Detection and diagnostic utility of paraproteins in body fluids

研究各种体液中的免疫球蛋白，特别是血清、尿液和脑脊液中的免疫球蛋白，对了解各种疾病的发病机制以及疾病的诊断和监测具有重要意义。蛋白质电泳和免疫固定电泳是鉴定体液中蛋白质异常和检测异常免疫球蛋白（副蛋白）的关键技术。副蛋白是浆细胞克隆或寡克隆增殖的产物，因此可以代表全免疫球蛋白、游离重链和/或游离轻链免疫球蛋白。然而，伪原蛋白的出现阻碍了原蛋白的正确鉴定。假原蛋白是正常存在的蛋白质，在蛋白质电泳模式中模仿单克隆蛋白。在过去的一年里，我们观察到在现有文献中没有描述的尿伪副蛋白的新病例。利用各种分析技术的组合（例如琼脂糖和聚丙烯酰胺凝胶电泳，免疫电泳和质谱），我们现在正在充分鉴定这些假原蛋白。在一项合作研究中，我们研究了蛋白电泳、免疫电泳和免疫固定电泳作为家族性Waldenstrm巨球蛋白血症高危表型的预测因子。蛋白质电泳用于检测、评估和随访单克隆γ病条件，如Waldenstrm巨球蛋白血症。免疫固定电泳是目前最常用的单克隆伽玛病等分型方法，因为它相对于免疫电泳具有更高的灵敏度。利用这些方法，对3个家族的46名成员（29名亲属和17名非血系配偶）的多例Waldenstrm巨球蛋白血症进行了可能的单克隆γ病研究。我们发现，在家族背景下，免疫固定电泳检测到的小单克隆带可能具有生物学意义，既可以作为表型生物标志物，也可以作为瓦尔登斯特罗姆巨球蛋白血症高风险的预测因子。多克隆免疫球蛋白M也可能是Waldenstrm巨球蛋白血症家族遗传易感性的标志。需要更大规模的研究来证实这些观察结果。

Study of immunoglobulins in various body fluids, especially in serum, urine and cerebrospinal fluid is important for understanding the pathomechanism of a variety of diseases and for diagnosing and monitoring diseases. Protein electrophoresis and immunofixation electrophoresis are key techniques to identifiy protein abnormalities and to detect abnormal immunoglobulins (paraproteins) in body fluids. The paraproteins are the products of clonal or oligoclonal proliferation of plasma cells and, as such, may represent full immunoglobulins, free heavy chains, and/or free light chains of immunoglobulins. Correct identification of paraproteins can be hampered, however, by the occurrence of pseudoparaproteins. Pseudoparaproteins are normally occurring proteins that mimic monoclonal-proteins in protein electrophoretic patterns. Over the past year, we have observed new cases of urine pseudoparaproteins that had not been described in the existing literature. Using a combination of various analytical techniques (e.g., electrophoresis in agarose and polyacrylamide gel, immunoelectrophoresis, and mass spectrometry), we are now in the process to fully identify these pseudoparaproteins. In a collaborative study, we investigated protein electrophoresis, immunoelectrophoresis and immunofixation electrophoresis as predictors for high-risk phenotype in familial Waldenstrm macroglobulinemia. Protein electrophoresis is used for the detection, evaluation and follow-up of monoclonal gammopathy conditions such as Waldenstrm macroglobulinemia. Immunofixation electrophoresis is currently the most common method for isotyping of monoclonal gammopathy because of its superior sensitivity relative to immunoelectrophoresis. Using these methods, possible monoclonal gammopathy was studied in 46 members (29 relatives and 17 nonbloodline spouses) from 3 families with multiple cases of Waldenstrm macroglobulinemia. We found that small monoclonal bands detected by immunofixation electrophoresis in a familial context may be biologically meaningful, both as phenotypic biomarkers and, possibly, as predictors of high risk for Waldenstrm macroglobulinemia. Polyclonal immunoglobulin M may also be a marker of genetic susceptibility in Waldenstrm macroglobulinemia families. Larger studies are needed to confirm these observations.