与健康对照相比,JDM患者PBMC和肌肉中的OtoferlinmRNA表达增加。本研究旨在评估Otoferlin在JDM疾病病理生理学中的作用及其与未经治疗的JDM儿童疾病活动的关系。共有26例未经治疗的JDM(88.5%为女性,92.3%白色,非西班牙裔)和15名健康对照纳入本研究。在治疗前和治疗后几个月通过qRT-PCR测定OtoferlinmRNA表达。对各种细胞表面标记和细胞质耳铁蛋白进行了详细的流式细胞术,以鉴定表达耳铁蛋白的细胞。此外,在6例未经治疗的JDM患者和3例健康对照者中,原位评估了肌耳铁蛋白的表达.与对照组相比,JDM儿童的otoferlin表达显着增加(中位数67.5vs.2.1;p=0.001)。otoferlinmRNA表达与以下疾病活动标记之间存在正相关:疾病活动评分(DAS)-总计(rs=0.62,p<0.001);儿童肌炎评估量表(CMAS)(rs=-0.61,p=0.002);新蝶呤(rs=0.57,p=0.004)和vonWillebrand因子抗原(vWF:Ag)(rs=0.60,p=大多数耳铁蛋白阳性细胞是未转换的B细胞(63-99.4%),其中65-75%表达浆细胞标志物(CD19+,IgM+,CD38hi,CD24-)。这项初步研究的结果表明,otoferlin的表达与肌肉无力有关,使其成为疾病活动的可能生物标志物。此外,B细胞和成浆细胞是表达耳铁蛋白的原代细胞。
Otoferlin mRNA expression is increased in JDM patients\' PBMCs and muscle compared to healthy controls. This
study aims to evaluate the role of
otoferlin in JDM disease pathophysiology and its association with disease activity in untreated children with JDM. A total of 26 untreated JDM (88.5% female, 92.3% white, non-Hispanic) and 15 healthy controls were included in this
study. Otoferlin mRNA expression was determined by qRT-PCR before and a few months after therapy. Detailed flow cytometry of various cell surface markers and cytoplasmic otoferlin was performed to identify cells expressing
otoferlin. In addition, muscle otoferlin expression was evaluated in situ in six untreated JDM patients and three healthy controls. There was a significant increase in otoferlin expression in JDM children compared to controls (Median 67.5 vs. 2.1; p = 0.001). There was a positive correlation between mRNA otoferlin expression and the following disease activity markers: disease activity scores (DAS)-total (rs = 0.62, p < 0.001); childhood myositis assessment scale (CMAS) (rs = -0.61, p = 0.002); neopterin (rs = 0.57, p = 0.004) and von Willebrand factor antigen (vWF: Ag) (rs = 0.60, p = 0.004). Most of the otoferlin-positive cells were unswitched B cells (63-99.4%), with 65-75% of them expressing plasmablast markers (CD19+, IgM+, CD38hi, CD24-). The findings of this pilot
study suggest that
otoferlin expression is associated with muscle weakness, making it a possible biomarker of disease activity. Additionally, B cells and plasmablasts were the primary cells expressing
otoferlin.