Increased Mac-2 binding protein glycan isomer in patients at risk for late nonrelapse mortality after HSCT
Increased Mac-2 binding protein glycan isomer in patients at risk for late nonrelapse mortality after HSCT
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DOI：
10.1182/bloodadvances.2019000629
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发表时间：
2019-11-12
期刊：
影响因子：
7.5
通讯作者：
Kanda, Yoshinobu
中科院分区：
文献类型：
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作者：
Akahoshi, Yu;Nakasone, Hideki;Kanda, Yoshinobu
巨噬细胞在慢性移植物抗宿主病（cGVHD）的发病机制中发挥着至关重要的作用。我们假设半乳糖凝集素-3、Mac-2 结合蛋白 (M2BP) 或紫藤凝集素 (WFA)(+) -M2BP（称为 M2BP 聚糖异构体 (M2BPGi)）可能有助于巨噬细胞活化，并且纤维化可能与造血干细胞移植 (HSCT) 受者的 cGVHD 和非复发死亡率 (NRM) 相关。首次接受同种异体 HSCT 并存活超过 180 天且无复发的患者被纳入其中。使用发现队列 (n = 55) 和验证队列 1 (n = 55) 评估 3 种 NRM 标志物的预测潜力。当我们在发现队列中使用由受试者操作特征曲线分析确定的阈值时，在发现队列中（5 年时为 15.0% vs 0.0%，P = .001）和验证队列 1 中（5 年时为 34.0% vs 8.4%，P = .014），只有 +180 天的 M2BPGi 与较高的 NRM 显着相关。这一结果在验证队列 2 (n - 50) 中得到了证实。在健康个体或接受自体 HSCT 的患者中，M2BPGi 并未增加。在整个队列中（N = 110），M2BPGi 与肝脏 cGVHD 显着相关，但与其他器官受累无关。在多变量分析中，M2BPGi 是 NRM 的独立危险因素。在尸检病例的免疫荧光染色中，仅在患有cGVHD的肝切片中发现WFA(+)-M2BP阳性巨噬细胞。总之，M2BPGi 可能是 HSCT 后晚期 NRM 的有希望的预测因子，并且与肝脏受累相关。
Macrophages play a crucial role in the pathogenesis of chronic graft-versus-host disease (cGVHD). We hypothesized that galectin-3, Mac-2 binding protein (M2BP), or Wisteria floribunda agglutinin (WFA)(+) -M2BP, called M2BP glycan isomer (M2BPGi), might contribute to macrophage activation, and fibrosis would be associated with cGVHD and nonrelapse mortality (NRM) in hematopoietic stem cell transplant (HSCT) recipients. Patients who underwent their first allogeneic HSCT and survived for >180 days without relapse were included. The predictive potential of the 3 markers for NRM was assessed using the discovery cohort (n = 55) and validation cohort 1 (n = 55). When we used the threshold determined by a receiver operating characteristics curve analysis in the discovery cohort, only M2BPGi at day +180 was significantly associated with a higher NRM in the discovery cohort (15.0% vs 0.0% at 5 years, P = .001) and in validation cohort 1 (34.0% vs 8.4% at 5 years, P = .014). This result was confirmed in validation cohort 2 (n - 50). M2BPGi was not increased in healthy individuals or in patients who received autologous HSCT. In the entire cohort (N = 110), M2BPGi was significantly related to liver cGVHD but not to other organ involvement. In multivariate analyses, M2BPGi was an independent risk factor for NRM. In immunofluorescence staining of autopsy cases, WFA(+)-M2BP-positive macrophages were found only in the liver sections with cGVHD. In conclusion, M2BPGi could be a promising predictor of late NRM after HSCT and was associated with liver involvement.