Myasthenia Gravis Patients have a Cellular Immune Response against Titin
Myasthenia gravis (MG) is caused by antibodies against the acetylcholine receptor (AChR). However, some MG patients have antibodies against non-AChR epitopes of skeletal muscle including titin. In this study, we tested peripheral blood lymphocytes from 11 MG patients and 13 blood donors in a lymphocyte transformation test using the antigen MGT-30, a titin epitope that represents the main immunogenic region. Stimulation index (SI) was defined as counts per minute (cpm) in stimulated culture minus background divided by cpm in unstimulated culture minus background. MGT-30 caused a significant stimulation of T-cells from titin-antibody positive MG patients; SI=1.84±0.77, compared with titin-antibody negative patients; SI=0.67±0.28 (p=0.01), and blood-donors; SI=0.65±0.21 (p=0.0005). SI after PHA stimulation was similar in MG patients with and without titin-antibodies and blood-donors. After MGT-30 stimulation, IL-4 concentrations in the supernatant were 84–150pg/mL in all 4 titin-positive patients examined. IL-4 levels were below the detection limit for the ELISA used (60pm/ml) in the cultures from the 8 blood-donors and the 1 titin-negative MG patient that were tested. Thus, MG patients with anti-titin antibodies also have a T-cell mediated immune reactivity against titin.
KeywordsStimulation Index Thymic Hyperplasia Lymphocyte Transformation Test Unstimulated Culture Nicotinic Receptor Alpha
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