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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血浆胶原新表位与 ACCESS 和 GRADS 结节病队列中的多器官疾病相关


简介 结节病的发病机制涉及异常细胞外基质积累介导的组织重塑，这部分是胶原蛋白合成、交联和降解不平衡的结果。在此过程中，胶原蛋白片段或新表位被释放到循环中。这些循环胶原新表位在结节病中的意义仍然未知。方法 我们使用了结节病病例对照病因学研究 （ACCESS） 和 Alpha-1 抗胰蛋白酶缺乏症和结节病基因组研究 （GRADS） 中入组的结节病患者的血浆样本，以及从耶鲁社区招募的健康对照患者。通过新表位特异性竞争性 ELISA 定量 III 型和 VI 型胶原降解 （C3M 和 C6M） 和形成 （PRO-C3 和 PRO-C6） 的血浆浓度，并寻求与临床表型的统计关联。结果 相对于健康对照，两个结节病队列的血浆中都富集了 C3M 和 C6M，与皮质类固醇的使用和病程无关。虽然循环胶原新表位与 Scadding 阶段无关，但在 ACCESS 队列中，多器官疾病与 PRO-C3 、 PRO-C6 和 C3M 之间存在显着关联;PRO-C3 和 C6M 在 GRADS 中显示此属性。这些发现与血浆白细胞介素 4 （IL-4） 、 IL-5 、 IL-6 、 IL-9 、 IL-10 和 IL-13 水平无关。此外，在两个队列中，PRO-C3 与皮肤病相关。讨论 在两个特征明确的结节病队列中，我们发现血浆富含胶原蛋白降解的新表位 （C3M 和 C6M）。 在多器官疾病中，与 III 型形成的循环新表位 （PRO-C3） 有关，可能是由皮肤结节病介导的。该领域的进一步研究有可能促进对这种复杂疾病的致病机制的新见解。数据可根据合理要求提供。