Tzang Bor-Show, Lee Yi-Ju, Yang Tzi-Peng, Tsay Gregory J, Shi Jing-Yu, Tsai Chun-Chou, Hsu Tsai-Ching
Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan, ROC.
Clin Chim Acta. 2007 Jul;382(1-2):31-6. doi: 10.1016/j.cca.2007.03.014. Epub 2007 Mar 24.
Previous studies have postulated a connection between human parvovirus B19 (B19) infection and anti-phospholipid antibodies (APhL). B19 infection and anti-phospholipid syndrome (APS) exhibit congruent symptoms. Recently, phospholipase A2 (PLA2)-like activity has been linked to the VP1 unique region (VP1u) of B19. However, the precise role of B19-VP1u in pathogenesis of autoimmunity is still obscure.
To elucidate the roles of VP1u in B19 infection and autoimmunity, the reactivity of B19-VP1u proteins with various autoantibodies were evaluated by ELISA and immunoblotting. Rabbits were immunized with purified recombinant B19-VP1u protein to generate anti-sera. Absorption experiments were conducted to determine the binding specificity of rabbit anti-sera against B19-VP1u, cardiolipin (CL) and beta-2-glycoprotein I (beta2GPI). Moreover, the effects of passive transfer of polyclonal rabbit anti-B19-VP1u IgG antibodies on platelets, activated partial thromboplastin time (aPTT), and autoantibodies were assessed.
Autoantibodies against CL, beta2GPI, and phospholipid (PhL) in sera from patients with B19 infection, were cross-reactive with B19-VP1u. Consistently, sera from rabbits immunized with recombinant B19-VP1u protein displayed raised detectable immunoglobulins against B19-VP1u, CL, beta2GPI and PhL. Additionally, the mice immunized with anti-B19-VP1u IgG developed thrombocytopenia, prolongation of aPTT, and autoantibody against beta2GPI and PhL.
These experimental results suggested the association between B19-VP1u and production of anti-beta2GPI antibodies, APhL, and APS-like autoimmunity. Altogether, it may provide a clue in understanding the role of B19-VP1u in inducing autoantibodies and B19-associated APS manifestations.
既往研究推测人细小病毒B19（B19）感染与抗磷脂抗体（APhL）之间存在联系。B19感染与抗磷脂综合征（APS）表现出相似的症状。最近，磷脂酶A2（PLA2）样活性已与B19的VP1独特区域（VP1u）相关联。然而，B19-VP1u在自身免疫发病机制中的精确作用仍不清楚。
为阐明VP1u在B19感染和自身免疫中的作用，通过酶联免疫吸附测定（ELISA）和免疫印迹法评估B19-VP1u蛋白与各种自身抗体的反应性。用纯化的重组B19-VP1u蛋白免疫兔子以产生抗血清。进行吸收实验以确定兔抗血清对B19-VP1u、心磷脂（CL）和β2糖蛋白I（β2GPI）的结合特异性。此外，评估了多克隆兔抗B19-VP1u IgG抗体被动转移对血小板、活化部分凝血活酶时间（aPTT）和自身抗体的影响。
B19感染患者血清中针对CL、β2GPI和磷脂（PhL）的自身抗体与B19-VP1u发生交叉反应。同样，用重组B19-VP1u蛋白免疫的兔子血清显示出针对B19-VP1u、CL、β2GPI和PhL的可检测免疫球蛋白升高。此外，用抗B19-VP1u IgG免疫的小鼠出现血小板减少、aPTT延长以及针对β2GPI和PhL的自身抗体。
这些实验结果提示B19-VP1u与抗β2GPI抗体、APhL和APS样自身免疫的产生之间存在关联。总之，这可能为理解B19-VP1u在诱导自身抗体和B19相关APS表现中的作用提供线索。
