Responses in vitro of peripheral blood lymphocytes from patients with myasthenia gravis to stimulation with human acetylcholine receptor α-chain peptides: Analysis in relation to age, thymic abnormality, and ethnicity

Peripheral blood lymphocytes (PBLs) were isolated from 24 patients with myasthenia gravis of three ethnic groups (Caucasian, African American, and Hispanic) and ten healthy individuals. We determined the in vitro proliferative responses of the PBL samples to each of 18 overlapping synthetic peptides corresponding to the entire main extracellular domain (residues 1-210) of the α-subunit of human acetylcholine receptor. The profiles of the T-cell responses (expressed in stimulation index [SI]) to the peptides varied among the 24 patient samples. There was a significant difference in the overall patient responses relative to controls toward 17 of 18 peptides. T cells from the patients gave responses greater than control mean SI + 4 standard deviation (ZSI > 4) to 2∼9 peptides/sample. Six peptides, α23-38, α34-49, α78-93, α122-138, α146-162, and α182-198, were recognized with Z > 4 level by 42% to 58% of the patients' PBLs. The grouped patient responses, divided according to age, thymic diagnosis, or ethnicity, were compared with controls and with each other. Significant differences were observed between early- and late-onset cases in recognition of residues α34-49 (p = 0.015) and α78-93 (p = 0.053), and in recognition of residues α12-27, α56-71, α134-150, and α146-162 (0.0072 < p < 0.064) when two ethnic groups were compared with each other.