Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5942585 | Atherosclerosis | 2016 | 8 Pages |
â¢The western type diet that accelerates atherogenesis also induces anti-HMGB1 autoimmunity in Apoeâ/â mice.â¢Most of the induced anti-HMGB1 Ab binds to a novel dominant epitope called HMW4.â¢Immunization with HMW4 can modify the disease outcome.
Background and aimsAnti-HMGB1 autoimmunity plays a role in systemic lupus erythematosus (SLE). Because SLE increases atherosclerosis, we asked whether the same autoimmunity might play a role in atherogenesis.MethodsWe looked for the induction of HMGB1-specific B and T cell responses by a western-type diet (WTD) in the Apoeâ/â mouse model of atherosclerosis. We also determined whether modifying the responses modulates atherosclerosis.ResultsIn the plasma of male Apoeâ/â mice fed WTD, the level of anti-HMGB1 antibodies (Abs) was detected at â¼50 μg/ml, which was â¼6 times higher than that in either Apoeâ/â mice fed a normal chow or Apoe+/+ mice fed WTD (p â¤Â 0.0005). The Abs were directed largely toward a novel, dominant epitope of HMGB1 named HMW4; accordingly, compared with chow-fed mice, WTD-fed Apoeâ/â mice had more activated HMW4-reactive B and T cells (p = 0.005 and p = 0.01, respectively). Compared with mock-immunized mice, Apoeâ/â mice immunized with HMW4 along with an immunogenic adjuvant showed proportional increases in anti-HMW4 IgG and IgM Abs, HMW4-reactive B-1 and B-2 cells, and HMW4-reactive Treg and Teff cells, which was associated with â¼30% increase in aortic arch lesions (p â¤Â 0.01) by two methods. In contrast, Apoeâ/â mice immunized with HMW4 using a tolerogenic adjuvant showed preferential increases in anti-HMW4 IgM (over IgG) Abs, HMW4-reactive B-1 (over B-2) cells, and HMW4-specific Treg (over Teff) cells, which was associated with â¼40% decrease in aortic arch lesions (p â¤Â 0.03).ConclusionsAnti-HMGB1 autoimmunity may potentially play a role in atherogenesis.