Böer Klas, Deufel Thomas
Institut für Klinische Chemie und Laboratoriumsdiagnostik, Friedrlich-Schiller University Jena, Jena, Germany.
Clin Chem Lab Med. 2009;47(9):1109-15. doi: 10.1515/CCLM.2009.254.
Detection of plasma cell dyscrasias (PCD) requires screening of serum and urine for monoclonal proteins. Several studies have demonstrated increased sensitivity and specificity when measurement of serum free light chain (SFLC) is part of the screening protocol. In addition, omission of immunofixation (IFE) in the standard work-up that includes SFLC assay has been proposed. This study attempts to define the role of the SFLC assay in a screening strategy limited to serum only. It compares outcomes to a serum-only screening strategy that omits serum IFE.
Serum from 691 patients was analysed for the presence of monoclonal protein using standard serum IFE, serum protein electrophoresis (SPE) and measurement of SFLC. Data were analysed retrospectively.
Specificity and sensitivity of abnormal SFLC-ratios for the detection of monoclonal protein using IFE were 96% and 41%, respectively. Eighteen patients with negative monospecific and Bence Jones IFE, but abnormal SFLC-ratios were identified. In most cases, this could be attributed to kidney and inflammatory disease or haematological disorders. In four cases, this resulted in further diagnostic investigation and light chain disease was later detected in two cases. Light chain disease was confirmed in one case but not confirmed in the other patient. In 14 patients, Bence Jones IFE was negative, although the concentrations of SFLC suggested the presence of monoclonal Bence Jones protein at concentrations detectable by IFE. Thus, either the anti-serum failed at detection, there was polymerisation of the free light chains or the SFLC assay overestimated protein concentrations. Simulating a work-up that included IFE only if abnormalities were detected by SPE or the SFLC assay would have resulted in 26% fewer IFEs being performed, but three patients with monoclonal proteins by IFE would have been missed.
Abnormal SFLC concentrations are neither sensitive nor specific for the detection of monoclonal proteins by IFE. Not all PCD are accompanied by excessive production of SFLC, and several other conditions, such as renal disease are associated with increased SFLC concentrations. An abnormal SFLC-ratio is a specific marker for PCD, and occurs primarily in patients with haematological disease. If renal and inflammatory diseases are excluded, this should prompt further diagnostic investigation. Screening of serum without performing an IFE as a standard procedure leads to a reduction of sensitivity when compared to screening of serum that includes IFE.
浆细胞异常增殖性疾病（PCD）的检测需要对血清和尿液进行单克隆蛋白筛查。多项研究表明，当血清游离轻链（SFLC）检测作为筛查方案的一部分时，敏感性和特异性会提高。此外，有人提议在包括SFLC检测的标准检查流程中省略免疫固定电泳（IFE）。本研究旨在确定SFLC检测在仅局限于血清的筛查策略中的作用。并将其结果与省略血清IFE的仅血清筛查策略进行比较。
使用标准血清IFE、血清蛋白电泳（SPE）和SFLC检测分析691例患者血清中是否存在单克隆蛋白。对数据进行回顾性分析。
使用IFE检测单克隆蛋白时，异常SFLC比值的特异性和敏感性分别为96%和41%。确定了18例单特异性和本周氏蛋白IFE阴性但SFLC比值异常的患者。在大多数情况下，这可归因于肾脏疾病、炎症性疾病或血液系统疾病。在4例患者中，这导致了进一步的诊断检查，后来在2例患者中检测到轻链病。1例患者确诊为轻链病，另1例未确诊。在14例患者中，本周氏蛋白IFE阴性，尽管SFLC浓度提示存在IFE可检测浓度的单克隆本周氏蛋白。因此，要么抗血清检测失败，要么游离轻链发生聚合，要么SFLC检测高估了蛋白浓度。模拟仅在SPE或SFLC检测发现异常时才进行IFE的检查流程，IFE检查次数将减少26%，但会漏诊3例IFE检测显示存在单克隆蛋白的患者。
SFLC浓度异常对通过IFE检测单克隆蛋白既不敏感也无特异性。并非所有PCD都伴有SFLC过度产生，其他一些情况，如肾脏疾病也与SFLC浓度升高有关。异常SFLC比值是PCD的特异性标志物，主要发生在血液系统疾病患者中。如果排除肾脏和炎症性疾病，这应促使进一步的诊断检查。与包括IFE的血清筛查相比，不将IFE作为标准程序进行血清筛查会导致敏感性降低。
