Autoantibody response and pregnancy-related pathology induced by combined LPS and tetanus toxoid hyperimmunization in BALB/c and C57BL/6 mice

Abstract

Recent data concerning antiphospholipid syndrome (APS) induction have shown that β₂-glycoprotein I (β₂GPI) binds lipopolysaccharide (LPS), which results in conformational changes, exposition of a cryptic epitope and possible pathological anti-β₂GPI antibody production. In order to investigate the effects of LPS on the induction of APS-related pathology, we performed hyperimmunization of BALB/c and C57BL/6 mice with LPS, alone or in combination with tetanus toxoid (TTd), a protein structurally similar to β₂GPI. We report that, although high affinity pathological anti-β₂GPI antibodies were produced in all groups of animals, the reproductive pathology was recorded only in mice that received both LPS and TTd, implying on the important roles of both infections and molecular mimicry in APS pathogenesis. Moreover, APS-related reproductive pathology was more pronounced in BALB/c (lowered fertility and fecundity) than C57BL/6 mice (lowered fecundity), which correlated well with the disruption in natural antibody network observed in BALB/c mouse strain.

• β₂-glycoprotein I
• antiphospholipid syndrome
• fertility
• molecular mimicry
• natural antibodies

Acknowledgements

The authors would like to thank Dr. Slađana Andrejević (Clinical Center of Serbia, Institute of Allergology and Immunology, Belgrade) for providing the sera of APS patients, and Ivan Gaković and Svetlana Kostić (Institute of Virology, Vaccines and Sera Torlak, Belgrade) for their dedication and help in intravenous immunization experiments described in this article.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. This work was supported by Ministry of Education, Science and Technological Development of the Republic of Serbia (grant numbers 172049 and 41021).