Combined short-term immunotherapy for experimental autoimmune myasthenia gravis

Journal Article · Mon Aug 01 04:00:00 EDT 1983 · Ann. Neurol.; (United States)

DOI:https://doi.org/10.1002/ana.410140210· OSTI ID:6914862

Pestronk, A; Drachman, D B; Teoh, R; Adams, R N

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), Journal Name: Ann. Neurol.; (United States) Vol. 14:2; ISSN ANNED
• Country of Publication: United States
• Language: English

Related Subjects

550600 -- Medicine
560152* -- Radiation Effects on Animals-- Animals
62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACETYLCHOLINE
ALKYLATING AGENTS
AMINES
AMMONIUM COMPOUNDS
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
ANTIGEN-ANTIBODY REACTIONS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BIOLOGICAL RADIATION EFFECTS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
BONE MARROW
CONNECTIVE TISSUE CELLS
DISEASES
DRUGS
ENDOXAN
ESTERS
HEMATOPOIETIC SYSTEM
IMMUNE REACTIONS
IMMUNOSUPPRESSIVE DRUGS
IMMUNOTHERAPY
LEUKOCYTES
LYMPHOCYTES
MAMMALS
MATERIALS
MEDICINE
NERVOUS SYSTEM DISEASES
NEUROREGULATORS
NUCLEAR MEDICINE
ORGANIC COMPOUNDS
ORGANS
PARASYMPATHOMIMETICS
QUATERNARY COMPOUNDS
RADIATION EFFECTS
RADIOLOGY
RADIOSENSITIVITY
RADIOTHERAPY
RATS
RODENTS
SOMATIC CELLS
THERAPY
TISSUES
TRANSPLANTS
VERTEBRATES