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患有自身免疫性风湿疾病的孕妇体内的可溶性人类白细胞抗原-G

Soluble HLA-G in pregnancies complicated by autoimmune rheumatic diseases.

作者信息

Beneventi Fausta, Badulli Carla, Locatelli Elena, Caporali Roberto, Ramoni Véronique, Cavagnoli Chiara, Simonetta Margherita, Garbin Giulia, Tinelli Carmine, Alpini Claudia, Montecucco CarloMaurizio, Martinetti Miryam, Spinillo Arsenio

机构信息

Department of Obstetrics and Gynecology, IRCCS Foundation Policlinico San Matteo and University of Pavia, Pavia, Italy.

Immunogenetics Laboratory, Immunohematology and Transfusion Center, IRCCS Foundation Policlinico San Matteo, Pavia, Italy.

出版信息

J Reprod Immunol. 2015 Aug;110:67-73. doi: 10.1016/j.jri.2015.04.005. Epub 2015 May 21.

Abstract

Autoimmune rheumatic diseases in pregnancies are associated with increased adverse obstetric outcomes. We compared maternal soluble human leucocyte antigen-G (sHLA-G) blood levels in subjects with a rheumatic disease preexisting pregnancy and unaffected controls. Third-trimester blood maternal sHLA-G concentrations were significantly higher in subjects with rheumatic diseases than in controls (mean 93.1ng/ml [SD 42.1] vs 58.1ng/ml [SD 96.3], p=0.003). Cord blood sHLA-G concentrations were significantly higher in rheumatic disease than in those born to control mothers (median 41.2ng/ml [IQR: 3.3-44.0] vs 17.9ng/ml [IQR: 17.2-88.1], p=0.007). A strict positive correlation (r=0.88, p<0.001) was found between the maternal and fetal titers of ANA autoantibodies as well as between maternal and fetal sHLAG circulating levels (r=0.58 and r=0.67, respectively, for controls and cases, p<0.001). Maternal s-HLA-G blood concentrations were significantly higher in subjects with rheumatic disease DEL/DEL homozygous for a polymorphism of the 3' untranslated regulatory region of HLA-G (HLA-G 14bp) than in the corresponding healthy controls (mean values 141.5ng/ml [SD: 166] vs 54.2ng/ml [SD: 35], p=0.009). Increasing maternal and cord blood levels of s-HLA-G concentrations among pregnant subjects with rheumatic diseases compared with controls suggest that autoimmune diseases prompt a maternal and fetal immune response that favors pregnancy immune tolerance.

摘要

妊娠期间的自身免疫性风湿性疾病与不良产科结局增加有关。我们比较了妊娠前患有风湿性疾病的受试者和未受影响的对照组的母体可溶性人类白细胞抗原-G(sHLA-G)血液水平。患有风湿性疾病的受试者在妊娠晚期的母体sHLA-G浓度显著高于对照组(平均值93.1ng/ml[标准差42.1] vs 58.1ng/ml[标准差96.3],p=0.003)。患有风湿性疾病的受试者的脐血sHLA-G浓度显著高于对照组母亲所生婴儿(中位数41.2ng/ml[四分位间距:3.3-44.0] vs 17.9ng/ml[四分位间距:17.2-88.1],p=0.007)。在抗核抗体(ANA)自身抗体的母体和胎儿滴度之间以及母体和胎儿sHLAG循环水平之间发现了严格的正相关(r=0.88,p<0.001)(对照组和病例组的r分别为0.58和0.67,p<0.001)。对于HLA-G 3'非翻译调控区多态性(HLA-G 14bp)为DEL/DEL纯合子的风湿性疾病受试者,其母体s-HLA-G血液浓度显著高于相应的健康对照组(平均值141.5ng/ml[标准差:166] vs 54.2ng/ml[标准差:35],p=0.009)。与对照组相比,患有风湿性疾病的孕妇母体和脐血中s-HLA-G浓度升高,这表明自身免疫性疾病引发了有利于妊娠免疫耐受的母体和胎儿免疫反应。

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