Detection and diagnostic utility of paraproteins in body fluids

研究各种体液，特别是血清、尿液和脑脊液中的免疫球蛋白对于了解各种疾病的病理机制以及诊断和监测疾病具有重要意义。蛋白质电泳和免疫固定电泳是鉴定蛋白质异常和检测体液中异常免疫球蛋白（副蛋白）的关键技术。副蛋白是浆细胞的克隆或寡克隆增殖的产物，因此可以代表完整的免疫球蛋白、游离重链和/或免疫球蛋白的游离轻链。然而，假副蛋白的出现会妨碍副蛋白的正确鉴定。假副蛋白是在蛋白质电泳图谱中模拟单克隆蛋白的正常存在的蛋白质。在过去的一年中，我们观察到新的情况下，尿假副蛋白，没有在现有的文献中描述。使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、免疫电泳和质谱法），我们现在正在完全鉴定这些假副蛋白。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瓦尔登斯特伦巨球蛋白血症高危表型的预测因子。蛋白电泳用于单克隆丙种球蛋白病的检测、评估和随访，如瓦尔登斯特伦巨球蛋白血症。免疫固定电泳是目前最常用的单克隆丙种球蛋白病亚型分型方法，因为其相对于免疫电泳具有上级灵敏度。使用这些方法，可能的单克隆丙种球蛋白病进行了研究，在46名成员（29名亲属和17名非血统的配偶），从3个家庭的多例Waldenstrm巨球蛋白血症。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是生物学意义，作为表型生物标志物，并可能作为高风险的Waldenstrm巨球蛋白血症的预测因子。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.