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Open Access

Allogeneic bone marrow transplantation can suppress established and otherwise chronic collagen-induced arthritis after a nonmyeloablative conditioning regimen employing anti-CD40 ligand monoclonal antibody

  • R Flierman1,
  • L Morgan2,
  • L van Duivenvoorde1,
  • RRP de Vries2,
  • WE Fibbe3,
  • TJW Huizinga1,
  • REM Toes1 and
  • JM van Laar1
Arthritis Res Ther20046(Suppl 1):95

https://doi.org/10.1186/ar1137

Received: 16 January 2004

Published: 25 February 2004

Keywords

Rheumatoid ArthritisBone Marrow TransplantationTotal Body IrradiationAllogeneic Bone Marrow TransplantationAutologous Bone Marrow Transplantation

Objective

Allogeneic bone marrow transplantation (BMT) may be more effective than autologous BMT as a treatment for patients with severe autoimmune diseases, such as rheumatoid arthritis (RA). However, the application of allogeneic BMT for treatment of RA is not yet feasible because of the high-dose immunosuppression that is used before and after BMT. Therefore, in this study collagen-induced arthritis (CIA) – the classic mouse model for RA – was used to compare the effects of allogeneic and syngeneic BMT after less toxic, nonlethal (i.e. nonmyeloablative) conditioning regimens on established disease in DBA/1 (H-2q) mice.

Methods

We induced arthritis in normal DBA/1 (H-2q) mice by immunization with type II collagen (CII) in complete Freund's adjuvans (CFA). To allow engraftment, we made use of anti-CD40 ligand monoclonal antibody (one injection of 0.5 mg ip) and nonlethal total body irradiation (TBI) of 6.0 Gy before BMT with 1.0 × 10e7 total BM cells from syngeneic DBA/1 (H-2q) mice or from fully MHC-mismatched allogeneic BALB/c (H-2d) mice. After treatment, mice were scored for clinical arthritis, and serum was taken to measure the amounts of CII-specific antibodies.

Results

We were able to induce stable and long-term (> 300 days) donor chimerism (> 95%) after transplantation with fully MHC-mismatched total BM cells from allogeneic BALB/c (H-2d) mice using a nonmyeloablative conditioning regimen. After initial exarcebation of arthritis shortly after allogeneic BMT, due to a graft-versus-host (GvH)/host-versus-graft (HvG) response, mice receiving allogeneic BM cells showed a significant suppression of arthritis and CII-specific antibodies. Syngeneic BMT was also effective in suppressing clinical disease, although no effects on CII-specific antibodies could be observed.

Conclusion

These data indicate that nonmyeloablative conditioning using low-dose TBI and anti-CD40 ligand monoclonal antibody followed by MHC mismatched allogeneic BMT results in donor chimerism, disappearence of pathogeneic autoantibodies and improvement in disease activity.
Figure 1
Figure 1

Allogeneic BMT can suppress both clinical disease and pathogeneic antibodies. (a) Clinical disease over time. (b) Anti-type II collagen antibodies are decreased after treatment.

Authors’ Affiliations

(1)
Department of Rheumatology, LUMC, Leiden, The Netherlands
(2)
Department of Immunohematology and Bloodbank, LUMC, Leiden, The Netherlands
(3)
Department of Hematology, Leiden, The Netherlands

Copyright

© The Author(s) 2004

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