血浆胶原新表位与 ACCESS 和 GRADS 肉样瘤病队列中的多器官疾病有关

IF 9 1区 医学 Q1 RESPIRATORY SYSTEM
Thorax Pub Date : 2024-08-07 DOI:10.1136/thorax-2023-221095
Jannie Marie Bülow Sand, Henrik Jessen, Diana Julie Leeming, Sheeline Yu, Chris J Lee, Buqu Hu, Ying Sun, Taylor Adams, Taylor Pivarnik, Angela Liu, Samuel Woo, John R McGovern, Vitória Fiorini, Tina Saber, Jean Paul Higuero-Sevilla, Mridu Gulati, Naftali Kaminski, William Damsky, Albert C Shaw, Subhasis Mohanty, Gillian Goobie, Yingze Zhang, Erica Lyndrup Herzog, Changwan Ryu
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Methods We employed plasma samples from patients with sarcoidosis enrolled in A Case Control Etiologic Study of Sarcoidosis (ACCESS) and Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS), and healthy control patients recruited from the Yale community. Plasma concentrations of type III and VI collagen degradation (C3M and C6M) and formation (PRO-C3 and PRO-C6) were quantified via neoepitope-specific competitive ELISA, and statistical associations were sought with clinical phenotypes. Results Relative to healthy controls, the plasma of both sarcoidosis cohorts was enriched for C3M and C6M, irrespective of corticosteroid use and disease duration. While circulating collagen neoepitopes were independent of Scadding stage, there was a significant association between multiorgan disease and PRO-C3, PRO-C6 and C3M in the ACCESS cohort; PRO-C3 and C6M displayed this property in GRADS. 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引用次数: 0

摘要

导言肉样瘤病的发病机制包括细胞外基质异常堆积引起的组织重塑,这部分是胶原合成、交联和降解失衡的结果。在这一过程中,胶原碎片或新表皮释放到血液循环中。这些循环中的胶原新表位在肉样瘤病中的意义尚不清楚。方法 我们采用了参加肉样瘤病病因病例对照研究(ACCESS)和α-1抗胰蛋白酶缺乏症与肉样瘤病基因组研究(GRADS)的肉样瘤病患者以及从耶鲁大学社区招募的健康对照组患者的血浆样本。通过新表皮特异性竞争性酶联免疫吸附法对血浆中Ⅲ型和Ⅵ型胶原降解(C3M和C6M)和形成(PRO-C3和PRO-C6)的浓度进行量化,并寻求与临床表型的统计学关联。结果 与健康对照组相比,两组肉样瘤病患者的血浆中都富含C3M和C6M,与皮质类固醇的使用和病程长短无关。虽然循环胶原新表位与斯卡丁分期无关,但在 ACCESS 队列中,多器官疾病与 PRO-C3、PRO-C6 和 C3M 之间存在显著关联;在 GRADS 中,PRO-C3 和 C6M 也显示出这种特性。这些发现与血浆中白细胞介素-4(IL-4)、IL-5、IL-6、IL-9、IL-10 和 IL-13 的水平无关。此外,PRO-C3 在两组人群中都与皮肤病有关。讨论 在两个特征明确的肉样瘤病队列中,我们发现血浆中富含胶原降解的新表位(C3M 和 C6M)。在多器官疾病中,循环中的 III 型新表位(PRO-C3)的形成可能与皮肤肉样瘤病有关。在这一领域的进一步研究有可能促进对这一复杂疾病的致病机制的新认识。如有合理要求,可提供相关数据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Plasma collagen neoepitopes are associated with multiorgan disease in the ACCESS and GRADS sarcoidosis cohorts
Introduction The pathogenesis of sarcoidosis involves tissue remodelling mediated by the accumulation of abnormal extracellular matrix, which is partly the result of an imbalance in collagen synthesis, cross-linking and degradation. During this process, collagen fragments or neoepitopes, are released into the circulation. The significance of these circulating collagen neoepitopes in sarcoidosis remains unknown. Methods We employed plasma samples from patients with sarcoidosis enrolled in A Case Control Etiologic Study of Sarcoidosis (ACCESS) and Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS), and healthy control patients recruited from the Yale community. Plasma concentrations of type III and VI collagen degradation (C3M and C6M) and formation (PRO-C3 and PRO-C6) were quantified via neoepitope-specific competitive ELISA, and statistical associations were sought with clinical phenotypes. Results Relative to healthy controls, the plasma of both sarcoidosis cohorts was enriched for C3M and C6M, irrespective of corticosteroid use and disease duration. While circulating collagen neoepitopes were independent of Scadding stage, there was a significant association between multiorgan disease and PRO-C3, PRO-C6 and C3M in the ACCESS cohort; PRO-C3 and C6M displayed this property in GRADS. These findings were unrelated to plasma levels of interleukin-4 (IL-4), IL-5, IL-6, IL-9, IL-10 and IL-13. Moreover, PRO-C3 was associated with dermatological disease in both cohorts. Discussion In two well-characterised sarcoidosis cohorts, we discovered that the plasma is enriched for neoepitopes of collagen degradation (C3M and C6M). In multiorgan disease, there was an association with circulating neoepitopes of type III formation (PRO-C3), perhaps mediated by dermatological sarcoidosis. Further investigation in this arena has the potential to foster new insights into the pathogenic mechanisms of this complex disease. Data are available upon reasonable request.
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来源期刊
Thorax
Thorax 医学-呼吸系统
CiteScore
16.10
自引率
2.00%
发文量
197
审稿时长
1 months
期刊介绍: Thorax stands as one of the premier respiratory medicine journals globally, featuring clinical and experimental research articles spanning respiratory medicine, pediatrics, immunology, pharmacology, pathology, and surgery. The journal's mission is to publish noteworthy advancements in scientific understanding that are poised to influence clinical practice significantly. This encompasses articles delving into basic and translational mechanisms applicable to clinical material, covering areas such as cell and molecular biology, genetics, epidemiology, and immunology.
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