重度子痫前期PIBF的表达及其与免疫耐受失衡的关系
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摘要
目的探讨重度子痫前期胎盘及外周血孕酮诱导封闭因子(PIBF)表达情况及其与免疫耐受失衡的关系。方法选取2012年1月~12月期间早发型重度子痫前期(EOPE)25例,晚发型重度子痫前期(LOPE)22例,对照组25例,收集产前外周血与产后胎盘。用免疫组织化学(SABC法)检测胎盘PIBF的表达及定位,ELISA试剂盒检测血清PIBF水平,流式细胞仪检测外周血中Th1和Th2细胞百分率,计算Th1/Th2比值。结果胎盘PIBF表达于蜕膜组织、合体滋养层细胞和部分绒毛滋养层细胞。血清PIBF水平在EOPE组为213.58±44.93 ng/ml,LOPE组为243.00±61.19 ng/ml,对照组为273.91±48.57 ng/ml。三组间血清PIBF含量、Th1/Th2比值和胎盘PIBF-IOD值差异均有统计学意义(P<0.05)。EOPE组和对照组相比,血清PIBF降低、胎盘PIBF表达量(PIBF-IOD)减少、外周血Th1/Th2比值增高(P<0.05)。重度子痫前期孕妇血清PIBF与胎盘PIBF-IOD呈正相关关系,与外周血Th1/Th2呈负相关关系(P<0.05)。但只有EOPE组血清PIBF与24h尿蛋白定量呈负相关关系(P<0.05)。结论 PIBF介导的免疫耐受失衡可能参与重度子痫前期发病机制。PIBF是妊娠诱发淋巴细胞分泌的免疫调节抑制因子及重度子痫前期的保护因素,有望成为新的治疗靶点。
Objective To explore progesterone- induced blocking factor(PIBF) expression in the placenta and blood of patients with severe preeclampsia and its relationship with immune tolerance imbalance. Methods Forty- seven patients admitted between January and December, 2012 were enrolled in this study, including 25 patients with early- onset severe preeclampsia(EOPE) and 22 with late-onset severe preeclampsia(LOPE), with 25 women with normal pregnancy serving as control group.The antenatal blood and postpartum placenta were collected for immunohistochemical staining to detect PIBF expression in the placenta and for testing serum PIBF level using ELISA. Flow cytometry was used to detect the percentage of circulating Th1 and Th2 cells and the Th1/Th2 ratio was calculated. Results PIBF was expressed in decidual cells, syncytiotrophoblasts and partial cytotrophablasts. The serum PIBF levels were 213.58 ± 44.93 ng/ml in EOPE group, 243.00 ± 61.19 ng/ml in LOPE group and 273.91±48.57 ng/ml in control group. There were significant differences in serum PIBF, blood Th1/Th2 and placenta PIBF-IOD among the 3 groups(P<0.05). EOPE group had significantly lower serum PIBF, lower llacental PIBF quantity(PIBFIOD) and higher blood Th1/Th2 than the control group(P<0.05). Serum PIBF in women with severe preeclampsia was positively correlated with placenta PIBF- IOD and negatively with blood Th1/Th2 ratio(P<0.05), but a negative correlation between serum PIBF and 24-hour urinary protein was found only in EOPE group(P<0.05). Conclusion The immune tolerance imbalance mediated by PIBF may participate in the pathogenesis of severe preeclampsia. PIBF, the immune suppressor secreted by lymphocytes of pregnancy women, is also a protective factor against severe preeclampsia, which is expected to be a new target in therapy.
Objective To explore progesterone- induced blocking factor(PIBF) expression in the placenta and blood of patients with severe preeclampsia and its relationship with immune tolerance imbalance. Methods Forty- seven patients admitted between January and December, 2012 were enrolled in this study, including 25 patients with early- onset severe preeclampsia(EOPE) and 22 with late-onset severe preeclampsia(LOPE), with 25 women with normal pregnancy serving as control group.The antenatal blood and postpartum placenta were collected for immunohistochemical staining to detect PIBF expression in the placenta and for testing serum PIBF level using ELISA. Flow cytometry was used to detect the percentage of circulating Th1 and Th2 cells and the Th1/Th2 ratio was calculated. Results PIBF was expressed in decidual cells, syncytiotrophoblasts and partial cytotrophablasts. The serum PIBF levels were 213.58 ± 44.93 ng/ml in EOPE group, 243.00 ± 61.19 ng/ml in LOPE group and 273.91±48.57 ng/ml in control group. There were significant differences in serum PIBF, blood Th1/Th2 and placenta PIBF-IOD among the 3 groups(P<0.05). EOPE group had significantly lower serum PIBF, lower llacental PIBF quantity(PIBFIOD) and higher blood Th1/Th2 than the control group(P<0.05). Serum PIBF in women with severe preeclampsia was positively correlated with placenta PIBF- IOD and negatively with blood Th1/Th2 ratio(P<0.05), but a negative correlation between serum PIBF and 24-hour urinary protein was found only in EOPE group(P<0.05). Conclusion The immune tolerance imbalance mediated by PIBF may participate in the pathogenesis of severe preeclampsia. PIBF, the immune suppressor secreted by lymphocytes of pregnancy women, is also a protective factor against severe preeclampsia, which is expected to be a new target in therapy.
引文
[1]Ermisch C,Markert UR.PIBF-Progesterone-Induced blocking factor[J].Z Geburtshilfe Neonatol,2011,215(3):93-7.
[2]Perez-Sepulveda A,Torres MJ,Khoury M,et al.Innate immune system and preeclampsia[J].Front Immunol,2014,5(5):244.
[3]Szekeres-Bartho J,Falkay G.The mechanism of the inhibitory effect of progesterone on lymphocyte cytotoxicity:I.Relationship between cytotoxicity and the cyclooxygenase pathway of arachidonic acid metabolism[J].Am J Reprod Immunol Microbiol,1985,9(1):15-8.
[4]Wu S,Zhang H,Tian J,et al.Expression of kisspeptin/GPR54 and PIBF/PR in the first trimester trophoblast and decidua of women with recurrent spontaneous abortion[J].Pathol Res Pract,2014,210(1):47-54.
[5]Beta J,Szekeres-Bartho J,Skyfta E,et al.Maternal serum progesterone-induced blocking factor at 11-13 weeks'gestation in spontaneous early preterm delivery[J].Fetal Diagn Ther,2011,29(3):197-200.
[6]Szekeres-Bartho J,Polgar BP.The double edged sword.pregnancy and tumor[J].Am J Reprod Immunol,2010,64(2):77-86.
[7]HudiI,FatusiZ,Szekeres-Bartho J,et al.Progesterone-induced blocking factor and cytokine profile in women with threatened preterm delivery[J].Am J Reprod Immunol,2009,61(5):330-7.
[8]Polgar B,Nagy E,Miko F,et al.Urinary progesterone-induced blocking factor concentration is related to pregnancy outcome[J].Biol Reprod,2004,71(5):1699-705.
[9]HudiI,FatusiZ.Progesterone-induced blocking factor(PIBF)and Th(1)/Th(2)cytokine in women with threatened spontaneous abortion[J].J Perinat Med,2009,37(4):338-42.
[10]Homer CS,Brown MA,Mangos G,et al.Non-proteinuric preeclampsia:a novel risk indicator in women with gestational hypertension[J].J Hypertens,2008,26(2):295-302.
[11]Anderle C,Hammer A,Polgár B,et al.Human trophoblast cells Express the immunomodulator progesterone-induced blocking factor[J].J Reprod Immunol,2008,79(1):26-36.
[12]Polgar B,Kispal G,Lachmann M,et al.Molecular cloning and immunologic characterization of a novel c DNA coding for progesterone-induced blocking factor[J].J Immunol,2003,171(11):5956-63.
[13]Miko E,Halasz M,Jericevic-Mulac B,et al.Progesterone-induced blocking factor(PIBF)and trophoblast invasiveness[J].J Reprod Immunol,2011,90(1):50-7.
[14]Halasz M,Polgar B,Berta G,et al.Progesterone-induced blocking factor differentially regulates trophoblast and tumor invasion by altering matrix metalloproteinase activity[J].Cell Mol Life Sci,2013,70(23):4617-30.
[15]Saito S,Nakashima A,Shima T,et al.Th1/Th2/Th17 and regulatory T-cell paradigm in pregnancy[J].Am J Reprod Immunol,2010,63(6):601-10.
[16]Raghupathy R,Al-Mutawa E,Al-Azemi M,et al.Progesteroneinduced blocking factor(PIBF)modulates cytokine production by lymphocytes from women with recurrent miscarriage or preterm delivery[J].J Reprod Immunol,2009,80(2):91-9.
[17]HudiI,Szekeres-Bartho J,FatuiZ,et al.Dydrogesterone supplementation in women with threatened preterm delivery--the impact on cytokine profile,hormone profile,and progesteroneinduced blocking factor[J].J Reprod Immunol,2011,92(1/2):103-7.
[2]Perez-Sepulveda A,Torres MJ,Khoury M,et al.Innate immune system and preeclampsia[J].Front Immunol,2014,5(5):244.
[3]Szekeres-Bartho J,Falkay G.The mechanism of the inhibitory effect of progesterone on lymphocyte cytotoxicity:I.Relationship between cytotoxicity and the cyclooxygenase pathway of arachidonic acid metabolism[J].Am J Reprod Immunol Microbiol,1985,9(1):15-8.
[4]Wu S,Zhang H,Tian J,et al.Expression of kisspeptin/GPR54 and PIBF/PR in the first trimester trophoblast and decidua of women with recurrent spontaneous abortion[J].Pathol Res Pract,2014,210(1):47-54.
[5]Beta J,Szekeres-Bartho J,Skyfta E,et al.Maternal serum progesterone-induced blocking factor at 11-13 weeks'gestation in spontaneous early preterm delivery[J].Fetal Diagn Ther,2011,29(3):197-200.
[6]Szekeres-Bartho J,Polgar BP.The double edged sword.pregnancy and tumor[J].Am J Reprod Immunol,2010,64(2):77-86.
[7]HudiI,FatusiZ,Szekeres-Bartho J,et al.Progesterone-induced blocking factor and cytokine profile in women with threatened preterm delivery[J].Am J Reprod Immunol,2009,61(5):330-7.
[8]Polgar B,Nagy E,Miko F,et al.Urinary progesterone-induced blocking factor concentration is related to pregnancy outcome[J].Biol Reprod,2004,71(5):1699-705.
[9]HudiI,FatusiZ.Progesterone-induced blocking factor(PIBF)and Th(1)/Th(2)cytokine in women with threatened spontaneous abortion[J].J Perinat Med,2009,37(4):338-42.
[10]Homer CS,Brown MA,Mangos G,et al.Non-proteinuric preeclampsia:a novel risk indicator in women with gestational hypertension[J].J Hypertens,2008,26(2):295-302.
[11]Anderle C,Hammer A,Polgár B,et al.Human trophoblast cells Express the immunomodulator progesterone-induced blocking factor[J].J Reprod Immunol,2008,79(1):26-36.
[12]Polgar B,Kispal G,Lachmann M,et al.Molecular cloning and immunologic characterization of a novel c DNA coding for progesterone-induced blocking factor[J].J Immunol,2003,171(11):5956-63.
[13]Miko E,Halasz M,Jericevic-Mulac B,et al.Progesterone-induced blocking factor(PIBF)and trophoblast invasiveness[J].J Reprod Immunol,2011,90(1):50-7.
[14]Halasz M,Polgar B,Berta G,et al.Progesterone-induced blocking factor differentially regulates trophoblast and tumor invasion by altering matrix metalloproteinase activity[J].Cell Mol Life Sci,2013,70(23):4617-30.
[15]Saito S,Nakashima A,Shima T,et al.Th1/Th2/Th17 and regulatory T-cell paradigm in pregnancy[J].Am J Reprod Immunol,2010,63(6):601-10.
[16]Raghupathy R,Al-Mutawa E,Al-Azemi M,et al.Progesteroneinduced blocking factor(PIBF)modulates cytokine production by lymphocytes from women with recurrent miscarriage or preterm delivery[J].J Reprod Immunol,2009,80(2):91-9.
[17]HudiI,Szekeres-Bartho J,FatuiZ,et al.Dydrogesterone supplementation in women with threatened preterm delivery--the impact on cytokine profile,hormone profile,and progesteroneinduced blocking factor[J].J Reprod Immunol,2011,92(1/2):103-7.