Andrade-Campos Marcio, Murillo-Flórez Ilda, García-Sanz Ramón, Giraldo Pilar
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Clin Chem Lab Med. 2017 Aug 28;55(10):1598-1604. doi: 10.1515/cclm-2016-0748.
The management of IgM monoclonal gammopathies undetermined significance (IgM-MGUS) and Waldenstrom's macroglobulinemia (WM) may be challenging. Modern immunoassays that quantify specific monoclonal heavy and light chain immunoglobulins are promising for their use in these applications.
Ninety consecutive patients (39 IgM-MGUS, 32 indolent WM [iWM], and 19 WM) seen between January 2007 and March 2014 were analyzed. Heavy/light chain (HLC) and serum free light chains assays (FLC) were determined at diagnosis to study their utility as biomarkers in IgM monoclonal gammopathies.
The HLC involved to uninvolved IgM ratios (iHLC/uHLC) showed a progressive increase when going from IgM-MGUS, to iWM and to WM (p=0.002). Furthermore, an iHLC/uHLC>62 identified a group of iWM patients with a shorter time-to-progression (TTP) (108 vs. 133 months, p=0.033). Separate analysis of the involved and uninvolved components showed that only the suppression of the uninvolvedimmunoglobulin was predictive of shorter TTP (HR=3.04, p=0.03) suggesting that it could be the majorcontributor to the prognostic value of the Hevylite assay. Additionally, a multivariate analysis showed that immunosuppression (either classical immunoparesis or Hevylite immunosuppression) was an independent prognostic factor (p=0.016) reinforcing its relevance in the disease mechanism. Finally, monoclonal sFLC levels were highest in WM patients, with 83% presenting values>60 mg/L.
The results suggest that the levels of immunosuppression and/or the iHLC/uHLC ratio of IgM immunoglobulins measured by Hevylite are associated with greater disease activity which significantly impacts in the outcome of WM patients and may also help in the differentiation of IgMMGUS from iWM.
意义未明的IgM单克隆丙种球蛋白病（IgM-MGUS）和华氏巨球蛋白血症（WM）的管理可能具有挑战性。定量特定单克隆重链和轻链免疫球蛋白的现代免疫测定法在这些应用中具有广阔前景。
对2007年1月至2014年3月期间连续就诊的90例患者（39例IgM-MGUS、32例惰性WM [iWM]和19例WM）进行分析。在诊断时测定重链/轻链（HLC）和血清游离轻链测定（FLC），以研究它们作为IgM单克隆丙种球蛋白病生物标志物的效用。
从IgM-MGUS到iWM再到WM，HLC与未受累IgM的比率（iHLC/uHLC）呈逐渐增加趋势（p = 0.002）。此外，iHLC/uHLC>62可识别出一组疾病进展时间（TTP）较短的iWM患者（108个月对133个月，p = 0.033）。对受累和未受累成分的单独分析表明，只有未受累免疫球蛋白的抑制可预测较短的TTP（HR = 3.04，p = 0.03），这表明它可能是Hevylite测定法预后价值的主要贡献因素。此外，多变量分析表明免疫抑制（经典免疫球蛋白缺乏或Hevylite免疫抑制）是一个独立的预后因素（p = 0.016），强化了其在疾病机制中的相关性。最后，单克隆sFLC水平在WM患者中最高，83%的患者值>60 mg/L。
结果表明，通过Hevylite测定的免疫抑制水平和/或IgM免疫球蛋白的iHLC/uHLC比率与更高的疾病活动度相关，这对WM患者的预后有显著影响，也可能有助于区分IgM-MGUS和iWM。
