Sachchithanantham Sajitha, Berlanga Oscar, Alvi Azra, Mahmood Shameem A, Lachmann Helen J, Gillmore Julian D, Hawkins Philip N, Harding Stephen, Wechalekar Ashutosh D
Centre for Amyloidosis and Acute Phase Proteins, University College London (Royal Free Campus), London, UK.
The Binding Site Group Ltd., Birmingham, UK.
Br J Haematol. 2017 Nov;179(4):575-585. doi: 10.1111/bjh.14908. Epub 2017 Oct 8.
Cardiac involvement and presenting dFLC (difference between involved and uninvolved free light chains) are independent predictors of outcome in systemic AL amyloidosis. These markers have limited prognostic utility in patients surviving the initial months following diagnosis. Here we assessed immunoparesis, as determined by novel heavy+light chain (HLC) immunoassays, as a prognostic marker for survival in AL amyloidosis. HLC measurements identified immunoparesis of at least one immunoglobulin (Ig) isotype in 145 (85%) patients; and severe immunoparesis (≥2 Ig isotypes suppressed by >50% below normal levels) in 29 (17%) patients. Median overall survival (OS) on intention to treat (ITT) analysis was 26·2 months. In the ITT cohort, dFLC >180 mg/l was associated with shorter OS (P = 0·05); whereas HLC immunoparesis was not prognostic. On a landmark analysis of 127 patients alive at 6 months, presenting dFLC was not prognostic for OS (P = 0·33) and severe HLC immunoparesis trended towards poorer survival (20·2 vs. 42·8 months; P = 0·09). In the subset of patients with cardiac involvement, severe HLC immunoparesis conferred very poor outcome (median OS 8·8 vs. 29·9 months, P = 0·007). In conclusion, severe HLC immunoparesis is an independent marker of long-term poor prognosis in AL patients with cardiac involvement. The pathophysiological significance of this observation needs further study.
心脏受累和出现的游离轻链差异（受累与未受累游离轻链之间的差异）是系统性AL淀粉样变性预后的独立预测因素。这些标志物在诊断后最初几个月存活的患者中预后效用有限。在此，我们评估了通过新型重链 + 轻链（HLC）免疫测定确定的免疫球蛋白缺乏，作为AL淀粉样变性生存的预后标志物。HLC测量在145例（85%）患者中识别出至少一种免疫球蛋白（Ig）同种型的免疫球蛋白缺乏；29例（17%）患者存在严重免疫球蛋白缺乏（≥2种Ig同种型被抑制至低于正常水平50%以上）。意向性治疗（ITT）分析的中位总生存期（OS）为26.2个月。在ITT队列中，dFLC>180 mg/l与较短的OS相关（P = 0.05）；而HLC免疫球蛋白缺乏无预后意义。对6个月时存活的127例患者进行的标志性分析显示，出现的dFLC对OS无预后意义（P = 0.33），严重HLC免疫球蛋白缺乏有生存较差的趋势（20.2对42.8个月；P = 0.09）。在有心脏受累的患者亚组中，严重HLC免疫球蛋白缺乏导致预后极差（中位OS 8.8对29.9个月，P = 0.007）。总之，严重HLC免疫球蛋白缺乏是有心脏受累的AL患者长期预后不良的独立标志物。这一观察结果的病理生理意义需要进一步研究。
