Department of Pathology Medical College of Georgia at Augusta University, Augusta, GA.
Lab Med. 2020 Nov 2;51(6):592-600. doi: 10.1093/labmed/lmaa012.
Measurement of monoclonal immunoglobulins is a reliable estimate of the plasma cell tumor mass. About 15% of plasma cell myelomas secrete light chains only. The concentration of serum free light chains is insufficient evidence of the monoclonal light chain burden. A sensitive quantitative estimate of serum free monoclonal light chains could be useful for monitoring patients with light chain myeloma. We describe such an assay that does not require mass-spectrometry equipment or expertise.
Serum specimens from patients with known light chain myelomas and controls were subjected to ultrafiltration through a membrane with pore size of 50 kDa. The filtrate was concentrated and tested by immunofixation electrophoresis. The relative area under the monoclonal peak, compared to that of the total involved light chain composition, was estimated by densitometric scanning of immunofixation gels. The proportion of the area occupied by the monoclonal peak in representative densitometric scans was used to arrive at the total serum concentration of the monoclonal serum free light chains.
Using an ultracentrifugation and concentration process, monoclonal serum free light chains were detectable, along with polyclonal light chains, in all 10 patients with active light chain myelomas. Monoclonal light chains were identified in serum specimens that did not reveal monoclonal light chains by conventional immunofixation electrophoresis. The limit of detection by this method was 1.0 mg/L of monoclonal serum free light chains.
The method described here is simple enough to be implemented in academic medical center clinical laboratories and does not require special reagents, equipment, or expertise. Even though urine examination is the preferred method for the diagnosis of light chain plasma cell myelomas, measurement of the concentration of serum free light chains provides a convenient, albeit inadequate, way to monitor the course of disease. The method described here allows effective electrophoretic differentiation of monoclonal serum free light chain from polyclonal serum free light chains and provides a quantitation of the monoclonal serum free light chains in monitoring light chain monoclonal gammopathies.
单克隆免疫球蛋白的测量是浆细胞瘤质量的可靠估计。大约 15%的浆细胞骨髓瘤仅分泌轻链。血清游离轻链的浓度不足以证明单克隆轻链负担。对血清游离单克隆轻链进行敏感的定量估计可能有助于监测轻链骨髓瘤患者。我们描述了一种不需要质谱仪设备或专业知识的检测方法。
对已知患有轻链骨髓瘤和对照的患者的血清标本进行超滤，膜的孔径为 50 kDa。滤过液浓缩后，通过免疫固定电泳进行检测。通过对免疫固定电泳凝胶的密度扫描，估计单克隆峰相对于总受累轻链组成的相对面积。代表性密度扫描中峰面积的比例用于得出血清中单克隆游离轻链的总浓度。
使用超速离心和浓缩过程，在所有 10 例活动性轻链骨髓瘤患者的血清中，可检测到单克隆游离轻链和多克隆轻链。在常规免疫固定电泳未显示单克隆轻链的血清标本中也发现了单克隆轻链。该方法的检测限为 1.0mg/L 的单克隆游离轻链。
这里描述的方法足够简单，可以在学术医疗中心的临床实验室实施，不需要特殊试剂、设备或专业知识。尽管尿液检查是诊断轻链浆细胞骨髓瘤的首选方法，但游离轻链浓度的测量提供了一种方便但不充分的监测疾病过程的方法。这里描述的方法允许有效地将单克隆游离轻链与多克隆游离轻链进行电泳区分，并提供监测轻链单克隆丙种球蛋白病的单克隆游离轻链的定量。
