Immunoscience, Nordic Bioscience, Herlev Hovedgade 205-207, 2730, Herlev, Denmark.
Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Sci Rep. 2023 Feb 21;13(1):3056. doi: 10.1038/s41598-023-28746-2.
Extracellular matrix (ECM) remodeling of the skin is a continuous process necessary for maintaining tissue homeostasis. Type VI collagen (COL6) is characterized as a beaded filament, located in the dermal ECM, where COL6-α6-chain has been demonstrated upregulated in atopic dermatitis. The aim of this study was to develop and validate a competitive ELISA, targeting the N-terminal of COL6-α6-chain, named C6A6, and evaluate its associations with the dermatological condition's atopic dermatitis, psoriasis, hidradenitis suppurativa, systemic lupus erythematosus, systemic sclerosis, urticaria, vitiligo, and cutaneous malignant melanoma in comparison, to healthy controls. A monoclonal antibody was raised and employed in an ELISA assay. The assay was developed, technically validated, and evaluated in two independent patient cohorts. Cohort 1 showed C6A6 was significantly elevated in patients with atopic dermatitis (p < 0.0001), psoriasis (p < 0.0001), hidradenitis suppurativa (p = 0.0095), systemic lupus erythematosus (p = 0.0032) and melanoma (p < 0.0001) compared to healthy donors. Cohort 2 confirmed C6A6 being upregulated in atopic dermatitis compared to healthy controls (p < 0.0001), but also associated with disease severity (SCORAD, p = 0.046) and lowered in patients receiving calcineurin inhibitors (p = 0.014). These findings are hypothesis generating, and the utility of the C6A6 biomarker for disease severity and treatment response needs to be validated in larger cohorts and longitudinal studies.
细胞外基质(ECM)的重塑是维持组织内稳态所必需的持续过程。VI 型胶原(COL6)的特征为珠状纤维,位于真皮 ECM 中,已证实 COL6-α6 链在特应性皮炎中上调。本研究旨在开发和验证针对 COL6-α6 链 N 端的竞争性 ELISA,命名为 C6A6,并评估其与特应性皮炎、银屑病、化脓性汗腺炎、系统性红斑狼疮、系统性硬皮病、荨麻疹、白癜风和皮肤恶性黑色素瘤等皮肤病况的相关性,与健康对照组进行比较。制备了单克隆抗体并用于 ELISA 检测。该检测方法在两个独立的患者队列中进行了开发、技术验证和评估。队列 1 显示,与健康供体相比,特应性皮炎(p<0.0001)、银屑病(p<0.0001)、化脓性汗腺炎(p=0.0095)、系统性红斑狼疮(p=0.0032)和黑色素瘤(p<0.0001)患者的 C6A6 显著升高。队列 2 证实,与健康对照组相比,C6A6 在特应性皮炎患者中上调(p<0.0001),但与疾病严重程度(SCORAD,p=0.046)相关,并且在接受钙调神经磷酸酶抑制剂治疗的患者中降低(p=0.014)。这些发现具有启发性,需要在更大的队列和纵向研究中验证 C6A6 生物标志物在疾病严重程度和治疗反应中的效用。