开发一种甲状旁腺素相关蛋白化学发光免疫分析方法，以评估恶性肿瘤所致体液性高钙血症。

Development of a PTHrP chemiluminescent immunoassay to assess humoral hypercalcemia of malignancy.

机构信息

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States.

出版信息

Clin Biochem. 2022 Jul-Aug;105-106:75-80. doi: 10.1016/j.clinbiochem.2022.04.005. Epub 2022 Apr 14.

DOI:10.1016/j.clinbiochem.2022.04.005

PMID:35429486

Abstract

BACKGROUND

Parathyroid hormone related peptide (PTHrP) measurements are helpful in the evaluation and management of individuals suspected of humoral hypercalcemia of malignancy (HHM).

AIM

To develop a chemiluminescent assay for PTHrP quantitation, establish reference intervals, and evaluate its clinical performance.

METHOD

PTHrP 1-86 was measured using a polyclonal rabbit antibody (capture) and an acridinium ester labeled goat polyclonal antibody for chemiluminescent detection.

RESULTS

Assay imprecision was < 9% (intra-assay) and < 15% (inter-assay). The analytical measuring range was 0.16-50.5 pmol/L. No significant cross-reactivity was observed for PTH (1-84), PTHrP (107-139), and PTHrP (1-36); whereas PTHrP (38-94) showed 8.3% cross-reactivity. Comparison with the pre-existing Mayo assay showed a positive bias: new assay = 2.24 (pre-existing assay)-0.30 and r = 0.96. The reference interval was ≤ 0.7 pmol/L, however, a cut-off of ≤ 4.2 pmol/L yielded increased specificity (98%). Comparison of patients with HHM versus those without HHM resulted in an area under the ROC curve of 0.99. A significant inverse relationship between eGFR and PTHrP was observed (r = 0.738). PTHrP concentrations in patients with Chronic Kidney Disease (CKD) were ≤ 4.2 pmol/L.

CONCLUSION

This assay is specific for PTHrP 1-86. A clinical decision limit of 4.2 pmol/L was sensitive and specific for patients with HHM.

摘要

背景

甲状旁腺激素相关肽（PTHrP）的测量有助于评估和管理疑似恶性肿瘤体液性高钙血症（HHM）的个体。

目的

开发一种用于 PTHrP 定量的化学发光测定法，建立参考区间，并评估其临床性能。

方法

使用多克隆兔抗体（捕获）和吖啶酯标记的山羊多克隆抗体进行 PTHrP 1-86 的化学发光检测。

结果

测定的不精密度<9%（批内）和<15%（批间）。分析测量范围为 0.16-50.5 pmol/L。PTH（1-84）、PTHrP（107-139）和 PTHrP（1-36）无明显交叉反应；而 PTHrP（38-94）表现出 8.3%的交叉反应性。与现有的 Mayo 测定法比较显示出正偏倚：新测定法=2.24（现有的测定法）-0.30，r=0.96。参考区间为≤0.7 pmol/L，但截值为≤4.2 pmol/L 可提高特异性（98%）。将 HHM 患者与无 HHM 患者进行比较，ROC 曲线下面积为 0.99。观察到 eGFR 与 PTHrP 呈显著负相关（r=0.738）。慢性肾脏病（CKD）患者的 PTHrP 浓度≤4.2 pmol/L。