eprintid: 10118088 rev_number: 25 eprint_status: archive userid: 608 dir: disk0/10/11/80/88 datestamp: 2021-01-07 11:13:44 lastmod: 2022-02-25 16:35:01 status_changed: 2021-01-07 11:13:44 type: article metadata_visibility: show creators_name: Stock, CJW creators_name: Hoyles, RK creators_name: Daccord, C creators_name: Kokosi, M creators_name: Visca, D creators_name: De Lauretis, A creators_name: Alfieri, V creators_name: Kouranos, V creators_name: Margaritopoulos, G creators_name: George, PM creators_name: Molyneaux, PL creators_name: Chua, F creators_name: Maher, TM creators_name: Abraham, DJ creators_name: Ong, V creators_name: Donovan, J creators_name: Sestini, P creators_name: Denton, CP creators_name: Wells, AU creators_name: Renzoni, EA title: Serum markers of pulmonary epithelial damage in systemic sclerosis-associated interstitial lung disease and disease progression ispublished: pub divisions: UCL divisions: B02 divisions: C10 divisions: D17 divisions: G90 keywords: CYFRA 21-1, Krebs von den Lungen-6, MUC1 allele, biomarker, disease progression, systemic sclerosis-associated interstitial lung disease note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. abstract: BACKGROUND AND OBJECTIVE: The course of systemic sclerosis-associated interstitial lung disease (SSc-ILD) is highly variable, and accurate prognostic markers are needed. KL-6 is a mucin-like glycoprotein (MUC1) expressed by type II pneumocytes, while CYFRA 21-1 is expressed by alveolar and bronchiolar epithelial cells. Both are released into the blood from cell injury. METHODS: Serum KL-6 and CYFRA 21-1 levels were measured in a retrospective (n = 189) and a prospective (n = 118) cohort of SSc patients. Genotyping of MUC1 rs4072037 was performed. Linear mixed-effect models were used to evaluate the relationship with change in lung function parameters over time, while association with survival was evaluated with Cox proportional hazard analysis. RESULTS: In both cohorts, KL-6 and CYFRA 21-1 were highest in patients with lung involvement, and in patients with extensive rather than limited ILD. KL-6 was higher in patients carrying the MUC1 rs4072037 G allele in both cohorts. In patients with SSc-ILD, serum KL-6, but not CYFRA 21-1, was significantly associated with DLCO decline in both cohorts (P = 0.001 and P = 0.004, respectively), and with FVC decline in the retrospective cohort (P = 0.005), but not the prospective cohort. When combining the cohorts and subgrouping by severity (median CPI = 45.97), KL-6 remained predictive of decline in DLCO in both milder (P = 0.007) and more severe disease (P = 0.02) on multivariable analysis correcting for age, gender, ethnicity, smoking history and MUC1 allele carriage. CONCLUSION: Our results suggest serum KL-6 predicts decline in lung function in SSc, suggesting its clinical utility in risk stratification for progressive SSc-ILD. date: 2021-05 date_type: published official_url: http://dx.doi.org/10.1111/resp.13988 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1839436 doi: 10.1111/resp.13988 lyricists_name: Abraham, David lyricists_name: Denton, Christopher lyricists_name: Ong, Voon lyricists_id: DJABR26 lyricists_id: CPDEN87 lyricists_id: VONGX45 actors_name: Denton, Christopher actors_id: CPDEN87 actors_role: owner full_text_status: public publication: Respirology volume: 26 number: 5 pagerange: 461-468 event_location: Australia citation: Stock, CJW; Hoyles, RK; Daccord, C; Kokosi, M; Visca, D; De Lauretis, A; Alfieri, V; ... Renzoni, EA; + view all <#> Stock, CJW; Hoyles, RK; Daccord, C; Kokosi, M; Visca, D; De Lauretis, A; Alfieri, V; Kouranos, V; Margaritopoulos, G; George, PM; Molyneaux, PL; Chua, F; Maher, TM; Abraham, DJ; Ong, V; Donovan, J; Sestini, P; Denton, CP; Wells, AU; Renzoni, EA; - view fewer <#> (2021) Serum markers of pulmonary epithelial damage in systemic sclerosis-associated interstitial lung disease and disease progression. Respirology , 26 (5) pp. 461-468. 10.1111/resp.13988 <https://doi.org/10.1111/resp.13988>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10118088/7/Abraham_Respirology%20-%202020%20-%20Stock%20-%20Serum%20markers%20of%20pulmonary%20epithelial%20damage%20in%20systemic%20sclerosis%E2%80%90associated%20interstitial.pdf