Immunomonitoring of graft-versus-host minor histocompatibility antigen correlates with graft-versus-host disease and absence of relapse after graft
Immunomonitoring of graft-versus-host minor histocompatibility antigen correlates with graft-versus-host disease and absence of relapse after graft
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DOI：
10.1111/j.1537-2995.2009.02440.x
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发表时间：
2010-02-01
期刊：
影响因子：
2.9
通讯作者：
Garban, Frederic
中科院分区：
文献类型：
--
作者：
Laurin, David;Hannani, Dalil;Garban, Frederic
背景：在人类白细胞抗原相合的造血干细胞移植后，次要组织相容(MH)抗原同种反应性在移植物抗宿主病(GVHD)和移植物抗白血病(GVL)的发生中起主导作用。研究设计和方法：我们分析了24对供受者在2年的随访期间的mH同种反应性(用于干扰素-γ检测的酶联免疫点[ELISpot])，并将这种同种反应性与移植物抗宿主病(GVHD)的发生或无复发相关。结果：ELISpot干扰素-伽玛试验显示，供者与受者或供者与不匹配的识别的MH抗原在前3个月的同种异体反应与急性GVHD和GVL效应有关。此外，我们还证明，在第三个月后观察到的供受者反应与慢性移植物抗宿主病和移植物抗宿主病高度相关(p=0.0007)。结论：我们的结果为监测MH抗原移植物抗宿主反应提供了一种可靠的方法，并提示目前鉴定的MH对GVHD和GVL有预测价值。
BACKGROUND: After HLA-identical hematopoietic stem cell transplantation, minor histocompatibility (mH) antigen alloreactivity plays a dominant role in the development of graft-versus-host disease (GVHD) and graft versus leukemia (GVL).STUDY DESIGN AND METHODS: We have analyzed the mH alloreactivity (enzyme-linked immunospot [ELISpot] for interferon-gamma [IFN-gamma] assay) from 24 donor/recipient pairs over a period of 2 years of follow-up and correlated such alloreactivity with the development of GVHD or absence of relapse. Circulating specific T cells anti-mH with multimer HLA-peptides were also studied.RESULTS: We show by ELISpot IFN-gamma assay that alloreactivity during the first 3 months from donor versus recipient or donor versus mismatched identified mH antigens is associated with acute GVHD and GVL effect. In addition, we demonstrate that the donor-versus-recipient reactivity observed after the third month is highly associated with chronic GVHD and GVL (p = 0.0007). Finally, we show by multimer HLA-peptide assay that mH epitope-specific T cells present after 3 months are statistically related to the GVL effect.CONCLUSIONS: Our results provide a robust method to monitor mH antigen graft-versus-host reaction and suggest that current identified mH have predictive value on GVHD and GVL.