Pediatric Rheumatology Online Journal → July 2003 → Childhood Lupus→ Immunology and Immunogenetics → Abstract #90
                                                                August 2003 → Newer Treatments → Bone Marrow/Stem Cell Transplantation → Abstract #90

TREATMENT OF BXSB LUPUS MICE WITH FULLY MATCHED ALLOGENEIC BONE MARROW TRANSPLANTATION USING NONMYELOABLATIVE CONDITIONING

O. Y. Jones,¹ A. M. Steele,¹ Y. Marikar,¹ Y. Chang,¹ J. M. Jones,¹ R. A. Cahill,¹ R. A. Good.¹

¹Pediatrics, University of South Florida/ All Children's Hospital, St. Petersburg, FL

Background: Male BXSB mice (H-2^b) spontaneously develop Systemic Lupus Erythematosus (SLE)-like autoimmune disease with immune complex mediated renal pathology that is evident at 10 weeks of age and inducing death by 50% at 40 weeks of age.
Methods: Male BXSB at 20 weeks of age were conditioned with sublethal total body radiation (550cGy) four hours prior to tail-vein infusion of non-fractionated bone marrow cells (20x10⁶/mouse) from male Green florescent transgenic (GFP) C57BL/6 mice (GFP-Tg, H-2^b). The control groups were untreated age-matched BSXB mice and BXSB treated mice with radiation only. Mice were sacrificed at 10 and 20 weeks post bone marrow transplantation (BMT) for renal histopathology scoring. The donor chimerism was determined by flow cytometry of blood.
Results: The transplanted mice achieved 30-50% donor chimerism (% GFP positive cells) and remained clinically free of edema and lymphadenopathy. There was a significant improvement of the renal pathology in the transplanted mice at both 10 weeks and 20 weeks (n=6, mean score 0.8) post transplantation compared to non-treated age-matched controls (n=3, mean score = 3.8 at 20 weeks). The radiation treatment also caused some transient improvement that was evident at 10 weeks post radiation, but not at 20 weeks post transplantation (n=4, mean score 1.98). BMT also reduced the characteristic lymph node monocytosis (% CD11b⁺Gr1^- cells) of these BXSB mice at 20 weeks from 18.3 ±4.5 to 7.3 ± 2.4 (not detected in radiation controls).
Conclusion: Based on these results, treatment of SLE by BMT may not require complete myeloablation. The healthy hematopoietic stem cells introduced were able to dominate the hosts immune network and decrease autoimmune reactions. Further studies of the mechanisms involved are being further investigated.