La Rosa L, Meroni P L, Tincani A, Balestrieri G, Faden D, Lojacono A, Morassi L, Brocchi E, Del Papa N, Gharavi A
Istituto di Medicina Interna, Malattie Infettive & Immunopatologia, University of Milan, Italy.
J Rheumatol. 1994 Sep;21(9):1684-93.
To investigate the immunohistological distribution of beta 2-glycoprotein I (beta 2 GPI) and placental anticoagulant protein I (PAP-I) in normal and pathological placentae of patients with antiphospholipid (aPL) antibody associated recurrent fetal loss. These proteins are 2 natural anticoagulants able to interfere with aPL antibody binding.
Placentae from 4 patients with primary antiphospholipid antibody syndrome (pAPS), from 2 patients with aPL negative systemic lupus erythematosus (SLE) and from 7 healthy women were studied. Cryostatic placental sections were tested by indirect immunofluorescence using polyclonal anti-PAP-I and anti-beta 2GPI antisera as well as purified IgG and anti-beta 2GPI monoclonal antibody. The same tissue sections were also tested by direct immunofluorescence with FITC-F(ab)2 goat antihuman IgG.
We found that (a) the placental distribution of PAP-I was comparable in normal and pathological specimens; (b) on the contrary, increased beta 2GPI deposition was present on the trophoblast surfaces of placentae obtained from patients with persistent raised titers of aPL antibodies. Comparable IgG deposition on villi surface was also found in aPL positive but not in control placentae.
Our data are consistent with the hypothesis that high titer aPL binds to a beta 2GPI phospholipid complex in placentae of women with recurrent fetal loss but that a quantitative deficiency of PAP-I does not play a pathogenetic role in aPL associated fetal loss.
研究β2-糖蛋白I(β2GPI)和胎盘抗凝蛋白I(PAP-I)在抗磷脂(aPL)抗体相关复发性流产患者正常和病理胎盘组织中的免疫组织学分布。这两种蛋白是能够干扰aPL抗体结合的天然抗凝剂。
研究了4例原发性抗磷脂抗体综合征(pAPS)患者、2例aPL阴性系统性红斑狼疮(SLE)患者以及7例健康女性的胎盘组织。使用多克隆抗PAP-I和抗β2GPI抗血清以及纯化的IgG和抗β2GPI单克隆抗体,通过间接免疫荧光检测冰冻胎盘切片。同一组织切片还用异硫氰酸荧光素(FITC)-F(ab)2山羊抗人IgG进行直接免疫荧光检测。
我们发现:(a)正常和病理标本中PAP-I的胎盘分布相当;(b)相反,在aPL抗体滴度持续升高的患者胎盘滋养层表面,β2GPI沉积增加。在aPL阳性胎盘绒毛表面也发现了类似的IgG沉积,而对照胎盘则未发现。
我们的数据支持以下假设,即高滴度aPL与复发性流产女性胎盘中的β2GPI磷脂复合物结合,但PAP-I的定量缺乏在aPL相关的流产中不发挥致病作用。