TITIN ANTIBODY-POSITIVE MYASTHENIA-GRAVIS PATIENTS HAVE A CELLULAR IMMUNE-RESPONSE AGAINST THE MAIN IMMUNOGENIC REGION OF TITIN

Some myasthenia gravis (MG) patients have antibodies against non-acety lcholine receptor (AChR) epitopes of skeletal muscle including titin. Peripheral blood lymphocytes from 11 MG patients and 13 blood-donors w ere tested for lymphocyte proliferation after stimulation with the tit in peptide MGT-30, which represents the main immunogenic region. Four out of seven titin antibody positive patients had significant stimulat ion defined as a stimulation index (SI) above 2. Neither of the four t itin antibody negative patients nor the 13 blood-donors had SI above 2 (p = 0.001). Mean SI was significantly higher for T-cells from titin antibody positive MG patients, SI = 2.2 +/- 0.8, compared to titin ant ibody negative patients, SI = 0.9 +/- 0.2 (p = 0.01), and blood-donors , SI = 0.8 +/- 0.3 (p < 0.0005). After MGT-30 stimulation, IL-4 was de tected in the blood lymphocyte culture supernatant from four of the fi ve MG patients examined, but from none of the eight blood-donors. Thus , MG patients with anti-titin antibodies have a T-cell mediated immune reaction against titin.