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Abstract：
OBJECTIVE: Maternal immune responses are altered during pregnancy and differ between nulliparous and multiparous women. The influence of a prior gestation on autophagy in peripheral blood mononuclear cells (PBMCs) from pregnant women has not been determined and is the subject of this investigation.
METHODS: Peripheral blood mononuclear cells were isolated from 212 pregnant women and immediately lysed in the presence of protease inhibitors, and the extent of autophagy was determined by quantitation of the concentration of p62 (sequestosome-1) in the lysates by enzyme-linked immunosorbent assay (ELISA). In PBMCs, the p62 level is inversely related to the extent of autophagy. The level of the stress-inducible 70-kDa heat shock protein (hsp70), an inhibitor of autophagy, was also measured in the lysates by ELISA. Data were analyzed by the Spearman rank correlation, Mann-Whitney U test, or Kruskal-Wallis test, as appropriate.
RESULTS: The p62 concentration in PBMCs increased (autophagy decreased) with the number of previous live ( P = .0322), preterm ( P = .0143), or term ( P = .0418) deliveries. The p62 level was lower (autophagy higher) in women with a prior spontaneous pregnancy loss but no deliveries as compared to women with their first conception ( P = .0087). The intracellular hsp70 concentration correlated with the p62 level ( P < .0001).
CONCLUSIONS: Multiparity is associated with a reduced level of autophagy in PBMCs. Dysregulated autophagy might be one mechanism leading to spontaneous abortion in nulliparous women.
METHODS: Peripheral blood mononuclear cells were isolated from 212 pregnant women and immediately lysed in the presence of protease inhibitors, and the extent of autophagy was determined by quantitation of the concentration of p62 (sequestosome-1) in the lysates by enzyme-linked immunosorbent assay (ELISA). In PBMCs, the p62 level is inversely related to the extent of autophagy. The level of the stress-inducible 70-kDa heat shock protein (hsp70), an inhibitor of autophagy, was also measured in the lysates by ELISA. Data were analyzed by the Spearman rank correlation, Mann-Whitney U test, or Kruskal-Wallis test, as appropriate.
RESULTS: The p62 concentration in PBMCs increased (autophagy decreased) with the number of previous live ( P = .0322), preterm ( P = .0143), or term ( P = .0418) deliveries. The p62 level was lower (autophagy higher) in women with a prior spontaneous pregnancy loss but no deliveries as compared to women with their first conception ( P = .0087). The intracellular hsp70 concentration correlated with the p62 level ( P < .0001).
CONCLUSIONS: Multiparity is associated with a reduced level of autophagy in PBMCs. Dysregulated autophagy might be one mechanism leading to spontaneous abortion in nulliparous women.
摘要：
目的：孕妇的免疫反应在怀孕期间发生了改变，在未产和多产妇女之间存在差异。尚未确定先前妊娠对孕妇外周血单核细胞（PBMC）中自噬的影响，并且是本研究的主题。
方法：从212名孕妇中分离出外周血单核细胞，并在蛋白酶抑制剂存在下立即裂解，通过酶联免疫吸附测定（ELISA）定量裂解物中p62（螯合体-1）的浓度来确定自噬的程度。在PBMC中,p62水平与自噬程度呈负相关。应激诱导的70kDa热休克蛋白（hsp70）的水平，自噬的抑制剂，还通过ELISA在裂解物中测量。数据采用Spearman秩相关分析，Mann-WhitneyU测试,或者Kruskal-Wallis测试,视情况而定。
结果：PBMC中的p62浓度随着先前存活的数量而增加（自噬减少）（P=.0322），早产（P=.0143），或期限（P=0.0418）交付。与首次受孕的女性相比，先前自发妊娠丢失但未分娩的女性的p62水平较低（自噬较高）（P=.0087）。细胞内hsp70浓度与p62水平相关(P<0.0001)。
结论：多重奇偶校验与PBMC中自噬水平降低相关。自噬失调可能是导致未产妇女自然流产的机制之一。
方法：从212名孕妇中分离出外周血单核细胞，并在蛋白酶抑制剂存在下立即裂解，通过酶联免疫吸附测定（ELISA）定量裂解物中p62（螯合体-1）的浓度来确定自噬的程度。在PBMC中,p62水平与自噬程度呈负相关。应激诱导的70kDa热休克蛋白（hsp70）的水平，自噬的抑制剂，还通过ELISA在裂解物中测量。数据采用Spearman秩相关分析，Mann-WhitneyU测试,或者Kruskal-Wallis测试,视情况而定。
结果：PBMC中的p62浓度随着先前存活的数量而增加（自噬减少）（P=.0322），早产（P=.0143），或期限（P=0.0418）交付。与首次受孕的女性相比，先前自发妊娠丢失但未分娩的女性的p62水平较低（自噬较高）（P=.0087）。细胞内hsp70浓度与p62水平相关(P<0.0001)。
结论：多重奇偶校验与PBMC中自噬水平降低相关。自噬失调可能是导致未产妇女自然流产的机制之一。
