Roblin Elen, Clark Kristina E N, Beesley Claire, Ong Voon H, Denton Christopher P
Department of Rheumatology, Royal Free Hospital, London, UK.
Centre for Rheumatology, University College London, London, UK.
Rheumatol Adv Pract. 2024 Mar 9;8(2):rkae039. doi: 10.1093/rap/rkae039. eCollection 2024.
Using an integrated multi-omic analysis, we previously derived a candidate marker that estimates the modified Rodnan Skin Score (mRSS) and thus the severity of skin involvement in SSc. In the present study we explore technical and biological validation of this composite marker in a well-characterized cohort of SSc patients.
Cartilage oligomeric matrix protein (COMP), collagen type IV (COL4A1), tenascin-C (TNC) and spondin-1 (SPON1) were examined in serum samples from two independent cohorts of patients with dcSSc. The BIOlogical Phenotyping of diffuse SYstemic sclerosis cohort had previously been used to derive the composite marker and Molecular Determinants to Improve Scleroderma (SSc) treatment (MODERNISE) was a novel validation cohort. Multiple regression analysis derived a formula to predict the mRSS based on serum ELISA protein concentration.
The serum concentration of two of the proteins-COMP and TNC-positively correlated with the mRSS, particularly in early dcSSc patients. Interpretable data could not be obtained for SPON1 due to technical limitations of the ELISA. COL4A1 showed a correlation with disease duration but not overall mRSS. Patients receiving MMF showed lower serum concentrations of COMP, COL4A1 and TNC and a lower composite biomarker score not established on treatment. A revised ELISA-based three-protein composite formula was derived for future validation studies.
Although more validation is required, our findings represent a further step towards a composite serum protein assay to assess skin severity in SSc. Future work will establish its utility as a predictive or prognostic biomarker.
我们之前通过综合多组学分析得出了一个候选标志物，该标志物可用于估算改良罗德南皮肤评分（mRSS），进而评估系统性硬化症（SSc）皮肤受累的严重程度。在本研究中，我们在一组特征明确的SSc患者队列中探索了该复合标志物的技术和生物学验证情况。
在两个独立的弥漫性皮肤型SSc（dcSSc）患者队列的血清样本中检测了软骨寡聚基质蛋白（COMP）、IV型胶原（COL4A1）、腱生蛋白-C（TNC）和脊髓灰质炎病毒受体1（SPON1）。弥漫性系统性硬化症队列的生物学表型分析先前已用于推导复合标志物，而改善硬皮病治疗的分子决定因素（MODERNISE）是一个新的验证队列。多元回归分析得出了一个基于血清ELISA蛋白浓度预测mRSS的公式。
两种蛋白质——COMP和TNC的血清浓度与mRSS呈正相关，尤其是在早期dcSSc患者中。由于ELISA的技术限制，无法获得关于SPON1的可解释数据。COL4A1与疾病持续时间相关，但与总体mRSS无关。接受霉酚酸酯（MMF）治疗的患者COMP、COL4A1和TNC的血清浓度较低，且治疗时未建立较低的复合生物标志物评分。推导了一个基于ELISA的修订三蛋白复合公式用于未来的验证研究。
尽管还需要更多验证，但我们的研究结果朝着评估SSc皮肤严重程度的复合血清蛋白检测迈出了进一步的步伐。未来的工作将确定其作为预测或预后生物标志物的效用。
