Pérez Claudio A, Rabanales Ramón, Rojas-Alcayaga Gonzalo, Larrondo Milton, Escobar Alejandro F, López Mercedes N, Salazar-Onfray Flavio, Alfaro Jorge I, González Fermín E
Cell Therapy Laboratory, Blood Bank Service, University of Chile Clinical Hospital, Santiago, Chile.
Department of Oral Pathology and Medicine, Faculty of Dentistry, University of Chile, Santiago, Chile.
J Oral Pathol Med. 2016 Feb;45(2):127-35. doi: 10.1111/jop.12338. Epub 2015 Jun 23.
Graft-versus-host disease (GVHD) is one of the main complications after haematopoietic stem cell transplantation. Clinical features of GVHD include either an acute (aGVHD) or a chronic (cGVHD) condition that affects locations such as the oral mucosa. While the involvement of the host's dendritic cells (DCs) has been demonstrated in aGVHD, the origin (donor/host) and mechanisms underlying oral cGVHD have not been completely elucidated. In this study, we intend to determine the origin of DCs present in mucosal tissue biopsies from the oral cavity of transplanted patients affected by cGVHD.
We purified DCs, from oral biopsies of three patients with cGVHD, through immunobeads and subsequently performed DNA extraction. The origin of the obtained DCs was determined by PCR amplification of 13 informative short tandem repeat (STR) alleles. We also characterised the DCs phenotype and the inflammatory infiltrate from biopsies of two patients by immunohistochemistry.
Clinical and histological features of the biopsies were concordant with oral cGVHD. We identified CD11c-, CD207- and CD1a-positive cells in the epithelium and beneath the basal layer. Purification of DCs from the mucosa of patients affected by post-transplantation cGVHD was >95%. PCR-STR data analysis of DCs DNA showed that 100% of analysed cells were of donor origin in all of the evaluated patients.
Our results demonstrate that resident DCs isolated from the oral tissue of allotransplanted patients affected by cGVHD are originated from the donor. Further research will clarify the role of DCs in the development and/or severity of oral cGVHD.
移植物抗宿主病(GVHD)是造血干细胞移植后的主要并发症之一。GVHD的临床特征包括急性(aGVHD)或慢性(cGVHD)病症,可累及口腔黏膜等部位。虽然已证实在aGVHD中宿主树突状细胞(DCs)参与其中,但口腔cGVHD的起源(供体/宿主)及其潜在机制尚未完全阐明。在本研究中,我们旨在确定受cGVHD影响的移植患者口腔黏膜组织活检中存在的DCs的起源。
我们通过免疫磁珠从3例cGVHD患者的口腔活检组织中纯化DCs,随后进行DNA提取。通过对13个信息性短串联重复序列(STR)等位基因进行PCR扩增来确定所得DCs的起源。我们还通过免疫组织化学对2例患者活检组织中的DCs表型和炎性浸润进行了表征。
活检组织的临床和组织学特征与口腔cGVHD一致。我们在上皮层和基底层下方鉴定出CD11c、CD207和CD1a阳性细胞。从移植后cGVHD患者的黏膜中纯化DCs的纯度>95%。对DCs DNA的PCR-STR数据分析表明,在所有评估患者中,100%的分析细胞来源于供体。
我们的结果表明,从受cGVHD影响的同种异体移植患者口腔组织中分离出的驻留DCs来源于供体。进一步的研究将阐明DCs在口腔cGVHD发生和/或严重程度中的作用。