Peripheral blood leucocyte telomere length is associated with progression of interstitial lung disease in systemic sclerosis.
connective tissue disease associated lung disease
interstitial fibrosis
rare lung diseases
systemic disease and lungs
Journal
Thorax
ISSN: 1468-3296
Titre abrégé: Thorax
Pays: England
ID NLM: 0417353
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
received:
31
07
2020
accepted:
10
06
2021
pubmed:
18
7
2021
medline:
3
2
2022
entrez:
17
7
2021
Statut:
ppublish
Résumé
Peripheral blood leucocyte telomere length (PBL-TL) is associated with outcomes in patients with idiopathic pulmonary fibrosis. Whether PBL-TL is associated with progression of systemic sclerosis-associated interstitial lung disease (SSc-ILD) is unknown. A retrospective observational cohort study was performed using prospectively collected data from 213 patients with SSc followed at the University of California San Francisco (UCSF) Scleroderma Center. PBL-TL was measured by quantitative PCR of DNA isolated from peripheral blood. Associations between PBL-TL and pulmonary function test trends in patients with SSc-ILD were assessed by longitudinal analysis using Generalised Linear Mixed Models. Findings were validated in a cohort of 61 patients with SSc-ILD enrolled in the Stanford University Scleroderma Center database. Patients with UCSF SSc with ILD were found to have shorter PBL-TL compared with those without ILD (6554±671 base pairs (bp) vs 6782±698 bp, p=0.01). Shorter PBL-TL was associated with the presence of ILD (adjusted OR 2.1 per 1000 bp TL decrease, 95% CI [1.25 to 3.70], p=0.006). PBL-TL was shorter in patients with SSc-ILD lacking SSc-specific autoantibodies compared with seropositive subjects (6237±647 bp vs 6651±653 bp, p=0.004). Shorter PBL-TL was associated with increased risk for lung function deterioration with an average of 67 mL greater loss in per year for every 1000 bp decrease in PBL-TL in the combined SSc-ILD cohorts (longitudinal analysis, adjusted model: 95% CI -104 mL to -33 mL, p<0.001). These findings suggest that telomere dysfunction may be associated with SSc-ILD progression and that PBL-TL measurement may be useful for stratifying risk for SSc-ILD progression.
Sections du résumé
BACKGROUND
Peripheral blood leucocyte telomere length (PBL-TL) is associated with outcomes in patients with idiopathic pulmonary fibrosis. Whether PBL-TL is associated with progression of systemic sclerosis-associated interstitial lung disease (SSc-ILD) is unknown.
METHODS
A retrospective observational cohort study was performed using prospectively collected data from 213 patients with SSc followed at the University of California San Francisco (UCSF) Scleroderma Center. PBL-TL was measured by quantitative PCR of DNA isolated from peripheral blood. Associations between PBL-TL and pulmonary function test trends in patients with SSc-ILD were assessed by longitudinal analysis using Generalised Linear Mixed Models. Findings were validated in a cohort of 61 patients with SSc-ILD enrolled in the Stanford University Scleroderma Center database.
RESULTS
Patients with UCSF SSc with ILD were found to have shorter PBL-TL compared with those without ILD (6554±671 base pairs (bp) vs 6782±698 bp, p=0.01). Shorter PBL-TL was associated with the presence of ILD (adjusted OR 2.1 per 1000 bp TL decrease, 95% CI [1.25 to 3.70], p=0.006). PBL-TL was shorter in patients with SSc-ILD lacking SSc-specific autoantibodies compared with seropositive subjects (6237±647 bp vs 6651±653 bp, p=0.004). Shorter PBL-TL was associated with increased risk for lung function deterioration with an average of 67 mL greater loss in per year for every 1000 bp decrease in PBL-TL in the combined SSc-ILD cohorts (longitudinal analysis, adjusted model: 95% CI -104 mL to -33 mL, p<0.001).
CONCLUSIONS
These findings suggest that telomere dysfunction may be associated with SSc-ILD progression and that PBL-TL measurement may be useful for stratifying risk for SSc-ILD progression.
Identifiants
pubmed: 34272332
pii: thoraxjnl-2020-215918
doi: 10.1136/thoraxjnl-2020-215918
pmc: PMC9262637
mid: NIHMS1809927
doi:
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1186-1192Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL139897
Pays : United States
Organisme : NIAMS NIH HHS
ID : T32 AR050942
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
Références
J Rheumatol. 2009 Apr;36(4):773-80
pubmed: 19286849
Lancet Respir Med. 2014 Jul;2(7):557-65
pubmed: 24948432
Lancet Respir Med. 2017 Aug;5(8):639-647
pubmed: 28648751
J Clin Invest. 2018 Dec 3;128(12):5222-5234
pubmed: 30179220
Arthritis Rheumatol. 2019 Jun;71(6):972-982
pubmed: 30624031
JCI Insight. 2016 Sep 8;1(14):e86704
pubmed: 27699234
Eur Respir J. 2020 Aug 27;56(2):
pubmed: 32341108
Eur Respir J. 2019 Apr 11;53(4):
pubmed: 30635297
Eur Respir J. 2020 May 14;55(5):
pubmed: 32079645
Chest. 2017 Nov;152(5):999-1007
pubmed: 28629914
Rheumatology (Oxford). 2006 Jul;45(7):815-8
pubmed: 16449367
Ann Rheum Dis. 2013 Nov;72(11):1747-55
pubmed: 24092682
Thorax. 2017 Nov;72(11):1052-1054
pubmed: 28446663
Curr Rheumatol Rep. 2013 Jan;15(1):297
pubmed: 23288576
Am J Respir Crit Care Med. 2019 Nov 1;200(9):1154-1163
pubmed: 31268371
J Rheumatol. 2013 Apr;40(4):435-46
pubmed: 23378460
J Immunol. 2012 Sep 1;189(5):2635-44
pubmed: 22826322
Arthritis Rheumatol. 2017 Aug;69(8):1670-1678
pubmed: 28426895
Chest. 2013 Aug;144(2):586-592
pubmed: 23392130
Semin Arthritis Rheum. 2007 Jun;36(6):392-6
pubmed: 17204309
Exp Ther Med. 2018 Dec;16(6):5305-5309
pubmed: 30542487
Nucleic Acids Res. 2002 May 15;30(10):e47
pubmed: 12000852
Rheum Dis Clin North Am. 2003 May;29(2):371-90
pubmed: 12841300
Lancet Respir Med. 2018 Feb;6(2):154-160
pubmed: 29413083
Cancer Res. 2013 May 1;73(9):2817-28
pubmed: 23610451
Eur Respir J. 2020 Jan 16;55(1):
pubmed: 31619475
Arthritis Rheum. 2005 Sep;52(9):2889-96
pubmed: 16142750
J Am Acad Dermatol. 1995 Dec;33(6):973-8
pubmed: 7490368
Arthritis Rheum. 2007 May;56(5):1685-93
pubmed: 17469163
Immunity. 2016 Oct 18;45(4):903-916
pubmed: 27742546
Am J Respir Crit Care Med. 2018 Sep 1;198(5):e44-e68
pubmed: 30168753
Ann Rheum Dis. 2019 Aug;78(8):1142-1144
pubmed: 30679155
Arthritis Rheumatol. 2014 Feb;66(2):418-27
pubmed: 24504814
Br J Rheumatol. 1996 Aug;35(8):732-7
pubmed: 8761184
J Rheumatol. 2009 May;36(5):976-83
pubmed: 19273457