Gonçalves Matheus Vescovi, Yamamoto Mihoko, Kimura Eliza Yurico Sugano, Colturato Vergílio Antônio Rensi, de Souza Mair Pedro, Mauad Marcos, Ikoma Maura Valerio, Novis Yana, Rocha Vanderson, Ginani Valeria Cortez, Wanderley de Oliveira Felix Olga Margareth, Seber Adriana, Kerbauy Fabio Rodrigues, Hamerschlak Nelson, Orfao Alberto, Rodrigues Celso Arrais
Disciplina de Hematologia e Hemoterapia, Universidade Federal de São Paulo, São Paulo, Brazil.
Disciplina de Hematologia e Hemoterapia, Universidade Federal de São Paulo, São Paulo, Brazil.
Biol Blood Marrow Transplant. 2015 Jul;21(7):1223-9. doi: 10.1016/j.bbmt.2015.03.010. Epub 2015 Mar 17.
Dendritic cells (DCs) are antigen-presenting cells that drive immune responses and tolerance and are divided in different subsets: myeloid DCs (mDCs: lineage-; HLA-DR+, 11c+), plasmacytoid dendritic cells (pDCs: HLA-DR+, CD123+), and monocyte-derived DCs (moDC: lineage-, 11c+, 16+). After hematopoietic stem cell transplantation (HSCT), low DC counts in the recipients' peripheral blood (PB) have been associated with worse outcomes, but the relevance of DC graft content remains unclear, and there are few data in the setting of unrelated donor HSCT. We evaluated the DC graft content and monitored DC recovery in PB from 111 HSCT recipients (median age, 17 years; range 1 to 74), who received bone marrow (46%), umbilical cord blood (32%), or PB (22%) from unrelated (81%) or related donors (19%). In 86 patients with sustained allogeneic recovery, patients with higher counts of all DC subsets (pDC, mDC, and moDC) 3 weeks after engraftment had lower incidence of nonrelapse mortality (NMR) and acute graft-versus-host disease (aGVHD) and better survival. pDC counts were associated with more striking results: patients with higher pDC counts had much lower incidences of NRM (3% versus 47%, P < .0001), lower incidence of aGVHD (24% versus 67%, P < .0001), and better overall survival (92% versus 45%, P < .0001). In contrast, higher pDC counts in the graft was associated with an increased risk of aGVHD (55% versus 26%, P = .02). Our results indicate that DC counts are closely correlated with HSCT outcomes and warrant further prospective evaluation and possible early therapeutic interventions to ameliorate severe aGVHD and decrease mortality.
树突状细胞（DCs）是驱动免疫反应和免疫耐受的抗原呈递细胞，可分为不同亚群：髓样DCs（mDCs：谱系阴性；HLA-DR+，11c+）、浆细胞样树突状细胞（pDCs：HLA-DR+，CD123+）和单核细胞衍生的DCs（moDC：谱系阴性，11c+，16+）。造血干细胞移植（HSCT）后，受者外周血（PB）中DC计数较低与较差的预后相关，但DC移植物含量的相关性仍不清楚，且在无关供体HSCT情况下的数据较少。我们评估了111例HSCT受者（中位年龄17岁；范围1至74岁）PB中的DC移植物含量并监测了DC的恢复情况，这些受者接受了来自无关供体（81%）或相关供体（19%）的骨髓（46%）、脐带血（32%）或PB（22%）。在86例实现持续同种异体造血恢复的患者中，移植后3周时所有DC亚群（pDC、mDC和moDC）计数较高的患者非复发死亡率（NMR）和急性移植物抗宿主病（aGVHD）的发生率较低，生存率更高。pDC计数与更显著的结果相关：pDC计数较高的患者NRM发生率低得多（3%对47%，P <.0001），aGVHD发生率较低（24%对67%，P <.0001），总体生存率更高（92%对45%，P <.0001）。相反，移植物中较高的pDC计数与aGVHD风险增加相关（55%对26%，P =.02）。我们的结果表明，DC计数与HSCT结果密切相关，值得进一步进行前瞻性评估以及可能的早期治疗干预，以改善严重aGVHD并降低死亡率。
