Background/Purpose: Collagens are the main constituents of the skin. Genetic mutations in type VI, VII, and XVII collagen cause skin diseases, such as atopic dermatitis, epidermolysis bullosa, and bullous pemphigoid. These are all characterized as systemic diseases, with local manifestations. Novel collagen biomarkers hold the potential to detect skin manifestations, monitor the disease course, as well as improve our understanding of the pathophysiology. The objective of this study was to develop blood-based biomarkers of type VI, VII, and XVII collagen, and investigate their diagnostic potential for skin pathologies, including systemic sclerosis.

Methods: Three novel immunoassays targeting the N-terminal of type VI collagen (C6A6), an MMP-generated neo-epitope fragment of type VII collagen (C7M), and type XVII collagen (PRO-C17) were developed and used to measure the aforementioned analyte levels in serum from healthy donors (n=25), patients with atopic dermatitis (n=20) and systemic sclerosis (n=5).
Differences between biomarker levels in healthy donors and patients with atopic dermatitis, and systemic sclerosis, were calculated by a Mann-Whitney U test. The diagnostic accuracy was evaluated by the area under the receiver operating characteristics (AUROC) curve between the individual dermatological indications and healthy controls. An AUC=0.85 was considered clinically relevant.

Results: Patients with atopic dermatitis presented higher levels of C6A6, C7M, and PRO-C17 compared to healthy donors (p < 0.001, p< 0.001, and p=0.0005, respectively), where C7M was significantly elevated in patients with systemic sclerosis compared to healthy donors (p=0.0019). Neither C6A6 or PRO-C17 could separate between healthy donors and patients with systemic sclerosis. The diagnostic accuracy of C6A6 for separating patients with atopic dermatitis from healthy controls was AUC=1.00, while the C7M biomarker presented an AUC=0.912, and PRO-C17 presented an AUC=0.842. The C7M presented a diagnostic accuracy of an AUC=0.908 for separating healthy donors and patients with systemic sclerosis.

Conclusion: There was a clear link between collagen genetic components and serological biomarkers in skin diseases. This study highlights the possible use of novel non-invasive biomarkers of collagens to describe the disease in patients with atopic dermatitis. In addition, C7M may be a useful biomarker in systemic sclerosis. These biomarkers reflect the downstream effect of different genetic mutations leading to skin disease and may be useful to determine skin involvement in rheumatic diseases, including systemic sclerosis and psoriatic arthritis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/is-skin-disease-a-local-manifestation-of-systemic-tissue-turnover-serological-collagen-biomarkers-provide-important-information-on-skin-diseases-arising-from-mutations-in-collagen-genes/