冷球蛋白、蛋白电泳和血清免疫球蛋白对干燥综合征患者淋巴瘤发生的预后价值。一项回顾性队列研究。

Prognostic value of cryoglobulins, protein electrophoresis, and serum immunoglobulins for lymphoma development in patients with Sjögren's syndrome. A retrospective cohort study.

作者信息

Kimman Jesse, Bossuyt Xavier, Blockmans Daniel

机构信息

a Department of General Internal Medicine , University Hospitals Leuven, Katholieke Universiteit Leuven , Leuven , Belgium.

b Department of Laboratory Medicine, Immunology , University Hospitals Leuven, Katholieke Universiteit Leuven , Leuven , Belgium.

出版信息

Acta Clin Belg. 2018 Jun;73(3):169-181. doi: 10.1080/17843286.2017.1373966. Epub 2017 Oct 3.

DOI:10.1080/17843286.2017.1373966

PMID:28971741

Abstract

BACKGROUND

Patients with Sjögren's syndrome (SS) have a considerable higher risk of lymphoma development.

OBJECTIVES

To determine the incidence of lymphoma and the value of biomarkers to predict lymphoma development in patients with SS.

METHODS

Clinical files of all patients with a presumed diagnosis of SS between 1991 and 2016 were retrospectively reviewed for the development of lymphoma. Biochemical data were plotted as a function of the relative time before and after the lymphoma diagnosis (for patients who developed lymphoma) or before the last available blood test (for patients who did not develop lymphoma). Correlations between several biochemical parameters and development of lymphoma were analyzed by logistic regression. In order to evaluate the evolution of cryoglobulins, a random effect model with random intercepts was used.

RESULTS

Sixteen patients developed a lymphoma (prevalence 8.9%; median follow-up 6 years). Cryoglobulins were significantly higher in these patients (n = 16), when compared to the rest of patients (n = 164) without lymphoma (121 ± 250 versus 8 ± 24.9 mg/L for IgG; 231 ± 422 versus 13 ± 30 mg/L for IgM; 10 ± 20 versus 1 ± 4 mg/L for IgA in the cryoprecipitate). Cryoglobulin-levels were significantly more increasing (p-values for IgG = 0.0007; for IgM = 0.0123; and for IgA in the cryoprecipitate <0.0001) in the time period before the lymphoma diagnosis (patients with lymphoma) compared to the time period before the last available blood test (patients without lymphoma). Also low (i.e. under the detection limit) C3 (OR 13.9) or C4 (OR 7.1) levels, a progressively decreasing total complement activity (OR 6.6), progressively decreasing gammaglobulins (OR 13.4), a persistent detection of monoclonal bands (OR 14.6) on protein electrophoresis, a persistent low or decreasing serum IgG (OR 18), and decreasing IgM-serum levels (OR 17.7) were significantly associated with lymphoma.

CONCLUSION

Periodically follow-up of laboratory markers, such as cryogloblins, over time proved to be an accurate way to predict lymphoma.

摘要

背景

干燥综合征（SS）患者发生淋巴瘤的风险显著更高。

目的

确定淋巴瘤的发病率以及生物标志物对预测SS患者淋巴瘤发生的价值。

方法

回顾性分析1991年至2016年间所有疑似诊断为SS患者的临床档案，以了解淋巴瘤的发生情况。将生化数据绘制成淋巴瘤诊断前后（针对发生淋巴瘤的患者）或最后一次可用血液检测前（针对未发生淋巴瘤的患者）相对时间的函数。通过逻辑回归分析几个生化参数与淋巴瘤发生之间的相关性。为了评估冷球蛋白的变化情况，使用了具有随机截距的随机效应模型。

结果

16例患者发生了淋巴瘤（患病率8.9%；中位随访6年）。与其余未发生淋巴瘤的患者（n = 164）相比，这些患者（n = 16）的冷球蛋白水平显著更高（冷沉淀物中IgG：121±250对8±24.9mg/L；IgM：231±422对13±30mg/L；IgA：10±20对1±4mg/L）。与最后一次可用血液检测前（未发生淋巴瘤的患者）相比，淋巴瘤诊断前时间段（发生淋巴瘤的患者）内冷球蛋白水平显著升高更多（IgG的p值 = 0.0007；IgM的p值 = 0.0123；冷沉淀物中IgA的p值<0.0001）。此外，低（即低于检测限）C3（比值比13.9）或C4（比值比7.1）水平、总补体活性逐渐降低（比值比6.6）、γ球蛋白逐渐降低（比值比13.4）、蛋白电泳上持续检测到单克隆条带（比值比14.6）、持续低或降低的血清IgG（比值比18）以及降低的IgM血清水平（比值比17.7）与淋巴瘤显著相关。