INDUCTION OF IMMUNOLOGICAL ORAL TOLERANCE IN ANTIPHOSPHOLIPID SYNDROME: AN ANIMAL MODEL
- Asaf Shemer, Israel
Abstract
Background and Aims
It is well established that the humoral immunity in antiphospholipid syndrome (APS) is presented by circulating pathogenic anti-β2GPI autoantibodies. These antibodies play a major role in the disease pathogenesis by targeting mainly domain I of the β2GPI protein. In the current trial, we had orally administered a domain-I derivative of the β2GPI molecule, in order to evaluate a new therapeutic approach: induction of oral tolerance in a mouse model of APS.
Methods
BALB/c mice immunized with β2GPI, were fed with either domain-I, domain-V or complete β2GPI molecule.
Results
β2GPI immunized mice developed experimental APS which were fed with domain-I significantly had decreased fetal loss (p<0.004), a lower size of thrombi (p<0.001) and lower circulating anti-β2GPI Abs in comparison to mice fed with domain-V or PBS (p<0.002). Likewise, Domain-I
fed mice had a lowered inflammatory response, exhibited by decreased expression of inflammatory cytokines (IFNγ, IL-6, IL-17) and elevated production of IL-10 anti-inflammatory cytokine by splenocytes. Moreover, the anti-inflammatory response in the domain-I fed APS mice was associated with alterations in circulating miRNAs, which is associated with immunomodulation of the immune network.
Conclusions
Our results show that DI-β2GPI fed APS mice developed tolerance scenario manifested by a reduction in fetal loss, thrombi size, inhibition of inflammatory cytokine production and upregulation of IL-10 and T regulatory cells. This sequence of events is associated with circulating plasma miRNA related to the immune network. Therefore we propose the DI-β2GPI derivative treatment for patients with APS.