用β2糖蛋白免疫PL/J小鼠后诱导实验性抗磷脂抗体综合征

Induction of experimental antiphospholipid antibody syndrome in PL/J mice following immunization with beta 2 GPI.

作者信息

García C O, Kanbour-Shakir A, Tang H, Molina J F, Espinoza L R, Gharavi A E

机构信息

Department of Medicine, Louisiana State University Medical Center, New Orleans 70112-2822, USA.

出版信息

Am J Reprod Immunol. 1997 Jan;37(1):118-24. doi: 10.1111/j.1600-0897.1997.tb00200.x.

DOI:10.1111/j.1600-0897.1997.tb00200.x

PMID:9138445

Abstract

PROBLEM

Immunization with beta 2-glycoprotein I (beta 2 GPI) induces antiphospholipid antibodies (aPL) in normal mice and rabbits. Recently we reported early onset of autoimmunity in MRL/(+2) mice following immunization with beta 2 GPI. There is a close association between aPL with thrombosis, recurrent fetal loss, and intrauterine growth retardation. In this study we evaluated the effect of beta 2 GPI-induced aPL on pregnancy outcomes in an inbred strain of mice (PL/J).

METHOD

Three groups of seven-week female PL/J mice (12 per group) were studied. Group A was immunized with beta 2 GPI and group B with ovalbumin; group C was not not immunized. After two booster injections, the mice were tested for aPL, anti-DNA by ELISA, and for ANA by indirect immunofluorescence. Platelet count and pregnancy outcomes were studied at the age of 14 weeks.

RESULTS

The aPL and anti-DNA levels were higher at 12 and 14 weeks in group A; the optical densities (OD) were 1.72 +/- 0.6 and 0.699 +/- 0.25 for group A, 0.09 +/- 0.040 and 0.230 +/- 0.47 for group B, and 0.0435 +/- 0.003 and 0.119 +/- 0.26 for group C (comparing group A with groups B and C combined, P < 0.001). ANA titers rose in groups A and B by age, but they were significantly higher at 14 weeks in group A. The mean titers were 1/286, 1/90, and 1/16 for A, B, and C, respectively (P < 0.001). The platelet counts were not significantly different among the three groups. The titer size was significantly smaller in group A, as evidenced by the numbers of viable fetuses among the mice that became pregnant in each group: 0.75, 2.45, and 5.5 in groups A, B, and C, respectively. Seven pregnant mice in group A had complete resorption, seven pregnant mice in group B showed focal (partial) resorption areas, by only one mouse in group C had complete resorption of the embryos, as shown by histopathological studies, although the fecundity rate was similar in the three groups.

CONCLUSION

Our data suggest a pathogenic role for beta 2 GPI-induced aPL in the development of experimental models of APS in PL/J mice.

摘要

问题

用β2-糖蛋白I（β2GPI）免疫可在正常小鼠和兔子中诱导抗磷脂抗体（aPL）产生。最近我们报道，用β2GPI免疫MRL/（+2）小鼠后会早期出现自身免疫。aPL与血栓形成、反复流产和宫内生长迟缓密切相关。在本研究中，我们评估了β2GPI诱导的aPL对近交系小鼠（PL/J）妊娠结局的影响。

方法

研究了三组7周龄雌性PL/J小鼠（每组12只）。A组用β2GPI免疫，B组用卵清蛋白免疫；C组未免疫。两次加强注射后，通过ELISA检测小鼠的aPL、抗DNA水平，通过间接免疫荧光检测抗核抗体（ANA）。在14周龄时研究血小板计数和妊娠结局。

结果

A组在12周和14周时aPL和抗DNA水平较高；A组的光密度（OD）分别为1.72±0.6和0.699±0.25，B组为0.09±0.040和0.230±0.47，C组为0.0435±0.003和0.119±0.26（A组与B组和C组合并比较，P<0.001）。A组和B组的ANA滴度随年龄增加，但A组在14周时显著更高。A、B、C组的平均滴度分别为1/286、1/90和1/16（P<0.001）。三组之间的血小板计数无显著差异。A组的胎仔大小显著更小，每组怀孕小鼠中活胎数量可证明：A、B、C组分别为0.75、2.45和5.5。组织病理学研究显示，A组7只怀孕小鼠胚胎完全吸收，B组7只怀孕小鼠有局部（部分）吸收区域，C组只有1只小鼠胚胎完全吸收，尽管三组的受孕率相似。