Decline in number of elevated blood CD3+ CD56+ NKT cells in response to intravenous immunoglobulin treatment correlates with successful pregnancy

Decline in number of elevated blood CD3+ CD56+ NKT cells in response to intravenous immunoglobulin treatment correlates with successful pregnancy
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DOI:
10.1111/j.1600-0897.2007.00529.x
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发表时间:
2007-11-01
影响因子:
3.6
通讯作者:
Clark, David A.
Clark, David A.
中科院分区:
医学3区
文献类型:
--
作者:
van den Heuvel, Marianne J.;Peralta, Crystal G.;Clark, David A.

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血液自然杀伤(NK)细胞升高的患者可以接受静脉注射免疫球蛋白(IVIG)治疗,但对血液NK细胞检测的实用性存在争议。人CD 56(+)NK细胞包括几个亚群,其中包括人细胞毒性CD 56(+)CD 16(+)亚群。在妊娠失败的小鼠模型中,NKT细胞似乎很重要。然而,小鼠模型可能只适用于一个子集的患者,因为复发性妊娠失败是一个异质性的group.Method研究伦理学批准的观察性研究进行观察治疗的影响,总的血液淋巴细胞,和亚群的CD 56(+)血液淋巴细胞,包括CD 56(+)CD 3(+)NKT细胞测定流式细胞术,并与妊娠结局。15名有成功妊娠史的育龄妇女和31名患有反复着床失败或反复自然流产的妇女在一个月经周期期间或治疗前和治疗期间提供了连续的血液样本。IVIG后一组给予或不肝素/aspires.Results8 30不孕妇女提出了大量的CD 56(+)CD 3(+)NKT细胞,IVIG治疗后下降。与具有平均NKT细胞数量且无自身免疫证据的女性相比,在研究过程中,伴有或不伴有自身免疫的NKT细胞升高组的成功妊娠率显著更高(P = 0.018)。NKT水平升高是治疗成功的独立预测因子(P = 0.003)。结论IVIG治疗可改善复发性妊娠丢失或种植失败患者NKT细胞水平升高,使妊娠成功。NKT细胞数的测定可能有助于更有可能从IVIG治疗中获益的患者,并值得在随机II期研究中进一步检查。
ProblemPatients with elevated blood natural killer (NK) cells may be offered intravenous immunoglobulin (IVIG) treatment, but there is controversy about the utility of blood NK cell testing. Human CD56(+) NK cells include several subpopulations that include the putatively cytotoxic CD56(+) CD16(+) subset. In mouse models of pregnant failure, NKT cells appear to be important. However, a mouse model may only be pertinent to a subset of patients, as recurrent pregnancy failure is a heterogenous group.Method of studyAn ethics-approved observational study was done to observe the effect of treatment on total blood lymphoid cells, and subsets of CD56(+) blood lymphocytes including CD56(+) CD3(+) NKT cells determined by flow cytometry, and to correlate with pregnancy outcome. Fifteen fertile women with a history of successful pregnancy and thirty-one women suffering from repeated implantation failure or recurrent spontaneous abortion provided serial blood samples during one menstrual cycle or prior to and during treatment. IVIG was administered to the latter group with or without heparin/aspirin.ResultsEight of thirty infertile women presented with high numbers of CD56(+) CD3(+) NKT cells, which declined after treatment with IVIG. The elevated NKT cell group with or without concomitant autoimmunity achieved a significantly higher successful pregnancy rate over the course of the study, as compared to women with average numbers of NKT cells and no evidence of autoimmunity (P = 0.018). Elevated NKT levels alone was an independent predictor of success on treatment (P = 0.003).ConclusionElevated NKT cells in recurrent pregnancy loss or implantation failure can be ameliorated with IVIG treatment, and result in successful pregnancy. Assay of NKT cell numbers may idengif"y patients who are more likely to benefit from IVIG therapy and merits further examination in randomized phase II studies.