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Combined short‐term immunotherapy for experimental autoimmune myasthenia gravis
Author(s) -
Pestronk Alan,
Drachman Daniel B.,
Teoh Robert,
Adams Robert N.
Publication year - 1983
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410140210
Subject(s) - myasthenia gravis , cyclophosphamide , medicine , immunology , immunotherapy , immune system , bone marrow , acetylcholine receptor , antibody , antigen , chemotherapy , receptor
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 animals' 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.