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Lupus. 2012 Feb;21(2):210-6. doi: 10.1177/0961203311429550.

Adjuvant immunization induces high levels of pathogenic antiphospholipid antibodies in genetically prone mice: another facet of the ASIA syndrome.

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Department of Neurology and Sagol Center for Neurosciences, Sheba Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.


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.

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