Human graft-versus-host disease (GvHD) biology beyond 3 months post-hematopoietic stem cell transplantation (HSCT) is complex. The Applied Biomarker in Late Effects of Childhood Cancer (ABLE/PBMTC1202, NCT02067832) study evaluated the immune profiles in chronic GvHD (cGvHD) and late acute GvHD (L-aGvHD). Peripheral blood immune cell and plasma markers were analyzed at day 100 after HSCT and correlated with GvHD diagnosed according to the NIH cGvHD consensus criteria (NIH-CC). Of 302 children enrolled, 241 were evaluable as a) L-aGvHD, b) cGvHD, c) active L-aGvHD or cGvHD, and d) no cGvHD/L-aGvHD. Significant marker differences, adjusted for major clinical factors, were defined as meeting all 3 criteria: ROC AUC ≥0.60; p-value ≤0.05; and effect ratio ≥1.3 or ≤0.75. Patients with only distinctive features but determined as cGvHD by the adjudication committee (non-NIH-CC) had similar immune profiles to NIH-CC. Both cGvHD and late aGvHD had decreased transitional B cells and increased cytolytic NK cells. cGvHD had additional abnormalities, with increased activated T cells, naïve Th and Tc cells, a loss of CD56bright NKreg cells; and increased ST2 and sCD13. Active L-aGvHD before day 114 had additional abnormalities in naïve Th, naive Treg populations, and cytokines and active cGvHD an increase in PD-1- and decrease in PD1+ memory Treg cells. Unsupervised analysis appeared to show a progression of immune abnormalities from no cGvHD/L-aGvHD to L-aGvHD with the most complex pattern in cGvHD. Comprehensive immune profiling will allow us to better understand how to minimize late aGvHD and cGvHD. Further confirmation in adult and pediatric cohorts are needed.

中文翻译：

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慢性 GvHD 和晚期急性 GvHD 之间的免疫特征差异：ABLE/PBMTC 1202 研究的结果

造血干细胞移植 (HSCT) 后 3 个月后的人类移植物抗宿主病 (GvHD) 生物学是复杂的。儿童癌症晚期影响中的应用生物标志物 (ABLE/PBMTC1202, NCT02067832) 研究评估了慢性 GvHD (cGvHD) 和晚期急性 GvHD (L-aGvHD) 的免疫特征。在 HSCT 后第 100 天分析外周血免疫细胞和血浆标志物，并与根据 NIH cGvHD 共识标准 (NIH-CC) 诊断的 GvHD 相关。在登记的 302 名儿童中，241 名可评估为 a) L-aGvHD、b) cGvHD、c) 活跃的 L-aGvHD 或 cGvHD，以及 d) 无 cGvHD/L-aGvHD。根据主要临床因素调整后的显着标志物差异被定义为满足所有 3 个标准：ROC AUC ≥0.60；p值≤0.05；且效果比≥1.3或≤0.75。仅具有独特特征但被裁决委员会确定为 cGvHD 的患者（非 NIH-CC）具有与 NIH-CC 相似的免疫特征。cGvHD 和晚期 aGvHD 都减少了过渡性 B 细胞和增加了溶细胞性 NK 细胞。cGvHD 有额外的异常，活化的 T 细胞、幼稚 Th 和 Tc 细胞增加，CD56bright NKreg 细胞丢失；并增加 ST2 和 sCD13。第 114 天之前的活性 L-aGvHD 在幼稚 Th、幼稚 Treg 群和细胞因子和活性 cGvHD 中有额外的异常，PD-1- 增加和 PD1+ 记忆 Treg 细胞减少。无监督分析似乎显示免疫异常从无 cGvHD/L-aGvHD 发展到具有 cGvHD 中最复杂模式的 L-aGvHD。全面的免疫分析将使我们能够更好地了解如何最大限度地减少晚期 aGvHD 和 cGvHD。