BACKGROUND AND AIMS: Anti-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. METHODS: We looked for the induction of HMGB1-specific B and T cell responses by a western-type diet (WTD) in the Apoe(-/-) mouse model of atherosclerosis. We also determined whether modifying the responses modulates atherosclerosis. RESULTS: In the plasma of male Apoe(-/-) mice fed WTD, the level of anti-HMGB1 antibodies (Abs) was detected at ∼50 μg/ml, which was ∼6 times higher than that in either Apoe(-/-) mice fed a normal chow or Apoe(+/+) mice fed WTD (p ≤ 0.0005). The Abs were directed largely toward a novel, dominant epitope of HMGB1 named HMW4; accordingly, compared with chow-fed mice, WTD-fed Apoe(-/-) mice had more activated HMW4-reactive B and T cells (p = 0.005 and p = 0.01, respectively). Compared with mock-immunized mice, Apoe(-/-) 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 ∼30% increase in aortic arch lesions (p ≤ 0.01) by two methods. In contrast, Apoe(-/-) 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 ∼40% decrease in aortic arch lesions (p ≤ 0.03). CONCLUSIONS: Anti-HMGB1 autoimmunity may potentially play a role in atherogenesis.
BACKGROUND AND AIMS: Anti-HMGB1autoimmunity plays a role in systemic lupus erythematosus (SLE). Because SLE increases atherosclerosis, we asked whether the same autoimmunity might play a role in atherogenesis. METHODS: We looked for the induction of HMGB1-specific B and T cell responses by a western-type diet (WTD) in the Apoe(-/-) mouse model of atherosclerosis. We also determined whether modifying the responses modulates atherosclerosis. RESULTS: In the plasma of male Apoe(-/-) mice fed WTD, the level of anti-HMGB1 antibodies (Abs) was detected at ∼50 μg/ml, which was ∼6 times higher than that in either Apoe(-/-) mice fed a normal chow or Apoe(+/+) mice fed WTD (p ≤ 0.0005). The Abs were directed largely toward a novel, dominant epitope of HMGB1 named HMW4; accordingly, compared with chow-fed mice, WTD-fed Apoe(-/-) mice had more activated HMW4-reactive B and T cells (p = 0.005 and p = 0.01, respectively). Compared with mock-immunized mice, Apoe(-/-) mice immunized with HMW4 along with an immunogenic adjuvant showed proportional increases in anti-HMW4IgG and IgM Abs, HMW4-reactive B-1 and B-2 cells, and HMW4-reactive Treg and Teff cells, which was associated with ∼30% increase in aortic arch lesions (p ≤ 0.01) by two methods. In contrast, Apoe(-/-) mice immunized with HMW4 using a tolerogenic adjuvant showed preferential increases in anti-HMW4IgM (over IgG) Abs, HMW4-reactive B-1 (over B-2) cells, and HMW4-specific Treg (over Teff) cells, which was associated with ∼40% decrease in aortic arch lesions (p ≤ 0.03). CONCLUSIONS: Anti-HMGB1autoimmunity may potentially play a role in atherogenesis.
Authors: Melanie L Dart; Ewa Jankowska-Gan; Guorui Huang; Drew A Roenneburg; Melissa R Keller; Jose R Torrealba; Aaron Rhoads; Byoungjae Kim; Joseph L Bobadilla; Lynn D Haynes; David S Wilkes; William J Burlingham; Daniel S Greenspan Journal: Circ Res Date: 2010-09-02 Impact factor: 17.367
Authors: T L Stevens; A Bossie; V M Sanders; R Fernandez-Botran; R L Coffman; T R Mosmann; E S Vitetta Journal: Nature Date: 1988-07-21 Impact factor: 49.962
Authors: U Andersson; H Wang; K Palmblad; A C Aveberger; O Bloom; H Erlandsson-Harris; A Janson; R Kokkola; M Zhang; H Yang; K J Tracey Journal: J Exp Med Date: 2000-08-21 Impact factor: 14.307
Authors: Christine G Parks; Aline de Souza Espindola Santos; Medha Barbhaiya; Karen H Costenbader Journal: Best Pract Res Clin Rheumatol Date: 2017-10-21 Impact factor: 4.098