血清游离轻链检测在原发性系统性淀粉样变性中的临床意义

The clinical significance of serum free light chain in primary systemic amyloidosis

目的 探讨血清游离轻链（sFLC）检测在原发性系统性（AL）淀粉样变性诊断和治疗中的意义.方法 收集我院2005年10月-2010年5月收治的25例AL淀粉样变性患者,男18例,女7例,平均年龄54（47～77）岁.采用免疫比浊法测定sFLC,以sFLC κ/λ比值判断单克隆轻链的类型,并与血清免疫固定电泳（IFE）、免疫组化方法比较敏感性.其中9例进行了治疗,观察治疗前后sFLC变化.结果 25例AL淀粉样变性患者中κ型2例,λ型23例.骨髓平均浆细胞比例3.5%（0～15%）.19例（76%）患者的sFLC数值和κ/λ比值均异常,IFE阳性者为17例（68%）,sFLC敏感性与IFE相当（P=0.727）.21例（84%）患者肾活检和（或）肠黏膜活检病理组织免疫组化检测阳性.sFLC联合IFE阳性率88%,免疫组化联合sFLC或IFE阳性率均为96%.治疗后4例血液学缓解的患者器官功能均改善,5例未获缓解者病情稳定或进展.结论 sFLC测定是一种敏感的M蛋白定性定量方法,初步显示治疗后sFLC明显下降和（或）κ/λ比值恢复正常者,器官功能改善比例高,sFLC是AL淀粉样变性诊断的重要指标,并对疗效判定可能有帮助.

Objective To evaluate the diagnostic and therapeutic significance of serum free light chain （sFLC） in primary systemic（AL） amyloidosis. Methods Twenty-five patients with AL amyloidosis,including 18 men and 7 women with a mean age of 54（47-77） years old, were enrolled from October, 2005to May, 2010. sFLC was measured by immunoturbidimetric assay. The type of monoclonal light chain was judged upon sFLC κ/λ and its sensibility was compared with serum immunofixation and immunohistochemical analysis. Four patients were treated with M （T）D （melphalan/thalidomideand, dexamethasone）, one with VD （velcade and dexamethasone） and four with high-dose melphalan followed by autologous stem cell support. The changes of sFLC were serially determined before and after treatment. Results Among the 25 patients with AL amyloidosis, two were κ light chains of precursor protein and 23 were λ light chains. Mean plasma cell in bone marrow was 3.5% （0-15%）. Nineteen （76%） patients had abnormal elevated sFLC and abnormal κ/λ ratios, and 17（68% ） patients with immunofixation positive. The sFLC test had similar sensitivity as serum immunofixation （P = 0. 727 ）. Twenty-one （84%） patients were shown to have either κor λ immunoreactive amyloid deposits on biopsied tissues. The sFLC test combined with serum immunofixation allowed the M protein to be detected in 22 （88%） patients. The positive rates of immunohistochemical analysis combined with sFLC test and/or serum immunofixation were 96%. Four patients with hematologic response showed obvious improvement in visceral organ involvement, but illness of 5 patients without hematologic response kept stable or progressed. Conclusions sFLC test is a sensitive qualitative and quantitative method to detect M protein. Preliminary data show the patients with obvious sFLC level decrease and/or κ/λ recovery to normal may have a high percentage of improved organs function. sFLC is critical index in diagnosing AL amyloidosis, which might help efficacy assessment.