Renoux Céline, Roland Estelle, Ruet Séverine, Zouaghi Sarah, Michel Marie, Joly Philippe, Feray Cécile, Zhao Fanny, Gavanier Déborah, Gaucherand Pascal, Roumieu Fanny, Cannas Giovanna, Merazga Salima, Connes Philippe, Renom Gilles, Massardier Jérôme, Cheillan David
Laboratoire de Biologie Médicale Multi-Sites (LBMMS), Service de Biochimie et Biologie Moléculaire Grand Est, Hospices Civils de Lyon, 69500 Bron, France.
Centre Régional de Dépistage Néonatal Auvergne Rhône-Alpes (CRDN AuRA), 69003 Lyon, France.
Int J Neonatal Screen. 2024 Nov 26;10(4):77. doi: 10.3390/ijns10040077.
In France, sickle cell disease newborn screening (SCD NBS) has been targeted to at-risk regions since 1984, but generalization to the whole population will be implemented from November 2024. Although tandem mass spectrometry (MS/MS) is already used for the NBS of several inherited metabolic diseases, its application for SCD NBS has not been widely adopted worldwide. The aim of this study was to evaluate a dedicated MS/MS kit (Targeted MS/MS Hemo, ZenTech, LaCAR Company, Liege, Belgium) for SCD NBS and to compare the results obtained with those from an NBS reference center using matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) and cation-exchange high-performance liquid chromatography (CE-HPLC, Variant NBS, Biorad Laboratories, Inc., Hercules, CA, USA) as confirmatory method. The MS/MS Hemo kit was used according to the manufacturer's instructions and performed on a Waters Xevo TQ-D (Waters Corporation, USA). The software provided by the manufacturer was used for the calculation and analysis of peptide signal ratios. Among the 1333 samples, the results of 1324 samples were consistent with the HPLC and/or MALDI-TOF results (1263 FA, 50 FAS, 7 FAC, 1 FAO-Arab, and 3 FS). All the discordant results (one FAS on MS/MS vs. FA in CE-HPLC, one FA on MS/MS vs. FAS in CE-HPLC, seven FS on MS/MS vs. FAS in CE-HPLC) were corrected after modifying the peptide signal ratios thresholds, allowing the MS/MS Hemo kit to achieve near-100% sensitivity and specificity for SCD NBS. In conclusion, the MS/MS Hemo kit appears to be an effective method for SCD NBS, particularly for laboratories already equipped with MS/MS technology. However, these results should be confirmed in a larger cohort including a greater number of positive samples for SCD.
自1984年以来，法国的镰状细胞病新生儿筛查（SCD NBS）一直针对高危地区，但将于2024年11月推广至全体人群。尽管串联质谱（MS/MS）已用于多种遗传性代谢疾病的新生儿筛查，但其在SCD NBS中的应用尚未在全球广泛采用。本研究的目的是评估一款用于SCD NBS的专用MS/MS试剂盒（靶向MS/MS血液检测试剂盒，ZenTech，LaCAR公司，列日，比利时），并将所得结果与使用基质辅助激光解吸/电离飞行时间质谱（MALDI-TOF）和阳离子交换高效液相色谱（CE-HPLC，Variant NBS，伯乐生命医学产品有限公司，美国加利福尼亚州赫拉克勒斯）作为确证方法的新生儿筛查参考中心的结果进行比较。MS/MS血液检测试剂盒按照制造商的说明使用，并在沃特世Xevo TQ-D（美国沃特世公司）上进行检测。制造商提供的软件用于计算和分析肽信号比率。在1333份样本中，1324份样本的结果与HPLC和/或MALDI-TOF结果一致（1263份为FA，50份为FAS，7份为FAC，1份为FAO-阿拉伯型，3份为FS）。所有不一致的结果（1份MS/MS检测为FAS而CE-HPLC检测为FA，1份MS/MS检测为FA而CE-HPLC检测为FAS，7份MS/MS检测为FS而CE-HPLC检测为FAS）在修改肽信号比率阈值后得到纠正，使MS/MS血液检测试剂盒在SCD NBS中实现了接近100%的灵敏度和特异性。总之，MS/MS血液检测试剂盒似乎是一种有效的SCD NBS方法，尤其适用于已配备MS/MS技术的实验室。然而，这些结果应在包括更多SCD阳性样本的更大队列中得到证实。
