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42. Kongress der Deutschen Gesellschaft für Rheumatologie, 28. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie, 24. Wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie

17.-20. September 2014, Düsseldorf

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Bortezomib ameliorates the disease progression due to ovalbumin immunization in NZB/W F1 Lupus prone mice

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  • Laleh Khodadadi - Deutsches Rheuma-Forschungszentrum (DRFZ), Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
  • Qingyu Cheng - Deutsches Rheuma-Forschungszentrum (DRFZ), Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
  • Oliver Winter - Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
  • Adriano Taddeo - Deutsches Rheuma-Forschungszentrum (DRFZ), Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
  • Andreas Radbruch - Deutsches Rheuma-Forschungszentrum (DRFZ), Berlin
  • Bimba Franziska Hoyer - Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Deutsches Rheuma-Forschungszentrum (DRFZ), Berlin
  • Falk Hiepe - Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie der Charité - Universitätsmedizin Berlin und Deutsches RheumaForschungszentrum Berlin - ein Institut der Leibniz-Gemeinschaft, Berlin

Deutsche Gesellschaft für Rheumatologie. Deutsche Gesellschaft für Orthopädische Rheumatologie. Gesellschaft für Kinder- und Jugendrheumatologie. 42. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 28. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 24. wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR). Düsseldorf, 17.-20.09.2014. Düsseldorf: German Medical Science GMS Publishing House; 2014. DocER.09

doi: 10.3205/14dgrh076, urn:nbn:de:0183-14dgrh0769

Published: September 12, 2014

© 2014 Khodadadi et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Background: Plasma cell depletion with bortezomib (Bz) can prevent the development of lupus nephritis and prolong survival in NZB/W mice. Here, we studied the effect of the immunization with OVA in combination with bortezomib on the disease in NZB/W mice.

Methods: NZB/W F1 female mice 16 week-old (early disease stage) were divided into 3 groups as follows: 1. Non-immunized mice as a control group, 2. Immunized mice; mice immunized with alum-precipitated OVA i.p and boosted 3 weeks after primary immunization, 3. Immunized mice as group 2 receiving two shots of bortezomib (0.75 mg/kg, i.v) at 48 and 12 hour before secondary immunization. The numbers of autoreactive anti-dsDNA antibody secreting cells (ASCs) were assessed one month after secondary immunization by ELISPOT. Parameters including anti-OVA antibody level, anti-dsDNA antibody level, proteinuria and survival rate were also analyzed.

Results: Total number of IgM anti-dsDNA ASCs in the immunized group had tendency to increase in the bone marrow and spleen compared to non-immunized, while in the group receiving Bz, they were remained comparable with non-immunized mice. Immunized NZB/W mice (group 2) developed proteinuria, which was earlier and stronger than in the non-immunized mice (group 1) and in mice additionally treated with Bz before booster immunization (group 3). Survival rate of immunized mice was reduced in comparison to the group 3 treated with Bz, while group 1 showed the longest survival. Autoantibody levels in groups 2 and 3 were higher than in group 1. This could be confirmed by analysis of anti-dsDNA antibody secreting cells in spleen and bone marrow. The Bz treatment before the secondary OVA immunization resulted in lower anti-OVA antibody levels than in immunized mice without Bz treatment.

Conclusion: Immunization with alum-precipitated OVA accelerates autoimmunity in NZB/W mice. This effect can be ameliorated by plasma cell depletion with bortezomib.