Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
Clin Chem Lab Med. 2023 Jul 24;61(12):2195-2204. doi: 10.1515/cclm-2023-0562. Print 2023 Nov 27.
Heterozygous mutations in the granulin () gene may result in haploinsufficiency of progranulin (PGRN), which might lead to frontotemporal dementia (FTD). In this study, we aimed to perform analytical and clinical validation of a commercial progranulin kit for clinical use.
Analytical validation parameters including assay precision, selectivity, measurement range, dilution linearity, interferences and sample stability were tested according to previously described procedures. For clinical validation, PGRN levels were measured in plasma from 32 cognitively healthy individuals, 52 confirmed mutation carriers, 25 mutation carriers and 216 patients with different neurodegenerative diseases of which 70 were confirmed as non-mutation carriers.
Among the analytical validation parameters, assay precision and repeatability were very stable (coefficients of variation <7 %). Spike recovery was 96 %, the measurement range was 6.25-400 μg/L and dilution linearity ranged from 1:50-1:200. Hemolysis did not interfere with progranulin levels, and these were resistant to freeze/thaw cycles and storage at different temperatures. For the clinical validation, the assay was capable of distinguishing mutation carriers from controls and non- mutation carriers with very good sensitivity and specificity at a cut-off of 57 μg/L (97 %, 100 %, respectively).
In this study, we demonstrate robust analytical and diagnostic performance of this commercial progranulin kit for implementation in clinical laboratory practice. This easy-to-use test allows identification of potential mutation carriers, which may guide further evaluation of the patient. This assay might also be used to evaluate the effect of novel PGRN-targeting drugs and therapies.
颗粒蛋白前体（PGRN）基因的杂合突变可能导致 PGRN 部分功能缺失，从而引发额颞叶痴呆（FTD）。本研究旨在对一种用于临床的商业化 PGRN 试剂盒进行分析和临床验证。
根据先前的描述程序，对分析验证参数，包括精密度、选择性、测量范围、稀释线性、干扰和样品稳定性进行测试。在临床验证中，测量了 32 名认知正常个体、52 名确诊 突变携带者、25 名 突变携带者和 216 名患有不同神经退行性疾病患者的血浆 PGRN 水平，其中 70 名被确认为非突变携带者。
在分析验证参数中，精密度和重复性非常稳定（变异系数<7%）。回收率为 96%，测量范围为 6.25-400μg/L，稀释线性范围为 1:50-1:200。溶血不影响 PGRN 水平，且这些水平对冻融循环和不同温度下的储存具有抵抗力。在临床验证中，该检测在 57μg/L 的截断值下能够很好地区分 突变携带者与对照者和非 突变携带者，具有很好的敏感性和特异性（分别为 97%，100%）。
在这项研究中，我们证明了这种商业化 PGRN 试剂盒具有可靠的分析和诊断性能，可用于临床实验室实践。这种易于使用的检测方法可以识别潜在的 突变携带者，这可能有助于进一步评估患者。该检测方法还可用于评估新型 PGRN 靶向药物和治疗方法的效果。
