Immunization with hepatitis B vaccine accelerates SLE-like disease in a murine model

被引:60
作者
Agmon-Levin, Nancy [1 ,2 ]
Arango, Maria-Teresa [1 ,3 ,4 ]
Kivity, Shaye [1 ,2 ,5 ]
Katzav, Aviva [6 ,7 ]
Gilburd, Boris [1 ]
Blank, Miri [1 ]
Tomer, Nir [1 ]
Volkov, Alex [8 ]
Barshack, Iris [8 ]
Chapman, Joab [6 ,7 ]
Shoenfeld, Yehuda [1 ,9 ]
机构
[1] Sheba Med Ctr, Zabludowicz Ctr Autoimmune Dis, IL-52621 Tel Hashomer, Israel
[2] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel
[3] Univ Rosario, Doctoral Program Biomed Sci, Bogota 111221, Colombia
[4] Univ Rosario, Ctr Autoimmune Dis Res CREA, Bogota 111221, Colombia
[5] Sheba Med Ctr, Dr Pinchas Borenstein Talpiot Med Leadership Prog, IL-52621 Tel Hashomer, Israel
[6] Sheba Med Ctr, Dept Neurol, IL-52621 Tel Hashomer, Israel
[7] Sheba Med Ctr, Sagol Neurosci Ctr, IL-52621 Tel Hashomer, Israel
[8] Sheba Med Ctr, Inst Pathol, IL-52621 Tel Hashomer, Israel
[9] Tel Aviv Univ, Incumbent Laura SchwarzKip Chair Autoimmun, IL-69978 Tel Aviv, Israel
关键词
Hepatitis B vaccine; SLE; Vaccination; Autoimmunity; Autoimmune/autoinflammatory syndrome induced by adjuvant (ASIA); Neuro-cognitive tests; SYSTEMIC-LUPUS-ERYTHEMATOSUS; HUMAN-PAPILLOMAVIRUS VACCINE; CONNECTIVE-TISSUE DISEASE; GUILLAIN-BARRE-SYNDROME; ADJUVANTS ASIA; MICE; ALUMINUM; ANTIBODIES; BRAIN; INFLUENZA;
D O I
10.1016/j.jaut.2014.06.006
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Hepatitis-B vaccine (HBVv) can prevent HBV-infection and associated liver diseases. However, concerns regarding its safety, particularly among patients with autoimmune diseases (i.e. SLE) were raised. Moreover, the aluminum adjuvant in HBVv was related to immune mediated adverse events. Therefore, we examined the effects of immunization with HBVv or alum on SLE-like disease in a murine model. NZBWF1 mice were immunized with HBVv (Engerix), or aluminum hydroxide (alum) or phosphate buffered saline (PBS) at 8 and 12 weeks of age. Mice were followed for weight, autoantibodies titers, blood counts, proteinuria, kidney histology, neurocognitive functions (novel object recognition, staircase, Y-maze and the forced swimming tests) and brain histology. Immunization with HBVv induced acceleration of kidney disease manifested by high anti-dsDNA antibodies (p < 0.01), early onset of proteinuria (p < 0.05), histological damage and deposition of HBs antigen in the kidney. Mice immunized with HBVv and/or alum had decreased cells counts mainly of the red cell lineage (p < 0.001), memory deficits (p < 0.01), and increased activated microglia in different areas of the brain compare with mice immunized with PBS. Anxiety-like behavior was more pronounced among mice immunized with alum. In conclusion, herein we report that immunization with the HBVv aggravated kidney disease in an animal model of SLE. Immunization with either HBVv or alum affected blood counts, neurocognitive functions and brain gliosis. Our data support the concept that different component of vaccines may be linked with immune and autoimmune mediated adverse events. (C) 2014 Elsevier Ltd. All rights reserved.
引用
收藏
页码:21 / 32
页数:12
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