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A8.26 Bortezomib ameliorates the disease progression due to ovalbumin immunisation in NZB/W F1 lupus prone mice
  1. L Khodadadi1,
  2. Q Cheng1,
  3. O Winter2,
  4. A Taddeo1,
  5. A Radbruch1,
  6. BF Hoyer1,2,
  7. F Hiepe1,2
  1. 1 German Rheumatism Research Center Berlin (DRFZ) – A Leibniz Institute, Germany
  2. 2 Department of Rheumatology and Clinical Immunology, Charité University Hospital Berlin, Germany

Abstract

Background and objectives Plasma cell depletion with bortezomib can prevent the development of lupus nephritis and prolong survival in NZB/W mice. Here, we studied the effect of the immunisation 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-immunised mice as a control group, 2. Immunised mice; mice immunised with alum-precipitated OVA i.p and boosted 3 weeks after primary immunisation, 3. Immunised mice as group 2 receiving two shots of bortezomib (0.75 mg/kg, i.v) at 48 and 12 h before secondary immunisation. The numbers of anti-dsDNA antibody secreting cells (ASCs) were assessed in spleen and bone marrow by ELISPOT one month after secondary immunisation. Moreover we investigated serologic parameters including anti-OVA and anti-dsDNA antibody levels by ELISA as well as proteinuria and survival rate.

Results Immunised mice (group 2) developed proteinuria, which occurred earlier and stronger than in the non-immunised mice and in mice additionally treated with Bz before booster immunisation (group 3). Survival rate of immunised mice was reduced in comparison to group 3 treated with Bz while group 1 showed the longest survival. Autoantibody levels in group 2 and 3 were higher than in the control group 1. Mice immunised with OVA showed a tendency to higher numbers of IgM anti-dsDNA ASCs in the bone marrow and spleen than in non-immunised mice while IgG anti-dsDNA ASCs counts analysed in mice immunised with OVA and treated with Bz, were comparable with their counts in non-immunised mice. The Bz treatment before the secondary OVA immunisation resulted in lower anti-OVA antibody levels than in immunised mice without Bz treatment.

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

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