Elevated soluble human leukocyte antigen G levels in patients after allogeneic stem cell transplantation are associated with less severe acute and chronic graft-versus-host disease
Elevated soluble human leukocyte antigen G levels in patients after allogeneic stem cell transplantation are associated with less severe acute and chronic graft-versus-host disease
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DOI：
10.1038/s41409-018-0145-1
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发表时间：
2018-09-01
影响因子：
4.8
通讯作者：
Rebmann, Vera
中科院分区：
文献类型：
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作者：
Kordelas, Lambros;Nardi, Fabiola da Silva;Rebmann, Vera
HLA-G是一种非经典的I类分子，其通过抑制细胞毒性NK和CD 8 + T细胞以及通过诱导调节性T细胞来诱导同种异体情况下的耐受性。一致地，在实体器官移植中，HLA-G与急性和慢性排斥反应的较低风险相关，而其在异基因干细胞移植（allo-SCT）中的作用较少确定。我们在此对异基因造血干细胞移植后患者的HLA-G水平进行了详细分析，结果显示可溶性HLA-G（sHLA-G）水平升高与急性（p = 0.06）和慢性（p = 0.0025）GvHD不严重以及总生存率上级（p = 0.03）相关。可溶性HLA-G水平也与体内调节性T细胞的频率正相关。这些临床数据得到体外分析的证实，显示患者来源的sHLA-G抑制同种异体免疫应答。患者的ATG治疗主要影响allo-SCT后的sHLA-G水平。因此，本研究强调了sHLA-G水平升高与不太严重的急性和慢性GvHD的相关性，并提供了额外的功能分析，阐明了allo-SCT背景下sHLA-G可能的耐受诱导机制。
HLA-G is a non-classical class I molecule which induces tolerance in allogeneic situations by inhibition of cytotoxic NK and CD8 + T cells and by induction of regulatory T cells. Concordantly, in solid organ transplantation HLA-G is associated with a lower risk for acute and chronic rejection, whereas its role in allogeneic stem cell transplantation (allo-SCT) is less established. We here present detailed analyses of HLA-G-levels in patients after allo-SCT showing a correlation of elevated soluble HLA-G (sHLA-G) levels with less severe acute (p = 0.06) and chronic GvHD (p = 0.0025) and with a superior overall survival (p = 0.03). Soluble HLA-G levels are also positively correlated with the frequency of regulatory T cells in vivo. These clinical data are corroborated by in vitro analyses showing that patients-derived sHLA-G inhibit allogeneic immune responses. ATG-treatment of patients dominantly affects the sHLA-G levels post allo-SCT. Thus, this study highlights the association of elevated sHLA-G levels with less severe acute and chronic GvHD and provides additional functional analyses elucidating possible tolerance-inducing mechanisms of sHLA-G in the context of allo-SCT.