The Journal of rheumatology · 2026
Association of Type III and Type VI Collagen Neoepitopes With Disease Severity in Systemic Sclerosis.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Ayla Ali Y, Bernstein Elana J, Zhang Meng, VanBuren John M, Castelino Flavia V, Chung Lorinda, Evnin Luke, Frech Tracy M, Gordon Jessica K, Hant Faye N, Hummers Laura K, Khanna Dinesh, Lakin Kimberly S, Lebiedz-Odrobina Dorota, Luo Yiming, Makol Ashima, Mayes Maureen, McMahan Zsuzsanna H, Molitor Jerry A, Moore Duncan F, Richardson Carrie, Sandorfi Nora, Shah Ami A, Shah Ankoor, Shanmugam Victoria K, Skaug Brian, Steen Virginia D, Volkmann Elizabeth R, Zahn Carleigh, Zheng Wenjin J, Assassi Shervin
Аннотация
OBJECTIVE: Dysregulated collagen turnover is implicated in systemic sclerosis (SSc) pathogenesis. We evaluated collagen turnover biomarkers in relation to the severity of fibrotic manifestations, key cytokines, and progression in SSc.
METHODS: Baseline and 6-month serum samples of patients with early SSc in the Collaborative National Quality and Efficacy Registry (CONQUER) cohort were analyzed for type III (pro-collagen III [PRO-C3] and collagen III M [C3M]) and type VI (pro-collagen VI [PRO-C6] and collagen VI M [C6M]) collagen turnover biomarkers, as well as C-reactive protein (CRP), interleukin 6 (IL-6), and interferon (IFN)-inducible proteins. The modified Rodnan skin score and % predicted forced vital capacity (FVC%) served as surrogate markers of disease severity.
RESULTS: A total of 222 patients were included. PRO-C3 (P < 0.001) and PRO-C6 (P < 0.001) concentrations were higher in patients with diffuse disease, whereas C6M (P = 0.04) was higher in those with interstitial lung disease. Baseline PRO-C3 (P < 0.001) and PRO-C6 (P < 0.001) positively correlated with mRSS, whereas C3M (P = 0.03) and C6M (P = 0.01) negatively correlated with FVC%, although the magnitude of the observed correlations was in the weak range (rs < 0.4). Collagen biomarker concentrations positively correlated with CRP, IL-6, and IFN-inducible proteins at baseline. Although changes in CRP positively correlated with changes in collagen degradation protein levels (C3M and C6M), they did not correlate with changes in collagen formation protein levels (PRO-C3 and PRO-C6). In contrast, changes in IFN score showed the highest correlation with changes in PRO-C6.
CONCLUSION: PRO-C3 and PRO-C6 correlated with skin disease severity, whereas C3M and C6M correlated with lung disease severity. Collagen turnover biomarkers correlated with CRP, IL-6, and IFN-inducible proteins, providing support for the link between inflammation and fibrosis in SSc.
METHODS: Baseline and 6-month serum samples of patients with early SSc in the Collaborative National Quality and Efficacy Registry (CONQUER) cohort were analyzed for type III (pro-collagen III [PRO-C3] and collagen III M [C3M]) and type VI (pro-collagen VI [PRO-C6] and collagen VI M [C6M]) collagen turnover biomarkers, as well as C-reactive protein (CRP), interleukin 6 (IL-6), and interferon (IFN)-inducible proteins. The modified Rodnan skin score and % predicted forced vital capacity (FVC%) served as surrogate markers of disease severity.
RESULTS: A total of 222 patients were included. PRO-C3 (P < 0.001) and PRO-C6 (P < 0.001) concentrations were higher in patients with diffuse disease, whereas C6M (P = 0.04) was higher in those with interstitial lung disease. Baseline PRO-C3 (P < 0.001) and PRO-C6 (P < 0.001) positively correlated with mRSS, whereas C3M (P = 0.03) and C6M (P = 0.01) negatively correlated with FVC%, although the magnitude of the observed correlations was in the weak range (rs < 0.4). Collagen biomarker concentrations positively correlated with CRP, IL-6, and IFN-inducible proteins at baseline. Although changes in CRP positively correlated with changes in collagen degradation protein levels (C3M and C6M), they did not correlate with changes in collagen formation protein levels (PRO-C3 and PRO-C6). In contrast, changes in IFN score showed the highest correlation with changes in PRO-C6.
CONCLUSION: PRO-C3 and PRO-C6 correlated with skin disease severity, whereas C3M and C6M correlated with lung disease severity. Collagen turnover biomarkers correlated with CRP, IL-6, and IFN-inducible proteins, providing support for the link between inflammation and fibrosis in SSc.