严重的同型匹配免疫抑制（IMI）作为意义未明的单克隆球蛋白血症（MGUS）患者病情进展的潜在危险因素。

Severe Isotype-Matched Immunosuppression (IMI) as a Potential Risk Factor for Progression of MGUS Patients.

作者信息

Jiménez Juana J, Pais Tiago M, Barbosa Nuno, Campos Maria Luisa, Díaz Maria Antonia Peñalver, de Larramendi Carmen H

机构信息

Department of Clinical Chemistry, University Hospital Severo Ochoa, Madrid, Spain.

Scientific Department, The Binding Site Iberia, Barcelona, Spain.

出版信息

J Appl Lab Med. 2018 Mar 1;2(5):700-710. doi: 10.1373/jalm.2017.024307.

DOI:10.1373/jalm.2017.024307

PMID:33636869

Abstract

BACKGROUND

Monoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma in virtually every case. However, only a small percentage will progress and at very different rates. In addition, recent data have suggested that MGUS is associated with other comorbidities including infections, suggesting impaired immune function in some MGUS patients. Therefore, we aimed at assessing the value of isotype-matched immunosuppression (IMI; e.g., suppression of an IgAκ in an IgAλ patient), a type of immunosuppression more specific than classical immunoparesis (IP; e.g., IgG and/or IgM suppression in an IgA patient), as a prognostic marker for MGUS progression.

METHODS

The Hevylite assay was used to assess IMI and immunoglobulin ratios in 307 serum samples from a cohort of 248 MGUS patients. Follow-up clinical records were available for 154 individuals.

RESULTS

A greater incidence of IMI (51%) over classical IP (37%) was observed, although both show a progressive increase with higher risk groups. Survival analysis of 154 patients showed that severe IMI (>50% suppression) differentiates 2 groups with significantly different time to progression (P = 0.024) while severe IP does not (P = 0.48). Also, a combination of severe IMI and involved monoclonal immunoglobulin >1.5g/dL by Hevylite (both variables found to be independent prognostic markers in multivariate analysis) identified a group of patients with a median time to progression 6-fold shorter than the remaining group (P < 0.0001).

CONCLUSIONS

These findings indicate a possible role for IMI in the malignant transformation of MGUS patients and a potential utility as a new risk factor.

摘要

背景

意义未明的单克隆丙种球蛋白病（MGUS）几乎在每一例多发性骨髓瘤之前出现。然而，只有一小部分会进展，且进展速度差异很大。此外，最近的数据表明，MGUS与包括感染在内的其他合并症有关，提示部分MGUS患者存在免疫功能受损。因此，我们旨在评估同型匹配免疫抑制（IMI；例如，在IgAλ患者中抑制IgAκ）作为MGUS进展的预后标志物的价值，IMI是一种比经典免疫球蛋白减少（IP；例如，在IgA患者中抑制IgG和/或IgM）更具特异性的免疫抑制类型。

方法

使用Hevylite检测法评估来自248例MGUS患者队列的307份血清样本中的IMI和免疫球蛋白比率。154名个体有随访临床记录。

结果

观察到IMI（51%）的发生率高于经典IP（37%），尽管两者在风险较高的组中均呈逐渐增加。对154例患者的生存分析表明，严重IMI（抑制>50%）可区分出两组进展时间差异显著的患者（P = 0.024），而严重IP则不能（P = 0.48）。此外，严重IMI与Hevylite检测法显示的受累单克隆免疫球蛋白>1.5g/dL相结合（在多变量分析中发现这两个变量均为独立的预后标志物），确定了一组患者，其进展的中位时间比其余组短6倍（P < 0.0001）。