Combined short-term immunotherapy for experimental autoimmune myasthenia gravis
A therapeutic strategy was designed to eliminate the humoral immune response to acetylcholine receptor (AChR) in ongoing experimental autoimmune myasthenia gravis (EAMG). Rats with EAMG were treated with a protocol consisting of three components: (1) A single high dose of cyclophosphamide (200 mg/kg) was used to produce a rapid and sustained fall in the anti-AChR antibody levels by preferential destruction of antibody-producing B-lymphocytes. ''Memory'' lymphocytes were not eliminated by cyclophosphamide. (2) Irradiation (600 rads) was used to eliminate the ''memory'' cells. It eliminated the anamnestic response to a challenge with the antigen AChR. (3) Bone marrow transplantation was used to repopulate the hematopoietic system after the otherwise lethal dose of cyclophosphamide. We used bone marrow from syngeneic rats with active EAMG to simulate an autologous transplant. Rats with EAMG treated with this combined protocol showed a prompt and sustained fall in the anti-AChR antibody levels and had no anamnestic response to a challenge with AChR. Thus, an affected animal's own marrow could be stored and used later for repopulation after cyclophosphamide-irradiation treatment. This treatment eliminates the animal's ongoing immune responses and reconstitutes the immune system in its original state. The success of this approach suggests that, if their safety could be established, similar ''curative'' strategies might be developed for the treatment of patients with severe antibody-mediated autoimmune disorders, such as myasthenia gravis.
- OSTI ID:
- 6914862
- Journal Information:
- Ann. Neurol.; (United States), Vol. 14:2
- Country of Publication:
- United States
- Language:
- English
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62 RADIOLOGY AND NUCLEAR MEDICINE
BONE MARROW
TRANSPLANTS
IMMUNE REACTIONS
BIOLOGICAL RADIATION EFFECTS
LYMPHOCYTES
RADIOSENSITIVITY
NERVOUS SYSTEM DISEASES
IMMUNOTHERAPY
RADIOTHERAPY
ACETYLCHOLINE
ANTIGEN-ANTIBODY REACTIONS
ENDOXAN
RATS
ALKYLATING AGENTS
AMINES
AMMONIUM COMPOUNDS
ANIMAL CELLS
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ESTERS
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LEUKOCYTES
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560152* - Radiation Effects on Animals- Animals
550600 - Medicine