Wemeau-Stervinou, René Marc Flipo, Hilario Nunes, Yurdagul Uzunhan, Dominique Valeyre, Nathalie Saidenberg-Kermanac'h, Marie Christophe Boissier, Christophe Richez, Thierry Schaeverbeke, Tracy Doyle, Paul J. Wolters, Marie Pierre Debray, Catherine Boileau, Raphaël Porcher, David A. Schwartz, Bruno Crestani, Philippe Dieudé^*

^*Corresponding author for this work

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

Abstract

Background: The major risk factor for idiopathic pulmonary fibrosis (IPF), MUC5B rs35705950, was found to be associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Whilst the MUC5B rs35705950 T risk allele has been associated with better survival in IPF, its impact on RA-ILD prognosis remains to be determined. Our objective was to explore the influence of MUC5B rs35705950 on survival and progression in RA-ILD. Methods: Through an international retrospective observational study, patients with RA-ILD were genotyped for the MUC5B rs35705950 variant and consecutive pulmonary function tests (PFTs) findings were collected. Longitudinal data up to a 10-year follow-up were considered and analyzed using mixed regression models. Proportional hazards and joint proportional hazards models were used to analyze the association of baseline and longitudinal variables with lung transplant-free survival. Significant progression of RA-ILD was defined as at least an absolute or relative 10% decline of forced vital capacity at 2 years from baseline. Results: Out of 321 registered patients, 261 were included in the study: 139 women (53.3%), median age at RA-ILD diagnosis 65 years (interquartile range [IQR] 57 to 71), 151 ever smokers (59.2%). Median follow-up was 3.5 years (IQR 1.3 to 6.6). Mortality rate was 32% (95%CI 19 to 42) at 10 years. The MUC5B rs35705950 variant did not impact lung transplant-free survival (HR for the T risk allele carriers=1.26; 95%CI 0.61 to 2.62; P=0.53). Decline in pulmonary function at 2 years was not influenced by MUC5B rs35705950 (OR=0.95; 95%CI 0.44 to 2.05; P=0.89), irrespective of the HRCT pattern. Conclusion: In this study, the MUC5B rs35705950 promoter variant did not influence transplant- free survival or decline in pulmonary function in patients with RA-ILD.

Original language	English
Pages (from-to)	996-1004
Number of pages	9
Journal	Seminars in Arthritis and Rheumatism
Volume	51
Issue number	5
DOIs	https://doi.org/10.1016/j.semarthrit.2021.07.002
Publication status	Published - Oct 2021
Externally published	Yes

Keywords

Genetics
Interstitial Lung Disease
MUC5B
Rheumatoid Arthritis

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10.1016/j.semarthrit.2021.07.002

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Juge, P. A., Solomon, J. J., van Moorsel, C. H. M., Garofoli, R., Lee, J. S., Louis-Sydney, F., Rojas-Serrano, J., González-Pérez, M. I., Mejia, M., Buendia-Roldán, I., Falfán-Valencia, R., Ambrocio-Ortiz, E., Manali, E., Papiris, S. A., Karageorgas, T., Boumpas, D., Antoniou, K. M., Sidiropoulos, P., Trachalaki, A., ... Dieudé, P. (2021). MUC5B promoter variant rs35705950 and rheumatoid arthritis associated interstitial lung disease survival and progression. Seminars in Arthritis and Rheumatism, 51(5), 996-1004. https://doi.org/10.1016/j.semarthrit.2021.07.002

@article{8a3db05f5a2840939ac6355463924641,

title = "MUC5B promoter variant rs35705950 and rheumatoid arthritis associated interstitial lung disease survival and progression",

abstract = "Background: The major risk factor for idiopathic pulmonary fibrosis (IPF), MUC5B rs35705950, was found to be associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Whilst the MUC5B rs35705950 T risk allele has been associated with better survival in IPF, its impact on RA-ILD prognosis remains to be determined. Our objective was to explore the influence of MUC5B rs35705950 on survival and progression in RA-ILD. Methods: Through an international retrospective observational study, patients with RA-ILD were genotyped for the MUC5B rs35705950 variant and consecutive pulmonary function tests (PFTs) findings were collected. Longitudinal data up to a 10-year follow-up were considered and analyzed using mixed regression models. Proportional hazards and joint proportional hazards models were used to analyze the association of baseline and longitudinal variables with lung transplant-free survival. Significant progression of RA-ILD was defined as at least an absolute or relative 10\% decline of forced vital capacity at 2 years from baseline. Results: Out of 321 registered patients, 261 were included in the study: 139 women (53.3\%), median age at RA-ILD diagnosis 65 years (interquartile range [IQR] 57 to 71), 151 ever smokers (59.2\%). Median follow-up was 3.5 years (IQR 1.3 to 6.6). Mortality rate was 32\% (95\%CI 19 to 42) at 10 years. The MUC5B rs35705950 variant did not impact lung transplant-free survival (HR for the T risk allele carriers=1.26; 95\%CI 0.61 to 2.62; P=0.53). Decline in pulmonary function at 2 years was not influenced by MUC5B rs35705950 (OR=0.95; 95\%CI 0.44 to 2.05; P=0.89), irrespective of the HRCT pattern. Conclusion: In this study, the MUC5B rs35705950 promoter variant did not influence transplant- free survival or decline in pulmonary function in patients with RA-ILD.",

keywords = "Genetics, Interstitial Lung Disease, MUC5B, Rheumatoid Arthritis",

author = "Juge, \{Pierre Antoine\} and Solomon, \{Joshua J.\} and \{van Moorsel\}, \{Coline H.M.\} and Romain Garofoli and Lee, \{Joyce S.\} and Fabienne Louis-Sydney and Jorge Rojas-Serrano and Gonz{\'a}lez-P{\'e}rez, \{Montserrat I.\} and Mayra Mejia and Ivette Buendia-Rold{\'a}n and Ramc{\'e}s Falf{\'a}n-Valencia and Enrique Ambrocio-Ortiz and Effrosyni Manali and Papiris, \{Spyros A.\} and Theofanis Karageorgas and Dimitrios Boumpas and Antoniou, \{Katarina M.\} and Prodromos Sidiropoulos and Athina Trachalaki and \{van der Vis\}, \{Joanne J.\} and Anna Jamnitski and Grutters, \{Jan C.\} and Caroline Kannengiesser and Rapha{\"e}l Borie and Leticia Kawano-Dourado and Lidwine Wemeau-Stervinou and Flipo, \{Ren{\'e} Marc\} and Hilario Nunes and Yurdagul Uzunhan and Dominique Valeyre and Nathalie Saidenberg-Kermanac'h and Boissier, \{Marie Christophe\} and Christophe Richez and Thierry Schaeverbeke and Tracy Doyle and Wolters, \{Paul J.\} and Debray, \{Marie Pierre\} and Catherine Boileau and Rapha{\"e}l Porcher and Schwartz, \{David A.\} and Bruno Crestani and Philippe Dieud{\'e}",

note = "Funding Information: PAJ reports personal fees from BMS, outside the submitted work. JSL reports grants from NIH, personal fees from Genentech, personal fees from Celgene outside the submitted work. RB reports grants and personal fees from Roche, grants and personal fees from Boerhinger Ingelheim, outside the submitted work. LWS reports personal fees and non-financial support from Roche, personal fees and non-financial support from Boehringer-Ingelheim, personal fees from Janssen-Cilag, personal fees from Bristol-Myers-Squibb, outside the submitted work. RMF reports grants and personal fees from Roche Chugai, grants and personal fees from Abbvie, personal fees from Bristol-Meyers Squibb, grants and personal fees from Pfizer, outside the submitted work. YU reports personal fees from Roche, personal fees from Bohringer Ingelheim, non-financial support from Oxyvie, outside the submitted work. DV reports personal fees from Roche, personal fees from Bohringer Ingelheim, personal fees from Astra Zenecca, outside the submitted work. PJW reports grants from Genentech, grants from Medimmune, outside the submitted work. DAS reports grants from NIH-NHLBI, grants from NIH-NHLBI, grants from NIH-NHLBI, grants from NIH-NHLBI, grants from DOD Focused Program Grant, during the conduct of the study; other from Eleven P15, Inc., personal fees from NuMedii, Inc., outside the submitted work. In addition, DAS has a patent Compositions and Methods of Treating or Preventing Fibrotic Diseases pending, a patent Biomarkers for the diagnosis and treatment of fibrotic lung disease pending, and a patent Methods and Compositions for Risk Prediction, Diagnosis, Prognosis, and Treatment of Pulmonary Disorders issued. BC reports grants from Apellis, grants and personal fees from Boehringer Ingelheim, personal fees from Astra Zeneca, grants from MedImmune, grants and personal fees from Roche, personal fees from Sanofi, outside the submitted work. PD reports grants from PFIZER, grants and personal fees from ROCHE, grants and personal fees from CHUGAI, grants and personal fees from BMS, personal fees from ABBVIE, personal fees from MSD, outside the submitted work. JS, CvM, RG, FLS, JRS, MIGP, MM, IBR, RFV, EAO, EM, SAP, TK, DB, KMA, PS, AT, JJvdV, AJ, JG, CK, HN, NSK, MCB, CR, TS, TD, MPD, CB and RP have nothing to disclose. Publisher Copyright: {\textcopyright} 2021",

year = "2021",

month = oct,

doi = "10.1016/j.semarthrit.2021.07.002",

language = "English",

volume = "51",

pages = "996--1004",

journal = "Seminars in Arthritis and Rheumatism",

issn = "0049-0172",

publisher = "W.B. Saunders",

number = "5",

}

Juge, PA, Solomon, JJ, van Moorsel, CHM, Garofoli, R, Lee, JS, Louis-Sydney, F, Rojas-Serrano, J, González-Pérez, MI, Mejia, M, Buendia-Roldán, I, Falfán-Valencia, R, Ambrocio-Ortiz, E, Manali, E, Papiris, SA, Karageorgas, T, Boumpas, D, Antoniou, KM, Sidiropoulos, P, Trachalaki, A, van der Vis, JJ, Jamnitski, A, Grutters, JC, Kannengiesser, C, Borie, R, Kawano-Dourado, L, Wemeau-Stervinou, L, Flipo, RM, Nunes, H, Uzunhan, Y, Valeyre, D, Saidenberg-Kermanac'h, N, Boissier, MC, Richez, C, Schaeverbeke, T, Doyle, T, Wolters, PJ, Debray, MP, Boileau, C, Porcher, R, Schwartz, DA, Crestani, B & Dieudé, P 2021, 'MUC5B promoter variant rs35705950 and rheumatoid arthritis associated interstitial lung disease survival and progression', Seminars in Arthritis and Rheumatism, vol. 51, no. 5, pp. 996-1004. https://doi.org/10.1016/j.semarthrit.2021.07.002

TY - JOUR

T1 - MUC5B promoter variant rs35705950 and rheumatoid arthritis associated interstitial lung disease survival and progression

AU - Juge, Pierre Antoine

AU - Solomon, Joshua J.

AU - van Moorsel, Coline H.M.

AU - Garofoli, Romain

AU - Lee, Joyce S.

AU - Louis-Sydney, Fabienne

AU - Rojas-Serrano, Jorge

AU - González-Pérez, Montserrat I.

AU - Mejia, Mayra

AU - Buendia-Roldán, Ivette

AU - Falfán-Valencia, Ramcés

AU - Ambrocio-Ortiz, Enrique

AU - Manali, Effrosyni

AU - Papiris, Spyros A.

AU - Karageorgas, Theofanis

AU - Boumpas, Dimitrios

AU - Antoniou, Katarina M.

AU - Sidiropoulos, Prodromos

AU - Trachalaki, Athina

AU - van der Vis, Joanne J.

AU - Jamnitski, Anna

AU - Grutters, Jan C.

AU - Kannengiesser, Caroline

AU - Borie, Raphaël

AU - Kawano-Dourado, Leticia

AU - Wemeau-Stervinou, Lidwine

AU - Flipo, René Marc

AU - Nunes, Hilario

AU - Uzunhan, Yurdagul

AU - Valeyre, Dominique

AU - Saidenberg-Kermanac'h, Nathalie

AU - Boissier, Marie Christophe

AU - Richez, Christophe

AU - Schaeverbeke, Thierry

AU - Doyle, Tracy

AU - Wolters, Paul J.

AU - Debray, Marie Pierre

AU - Boileau, Catherine

AU - Porcher, Raphaël

AU - Schwartz, David A.

AU - Crestani, Bruno

AU - Dieudé, Philippe

N1 - Funding Information: PAJ reports personal fees from BMS, outside the submitted work. JSL reports grants from NIH, personal fees from Genentech, personal fees from Celgene outside the submitted work. RB reports grants and personal fees from Roche, grants and personal fees from Boerhinger Ingelheim, outside the submitted work. LWS reports personal fees and non-financial support from Roche, personal fees and non-financial support from Boehringer-Ingelheim, personal fees from Janssen-Cilag, personal fees from Bristol-Myers-Squibb, outside the submitted work. RMF reports grants and personal fees from Roche Chugai, grants and personal fees from Abbvie, personal fees from Bristol-Meyers Squibb, grants and personal fees from Pfizer, outside the submitted work. YU reports personal fees from Roche, personal fees from Bohringer Ingelheim, non-financial support from Oxyvie, outside the submitted work. DV reports personal fees from Roche, personal fees from Bohringer Ingelheim, personal fees from Astra Zenecca, outside the submitted work. PJW reports grants from Genentech, grants from Medimmune, outside the submitted work. DAS reports grants from NIH-NHLBI, grants from NIH-NHLBI, grants from NIH-NHLBI, grants from NIH-NHLBI, grants from DOD Focused Program Grant, during the conduct of the study; other from Eleven P15, Inc., personal fees from NuMedii, Inc., outside the submitted work. In addition, DAS has a patent Compositions and Methods of Treating or Preventing Fibrotic Diseases pending, a patent Biomarkers for the diagnosis and treatment of fibrotic lung disease pending, and a patent Methods and Compositions for Risk Prediction, Diagnosis, Prognosis, and Treatment of Pulmonary Disorders issued. BC reports grants from Apellis, grants and personal fees from Boehringer Ingelheim, personal fees from Astra Zeneca, grants from MedImmune, grants and personal fees from Roche, personal fees from Sanofi, outside the submitted work. PD reports grants from PFIZER, grants and personal fees from ROCHE, grants and personal fees from CHUGAI, grants and personal fees from BMS, personal fees from ABBVIE, personal fees from MSD, outside the submitted work. JS, CvM, RG, FLS, JRS, MIGP, MM, IBR, RFV, EAO, EM, SAP, TK, DB, KMA, PS, AT, JJvdV, AJ, JG, CK, HN, NSK, MCB, CR, TS, TD, MPD, CB and RP have nothing to disclose. Publisher Copyright: © 2021

PY - 2021/10

Y1 - 2021/10

N2 - Background: The major risk factor for idiopathic pulmonary fibrosis (IPF), MUC5B rs35705950, was found to be associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Whilst the MUC5B rs35705950 T risk allele has been associated with better survival in IPF, its impact on RA-ILD prognosis remains to be determined. Our objective was to explore the influence of MUC5B rs35705950 on survival and progression in RA-ILD. Methods: Through an international retrospective observational study, patients with RA-ILD were genotyped for the MUC5B rs35705950 variant and consecutive pulmonary function tests (PFTs) findings were collected. Longitudinal data up to a 10-year follow-up were considered and analyzed using mixed regression models. Proportional hazards and joint proportional hazards models were used to analyze the association of baseline and longitudinal variables with lung transplant-free survival. Significant progression of RA-ILD was defined as at least an absolute or relative 10% decline of forced vital capacity at 2 years from baseline. Results: Out of 321 registered patients, 261 were included in the study: 139 women (53.3%), median age at RA-ILD diagnosis 65 years (interquartile range [IQR] 57 to 71), 151 ever smokers (59.2%). Median follow-up was 3.5 years (IQR 1.3 to 6.6). Mortality rate was 32% (95%CI 19 to 42) at 10 years. The MUC5B rs35705950 variant did not impact lung transplant-free survival (HR for the T risk allele carriers=1.26; 95%CI 0.61 to 2.62; P=0.53). Decline in pulmonary function at 2 years was not influenced by MUC5B rs35705950 (OR=0.95; 95%CI 0.44 to 2.05; P=0.89), irrespective of the HRCT pattern. Conclusion: In this study, the MUC5B rs35705950 promoter variant did not influence transplant- free survival or decline in pulmonary function in patients with RA-ILD.

AB - Background: The major risk factor for idiopathic pulmonary fibrosis (IPF), MUC5B rs35705950, was found to be associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Whilst the MUC5B rs35705950 T risk allele has been associated with better survival in IPF, its impact on RA-ILD prognosis remains to be determined. Our objective was to explore the influence of MUC5B rs35705950 on survival and progression in RA-ILD. Methods: Through an international retrospective observational study, patients with RA-ILD were genotyped for the MUC5B rs35705950 variant and consecutive pulmonary function tests (PFTs) findings were collected. Longitudinal data up to a 10-year follow-up were considered and analyzed using mixed regression models. Proportional hazards and joint proportional hazards models were used to analyze the association of baseline and longitudinal variables with lung transplant-free survival. Significant progression of RA-ILD was defined as at least an absolute or relative 10% decline of forced vital capacity at 2 years from baseline. Results: Out of 321 registered patients, 261 were included in the study: 139 women (53.3%), median age at RA-ILD diagnosis 65 years (interquartile range [IQR] 57 to 71), 151 ever smokers (59.2%). Median follow-up was 3.5 years (IQR 1.3 to 6.6). Mortality rate was 32% (95%CI 19 to 42) at 10 years. The MUC5B rs35705950 variant did not impact lung transplant-free survival (HR for the T risk allele carriers=1.26; 95%CI 0.61 to 2.62; P=0.53). Decline in pulmonary function at 2 years was not influenced by MUC5B rs35705950 (OR=0.95; 95%CI 0.44 to 2.05; P=0.89), irrespective of the HRCT pattern. Conclusion: In this study, the MUC5B rs35705950 promoter variant did not influence transplant- free survival or decline in pulmonary function in patients with RA-ILD.

KW - Genetics

KW - Interstitial Lung Disease

KW - MUC5B

KW - Rheumatoid Arthritis

UR - https://www.scopus.com/pages/publications/85112542342

U2 - 10.1016/j.semarthrit.2021.07.002

DO - 10.1016/j.semarthrit.2021.07.002

M3 - Article

C2 - 34411838

AN - SCOPUS:85112542342

SN - 0049-0172

VL - 51

SP - 996

EP - 1004

JO - Seminars in Arthritis and Rheumatism

JF - Seminars in Arthritis and Rheumatism

IS - 5

ER -

MUC5B promoter variant rs35705950 and rheumatoid arthritis associated interstitial lung disease survival and progression

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