多发性骨髓瘤患者血清游离轻链检测及其临床意义

Assessment of serum free light chain of patients with multiple myeloma and clinical significance thereof

目的确定中国人血清游离轻链(sFLC)的正常值,评价 sFLC 在多发性骨髓瘤(MM)患者的诊断、疗效判断中的临床意义。方法自动免疫比浊法检测63例健康人 sFLC 水平,确定其正常参考区间。采用同样方法检测72例 MM 患者不同疾病阶段的 sFLC 水平,通过与传统的 M 蛋白检测方法的比较来评价 sFLC 的临床意义。结果 (1)健康人 sFLC-κ、sFLC-λ的95%参考区间分别为(9～29)mg/L、(15～34)mg/L,sFLC-κ/λ比值的中位值为0.59,100%参考区间为0.27～2.49。(2)初治 MM 患者中,κ增高的 MM(κ-MM)患者的 sFLC-κ、sFLC-λ的95%参考区间分别为(53～14 100)mg/L、(0～97)mg/L,sFLC-κ/λ比值中位值为10.27;λ增高的MM(λ-MM)患者的sFLC-κ、sFLC-λ95%参考区间分别为(9～117)mg/L、(205～6875)mg/L,sFLCκ/λ比值中位值是0.005。MM患者 sFLC-κ、sFLC-λ的95%参考区间与健康人间无交叉重叠。96.4%(26/27)初治 MM 患者的sFLCκ/λ比值异常。(3)健康人 sFLC-κ、sFLC-λ均与年龄呈正相关(P 值分别为0.031、0.01),而sFLCκ/λ比值与年龄无相关性(P=0.861)。初治 MM 患者年龄与 sFLC-κ、sFLC-λ浓度及 sFLCκ/λ比值间均无相关性(P 分别为0.287、0.408、0.471)。(4)对于初治患者,检测κ克隆时比浊法与免疫固定法的敏感性和特异性分别是100% vs 73.7%和100% vs 44.4%;检测λ克隆时比浊法与 IFE 法的敏感性和特异性分别是100% vs 68.8%和100% vs 58.3%。对于治疗后达完全缓解的 MM 患者比浊法仍可以检测到单克隆 M 蛋白的存在。结论首次获得了一个中国人 sFLC-κ、sFLC-λ及 sFLCκ/λ的正常参考区间。自动免疫比浊法检测 sFLC 可以提高 MM 患者的初诊时的阳性率和疗效判断准确率。

Objective To determine the normal range, reference intervals and diagnostic ranges of serum free light chains （sFLC） and to evaluate the clinical significance of serum sFLC in diagnosis of multiple myeloma （MM）. Methods Peripheral blood samples were collected from 63 healthy persons and 72 MM patients, including 35 cases of κ-MM and 37 cases of λ-MM. Immuno-turbidimetry and immunofixation electrophoresis （IFE） were used to detect the serum sFLC and monoclonal element of FLC. The specificity and sensitivity of sFLC were evaluated by comparing the results with those obtained by IFE. Results （ 1 ） The 95% reference interval for sFLC of the healthy persons was （9 - 29） mg/L, and that for sFLC-λ was （ 15 -34） mg/L. The diagnostic interval for sFLCκ/λ of the healthy persons was 0. 59 ,and the 100% reference interval was 0. 27 -2.49. （2）The 95% reference intervals for sFLC-κ and sFLC-λ of the κ-MM patients were （53 - 14 100） mg/L and （0 -97） mg/L respectively, and those of the λ-MM patients were（9 - 117） mg/L and （205 - 6875 ） mg/L respectively. The interval for sFLCκ/λ of the κ-MM and λ- MM patients were 10.27 and 0.005 respectively. （3） In the healthy persons sFLC-κ and sFLC-λ levels were positively correlated with age（ P = 0. 031 and P = 0. 01 ）, however, such correlation did not exist in the MM patients. No correlation between sFLCκ/λ and age was found in both the healthy persons and MM patients （both P 〉 0.05）. （4） Detection and quantification of monoclonal FLC by nephelometry were more sensitive than IFE in serum samples from the patients with MM. Conclusion The reference interval and diagnostic range of sFLC in Chinese have been obtained. Quantification of sFLC proves useful in the diagnosis and monitoring of patients with MM.