Tawalbeh Shefa M, Marin Wilfredo, Morgan Gabrielle A, Dang Utkarsh J, Hathout Yetrib, Pachman Lauren M
Biomedical Engineering Department, State University of New York at Binghamton, Binghamton, New York USA.
School of Pharmacy and Pharmaceutical Sciences, State University of New York at Binghamton, Binghamton, Johnson City, New York USA.
BMC Rheumatol. 2020 Oct 1;4:52. doi: 10.1186/s41927-020-00150-7. eCollection 2020.
Blood accessible biomarkers to assess disease activity and their response to therapies in Juvenile Dermatomyositis (JDM) are urgently needed. This pilot study aims to identify serum protein biomarkers associated with clinical disease activity in untreated JDM and their response to medical therapy.
SomaScan® technology screened JDM patients for 1305 proteins at three points: 1) before start of treatment, 2) while on therapy, and 3) after treatment tapering when patients were clinically inactive. To define disease associated biomarkers, SomaScan® data from untreated JDM patients ( = 8) were compared to SomaScan® data from an independent age-matched healthy control group ( = 12). Longitudinal analysis defined treatment responsive proteins at three time points: untreated (7 samples), treated (7 samples), and clinically inactive (6 samples). To confirm the SomaScan® data, a subset of nine candidate proteins ( tested by ELISA after adding 2 JDM (one untreated, one clinically inactive) serum samples to the same group of JDM girls (8 untreated, 7 treated; 7 clinically inactive) as well as with 17 age, gender, matched healthy controls.
Comparison of untreated JDM versus healthy controls identified 202 elevated and 49 decreased serum proteins in JDM patients with an adjusted -value < 0.001. Only 82 out of 251 identified biomarker candidates responded to treatment while 12 out of these 82 proteins returned to their original untreated disease levels upon therapy tapering. The ELISA testing of the untreated samples for nine candidate proteins confirmed previously known biomarkers (CXCL10 or IP-10, CXCL11 or I-TAC and MCP-1) and identified novel biomarkers including IL-22, Angiopoetin-2, and IL-17B in a cross-sectional analysis comparing 8 untreated JDM and 17 age/gender matched controls. The subsequent longitudinal data by ELISA were not concordant for some biomarkers (IL-22 and IL-17B), but the other biomarkers either normalized or rebounded concordantly.
Blood accessible protein biomarkers reflecting JDM pathophysiology were identified; some of them rebounded after therapy was tapered. Further studies bridging these biomarkers to specific clinical features of JDM are required to confirm the clinical utility of these serum protein biomarkers.
迫切需要可通过血液检测的生物标志物来评估青少年皮肌炎（JDM）的疾病活动度及其对治疗的反应。这项初步研究旨在确定与未经治疗的JDM临床疾病活动度及其对药物治疗反应相关的血清蛋白生物标志物。
SomaScan®技术在三个时间点对JDM患者的1305种蛋白质进行筛查：1）治疗开始前；2）治疗期间；3）治疗逐渐减量且患者临床症状缓解时。为了确定与疾病相关的生物标志物，将未经治疗的JDM患者（n = 8）的SomaScan®数据与独立的年龄匹配健康对照组（n = 12）的SomaScan®数据进行比较。纵向分析确定了三个时间点的治疗反应性蛋白质：未经治疗（7个样本）、治疗中（7个样本）和临床缓解期（6个样本）。为了验证SomaScan®数据，在同一组JDM女孩（8例未经治疗、7例治疗中、7例临床缓解）以及17例年龄、性别匹配的健康对照中，加入2例JDM血清样本（1例未经治疗、1例临床缓解）后，对9种候选蛋白质进行ELISA检测。
未经治疗的JDM患者与健康对照的比较发现，JDM患者中有202种血清蛋白升高，49种血清蛋白降低，校正P值<0.001。在251种已鉴定的生物标志物候选物中，只有82种对治疗有反应，其中12种蛋白质在治疗逐渐减量后恢复到未经治疗时的疾病水平。在比较8例未经治疗的JDM和17例年龄/性别匹配对照的横断面分析中，对9种候选蛋白质的未经治疗样本进行ELISA检测，证实了先前已知的生物标志物（CXCL10或IP-10、CXCL11或I-TAC以及MCP-1），并鉴定出了新的生物标志物，包括IL-22、血管生成素-2和IL-17B。随后通过ELISA获得的纵向数据在某些生物标志物（IL-22和IL-17B）方面不一致，但其他生物标志物要么恢复正常，要么一致反弹。
确定了反映JDM病理生理学的可通过血液检测的蛋白质生物标志物；其中一些在治疗逐渐减量后反弹。需要进一步研究将这些生物标志物与JDM的特定临床特征联系起来，以证实这些血清蛋白生物标志物的临床应用价值。
