Antibody dependent cell-mediated cytotoxicity--an additional mechanism in human autoimmune myasthenia gravis.
Myasthenia gravis (MG) is an autoimmune disease characterised by serum anti-acetylcholine receptor (AChR) antibodies and several pathogenic mechanisms for the action of these antibodies have been elucidated. In this study, we have analysed a possible additional mechanism for these antibodies, namely antibody-dependent cell-mediated cytotoxicity (ADCC). Using as target cells a cell line expressing AChR, we could show an increased ADCC mediated by sera from MG patients. Sera with AChR antibodies induced a higher cytotoxicity than sera from patients without these antibodies or healthy individuals. Sera from MG patients with thymoma induced a higher cytotoxic effect than sera from other patients. There was a strong positive correlation between the concentration of AChR antibodies and cytotoxicity mediated by purified IgG fractions from thymoma patients. In addition, there was a higher cytotoxicity mediated by sera from thymoma patients with extended dinucleotide repeats, (AT)n repeats, in the CTLA-4 gene. ADCC mediated by AChR antibodies may thus be another possible pathogenic mechanism that could operate in MG patients, especially in patients with thymoma.
Xu
B Y
BY
Immunological Research Unit, Center of Molecular Medicine, Department of Medicine, Karolinska Hospital, Stockholm, Sweden. biying.xu@cmm.ki.se
Pirskanen
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R
Lefvert
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AK
D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology* / Q000302:isolation & purification; D002860:Chromium Radioisotopes; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000302:isolation & purification; D009157:Myasthenia Gravis / Q000453:epidemiology / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000276:immunology*; D016036:Seroepidemiologic Studies; D013945:Thymoma / Q000453:epidemiology / Q000276:immunology
D001323:Autoantibodies; D002860:Chromium Radioisotopes; D007074:Immunoglobulin G; D011950:Receptors, Cholinergic