Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Cytokine. 2020 Sep;133:155124. doi: 10.1016/j.cyto.2020.155124. Epub 2020 May 13.
Systemic sclerosis or systemic scleroderma (SSc) is an inflammatory autoimmune disease whose pathogenesis remains ambiguous; however, epigenetics, including long noncoding RNAs (lncRNAs) is an emerging paradigm. To date, the expression, role and clinical significance of most lncRNAs in SSc remain unelucidated. Herein, we investigated the plasma expression profiles of lncRNAs; ANCR, TINCR, HOTTIP, and SPRY4-IT1, which were linked to skin biology, in SSc patients and its subtypes, their potential as diagnostic tools and their correlations with autoantibodies and disease manifestations. Sixty-three SSc patients and thirty-five healthy volunteers were recruited. Autoantibody profile (anti-Scl-70, anti-centromere, anti-RNA polymeraseIII, anti-ribonucleoprotein, antinuclear, and anti-phospholipid antibodies) was determined. lncRNAs analysis was conducted using RT-qPCR. Plasma TINCR, HOTTIP, and SPRY4-IT1 upregulation and ANCR downregulation were observed in SSc patients compared with controls. SPRY4-IT1 was superior in SSc diagnosis in ROC analysis and predicted its risk in multivariate logistic analysis. Plasma SPRT4-IT1 was higher in diffuse than limited SSc. SPRY4-IT1 and HOTTIP were positively correlated with modified Rodnan skin score while ANCR showed a negative correlation only in limited SSc. ANCR and TINCR were positively correlated with disease duration and ESR, respectively. ANCR and SPRY4-IT1 were positively correlated with pulmonary hypertension. HOTTIP was positively correlated with antinuclear antibody. SPRY4-IT1 was positively correlated with HOTTIP in the whole group, and with TINCR only in diffuse SSc. We introduce plasma SPRY4-IT1, HOTTIP, ANCR and TINCR as novel candidate biomarkers for SSc, with SPRY4-IT1 could predict SSc diagnosis and discriminate its subtypes. Our findings widen the epigenetic landscape of SSc and provide surrogates for future predictive studies.
系统性硬化症或系统性硬皮病（SSc）是一种炎症性自身免疫性疾病，其发病机制仍不清楚；然而，表观遗传学，包括长非编码 RNA（lncRNA），是一个新兴的范例。迄今为止，大多数 lncRNA 在 SSc 中的表达、作用和临床意义仍不清楚。在此，我们研究了与皮肤生物学相关的 lncRNA 的血浆表达谱，包括 ANCR、TINCR、HOTTIP 和 SPRY4-IT1，在 SSc 患者及其亚型中的表达，它们作为诊断工具的潜力及其与自身抗体和疾病表现的相关性。共招募了 63 名 SSc 患者和 35 名健康志愿者。测定了自身抗体谱（抗 Scl-70、抗着丝点、抗 RNA 聚合酶 III、抗核糖核蛋白、抗核和抗磷脂抗体）。采用 RT-qPCR 进行 lncRNA 分析。与对照组相比，SSc 患者的血浆 TINCR、HOTTIP 和 SPRY4-IT1 上调，ANCR 下调。在 ROC 分析中，SPRY4-IT1 在 SSc 诊断中更具优势，并在多变量逻辑分析中预测其风险。弥漫性 SSc 患者的血浆 SPRT4-IT1 高于局限性 SSc。SPRY4-IT1 和 HOTTIP 与改良 Rodnan 皮肤评分呈正相关，而 ANCR 仅在局限性 SSc 中呈负相关。ANCR 和 TINCR 分别与疾病持续时间和 ESR 呈正相关。ANCR 和 SPRY4-IT1 与肺动脉高压呈正相关。HOTTIP 与抗核抗体呈正相关。SPRY4-IT1 在整个组中与 HOTTIP 呈正相关，仅在弥漫性 SSc 中与 TINCR 呈正相关。我们将血浆 SPRY4-IT1、HOTTIP、ANCR 和 TINCR 引入 SSc 的新型候选生物标志物，其中 SPRY4-IT1 可预测 SSc 的诊断并区分其亚型。我们的发现拓宽了 SSc 的表观遗传学景观，并为未来的预测研究提供了替代物。
