Induction of antiphospholipid antibodies and antiphospholipid syndrome-like autoimmunity in naive mice with antibody against human parvovirus B19 VP1 unique region protein.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Tzang
Bor-Show
BS
Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan, ROC.
Lee
Yi-Ju
YJ
Yang
Tzi-Peng
TP
Tsay
Gregory J
GJ
Shi
Jing-Yu
JY
Tsai
Chun-Chou
CC
Hsu
Tsai-Ching
TC
D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000276:immunology* / Q000378:metabolism; D000917:Antibody Formation; D000918:Antibody Specificity / Q000276:immunology*; D016736:Antiphospholipid Syndrome / Q000276:immunology* / Q000821:virology; D001323:Autoantibodies; D015551:Autoimmunity / Q000276:immunology*; D036022:Capsid Proteins / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D016732:Parvovirus B19, Human / Q000276:immunology*; D011817:Rabbits
D017152:Antibodies, Antiphospholipid; D001323:Autoantibodies; D036022:Capsid Proteins; C095547:capsid protein VP1, parvovirus B19