Responses in vitro of peripheral blood lymphocytes from patients with myasthenia gravis to stimulation with human acetylcholine receptor alpha-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 alpha-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 (Z(SI) > 4) to 2 approximately 9 peptides/sample. Six peptides, alpha 23-38, alpha 34-49, alpha 78-93, alpha 122-138, alpha 146-162, and alpha 182-198, 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 alpha 34-49 (p = 0.015) and alpha 78-93 (p = 0.053), and in recognition of residues alpha 12-27, alpha 56-71, alpha 134-150, and alpha 146-162 (0.0072 < p < 0.064) when two ethnic groups were compared with each other.
Oshima
Minako
M
Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Deitiker
Philip R
PR
Mosier
Dennis R
DR
Smith
R Glenn
RG
Atassi
M Zouhair
MZ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D015551:Autoimmunity / Q000187:drug effects / Q000276:immunology*; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009157:Myasthenia Gravis / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D021122:Protein Subunits / Q000276:immunology; D044469:Racial Groups; D011950:Receptors, Cholinergic / Q000737:chemistry / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D010446:Peptide Fragments; D021122:Protein Subunits; D011950:Receptors, Cholinergic