低磷酸血症(HPP)的特征是组织非特异性碱性磷酸酶(TNSALP)活性低。酶替代疗法asfotasealfa已被批准用于儿童期发作形式的HPP。MicroRNAs(miRNAs)已经成为一种新型的疾病生物标志物,在治疗监测中具有潜在的应用。循环miRNA在基线分析,一名49岁的患有儿童期HPP的女性的1、2、4和16个月,慢性肌肉骨骼疼痛,和非创伤性骨折之前的酶替代疗法。使用miRNeasyMiniKit(Qiagen,德国),RealSeq生物科学套件(圣克鲁斯,美国)与miND加标对照试剂盒(TAmiRNA,奥地利)和IlluminaNovaSeq6000SP1流动池(圣地亚哥,美国)。简要疼痛量表严重程度和干扰评分(BPI-S/BPI-I),疲劳严重程度量表(FSS),患者总体改善印象(PGI-I),西安大略省和麦克马斯特大学髋关节残疾和骨关节炎结果评分(WOMAC),纤维肌痛影响问卷(FIQ),6分钟步行测试(6-MWT),椅子上升测试(CRT),在基线和治疗期间的不同时间点进行手握测力(HD).在超过800个筛查中,基于24个HPP患者和24个健康对照之间的表达谱差异选择了84个miRNA。六个miRNA显示出清晰的图形趋势,并上调或下调≥50%的读数/百万(rpm)。其中包括hsa-let-7i-5p(+50%),hsa-miR-1-3p(-66.66%),hsa-miR-1294(+63.63%),hsa-miR-206(-85.57%),hsa-miR-375-3p(-71.43%),hsa-miR-624-5p(+69.44%)。hsa-miR-1-3p和hsa-miR-206被鉴定为肌肉特异性miRNA。hsa-mir-375-3p,负调节成骨作用,被大幅下调。就患者报告的结果而言,BPI-S,BPI-I,FSS,PGI-I,WOMAC,FIQ下降了-58.62%,-68.29%,-33.33%,-75.00%,-63.29%,和-43.02%,分别。6-MWT提高了+33.89%,CRT提高了-44.46%。HD测量的右手/左手的平均握力提高了+12.50%和+23.53%,分别。用asfotasealfa治疗期间的miRNA谱变化,伴随功能测试和生活质量评分的改善。
Hypophosphatasia (HPP) is characterized by low activity of tissue nonspecific alkaline phosphatase (TNSALP). The enzyme replacement therapy asfotase alfa has been approved for childhood-onset forms of HPP. MicroRNAs (miRNAs) have emerged as a novel disease biomarker, with potential application in therapy monitoring. Circulating miRNAs were analyzed at baseline, months 1, 2, 4, and 16 in a 49-yr-old woman with childhood-onset HPP, chronic musculoskeletal pain, and non-traumatic fractures prior to enzyme replacement therapy. Serum RNA was extracted and sequenced using miRNeasy Mini Kit (Qiagen, Germany), RealSeq Biosciences Kit (Santa Cruz, US) together with miND spike-in control kit (TAmiRNA, Austria) and Illumina NovaSeq 6000 SP1 flow cell (San Diego, US). Brief Pain Inventory Severity and Interference scores (BPI-S/BPI-I), fatigue severity scale (FSS), Patient Global Impression of Improvement (PGI-I), Western Ontario and McMaster university hip disability and osteoarthritis outcome score (WOMAC), fibromyalgia impact questionnaire (FIQ), 6-Minute Walking Test (6-MWT), chair-rise-test (CRT), and handgrip dynamometry (HD) were performed at baseline and different timepoints during the therapy. Out of >800 screened, 84 miRNAs were selected based on differences in expression profiles between 24 HPP patients and 24 healthy controls. Six miRNAs showed a clear graphic trend and were up- or downregulated by ≥50% reads per million (rpm). These included hsa-let-7i-5p (+50%), hsa-miR-1-3p (-66.66%), hsa-miR-1294 (+63.63%), hsa-miR-206 (-85.57%), hsa-miR-375-3p (-71.43%), and hsa-miR-624-5p (+69.44%). hsa-miR-1-3p and hsa-miR-206 were identified as muscle-specific miRNAs. hsa-mir-375-3p, which negatively regulates osteogenesis, was significantly downregulated. In terms of patient-reported outcomes, BPI-S, BPI-I, FSS, PGI-I, WOMAC, and FIQ showed a reduction by -58.62%, -68.29%, -33.33%, -75.00%, -63.29%, and -43.02%, respectively. 6-MWT improved by +33.89% and CRT by -44.46%. Mean hand grip strength of the right/left hand measured by HD improved by +12.50% and + 23.53%, respectively. miRNA profile changes during the therapy with asfotase alfa, accompanying improvements in functionality tests and quality of life scores.