title: Adjuvant immunization induces high levels of pathogenic antiphospholipid antibodies in genetically prone mice: another facet of the ASIA syndrome.
abstract: Adjuvants may induce autoimmune diseases in susceptible individuals, a phenomenon recently defined as autoimmune/inflammatory syndrome induced by adjuvants (ASIA). Patients with both antiphospholipid antibodies (aPL) and the genetic coagulopathy factor V Leiden (FVL) are frequently found. We therefore evaluated whether adjuvant can induce aPL in heterozygous FVL mice. aPL were measured in naïve mice and at 1 and 5 months after immunization with either complete or incomplete Freund's adjuvant (CFA, IFA) in FVL and control C57/B6 background mice. We defined antibody levels 3 SD above the mean of C57/B6 mice immunized with adjuvant as positive (specificity of 99%). For β(2)GPI-dependent aPL, 28.6% (6/21) of FVL mice 5 months after immunization with adjuvant (both IFA and CFA) were positive compared with 4.8% (1/22) of FVL mice 1 month after adjuvant and 0% of naïve FVL and C57/B6 mice (0/16, p < 0.001). aPL levels correlated with behavioral hyperactivity in the staircase test. FVL mice immunized with adjuvant did not develop β(2)GPI-independent aPL. We hypothesize that the FVL aPL association is not a coincidence, but that chronic coagulation defects combined with external inflammatory stimuli analogous to adjuvant may induce aPL and also antiphospholipid syndrome, thus supporting the notion of ASIA.
authors.affiliation: Department of Neurology and Sagol Center for Neurosciences, Sheba Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. avivakatzav@gmail.com
authors.forename: A
authors.initials: A
authors.lastname: Katzav
authors.forename: S
authors.initials: S
authors.lastname: Kivity
authors.forename: M
authors.initials: M
authors.lastname: Blank
authors.forename: Y
authors.initials: Y
authors.lastname: Shoenfeld
authors.forename: J
authors.initials: J
authors.lastname: Chapman
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects*; D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000097:blood / Q000276:immunology*; D001327:Autoimmune Diseases / Q000097:blood / Q000139:chemically induced* / Q000235:genetics* / Q000276:immunology*; D005165:Factor V / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
chemical_list: D000276:Adjuvants, Immunologic; D017152:Antibodies, Antiphospholipid; C095381:factor V Leiden; D005165:Factor V