Background

Posttransplant lymphoproliferative disorder (PTLD) is a severe complication of solid organ transplantation (SOT). However, there is no consensus on PTLD screening methods. Gammopathies (GP), which occur in 10–25% of SOT recipients, have been linked to subsequent development of PTLD. Therefore, GP detection methods, such as serum protein electrophoresis (SPE), serum protein immunofixation (SIFE), urine protein immunofixation (UIFE) and the quantitative measurement of serum free light chains (SFLC) are candidate methods for PTLD screening.

Objective

We aimed to assess the frequency of PTLD and GP, association of GP with subsequent PTLD, allograft loss or death and the diagnostic performance of SPE/SIFE in PTLD screening. The main objective was to explore, whether GP detection methods can be used to enhance the efficiency of PTLD screening and to formulate a concise algorithm for posttransplantation (post-Tx) follow-up.

Methods

We performed a cohort study on 1677 SOT recipients with SPE/SIFE data who underwent kidney, liver, heart, pancreas, Langerhans islets or multiple organ transplantation at the Institute of Clinical and Experimental Medicine between 1966 and 2015. The median (IQR) of follow-up time was 8.0 (4.0–12.0) years.

Results

The frequencies of PTLD and GP in SOT recipients were 2.8% and 6.4%, respectively. The frequencies of transient GP, GP of undetermined significance and malignant GP were 33%, 63% and 4% respectively. The median time between SOT and GP detection was 2.0 (interquartile range 1.0–7.0) years. GP was associated with a significantly higher risk of PTLD, allograft loss and death, with hazard ratios (95% confidence intervals) of a 6.06 (2.51–14.64), 2.61 (1.49–4.6) and 1.99 (1.2–3.3), respectively. Additionally, GP was associated with 2.98-fold increased risk of allograft loss in kidney transplant patients. SPE diagnostic sensitivity and specificity for PTLD were 14.8% and 93.9%, respectively. PTLD was diagnosed more often and earlier if SPE/SIFE was included in the post-Tx follow-up.

Conclusions

GP after SOT is associated with a high risk of PTLD, allograft loss and poor survival. The combination of SPE, SIFE, SFLC and UIFE is optimal for GP detection. These methods aid in identifying patients who are at risk for PTLD or allograft damage and should be included in regular post-Tx follow-up.

中文翻译：

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1677个实体器官移植受者的免疫球蛋白异常。对移植后随访的影响。

背景

移植后淋巴细胞增生性疾病（PTLD）是实体器官移植（SOT）的严重并发症。但是，关于PTLD筛查方法尚无共识。发生在10％至25％的SOT接受者中的伽玛病（GP）与PTLD的后续发展有关。因此，GP检测方法，如血清蛋白电泳（SPE），血清蛋白免疫固定（SIFE），尿蛋白免疫固定（UIFE）和血清游离轻链的定量测量（SFLC）是PTLD筛选的候选方法。

目的

我们旨在评估PTLD和GP的频率，GP与随后的PTLD的关联，同种异体移植物的丢失或死亡以及SPE / SIFE在PTLD筛查中的诊断性能。主要目的是探讨是否可以使用GP检测方法来提高PTLD筛查的效率，并为移植后（Tx）随访制定简洁的算法。

方法

我们对1966年至2015年之间在临床和实验医学研究所接受SPE / SIFE数据，接受肾脏，肝脏，心脏，胰腺，朗格汉斯胰岛或多器官移植的1677名SOT接受者进行了一项队列研究。启动时间为8.0（4.0-12.0）年。

结果

SOT接受者的PTLD和GP频率分别为2.8％和6.4％。瞬时GP，未定意义GP和恶性GP的频率分别为33％，63％和4％。SOT和GP检测之间的中位时间为2.0年（四分位间距1.0-7.0）年。GP与PTLD，同种异体移植物丢失和死亡的风险显着增加有关，危险比（95％置信区间）分别为6.06（2.51–14.64），2.61（1.49–4.6）和1.99（1.2–3.3）。此外，肾移植患者中GP与同种异体移植丢失风险增加2.98倍相关。SPE对PTLD的诊断敏感性和特异性分别为14.8％和93.9％。如果在Tx之后的随访中包括SPE / SIFE，则PTLD的诊断频率更高，而且诊断更早。

结论

SOT后的GP与PTLD的高风险，同种异体移植物丢失和不良的存活率相关。SPE，SIFE，SFLC和UIFE的组合是GP检测的最佳选择。这些方法有助于识别有PTLD或同种异体移植风险的患者，应纳入常规的Tx术后随访中。