A major autoepitope is present on the amino terminus of a human SS-A/Ro polypeptide.
A human SS-A/Ro antigen is present on the polypeptide component of a particle composed of hyRNA and a 60 kD protein. We have now purified the Wil-2 cell 60 kilo dalton (kD) SS-A/Ro protein and determined its amino-terminal amino acid sequence. A synthetic peptide corresponding to residues 7 to 24 of this sequence (RoSP7-24) exhibited enzyme-linked immunosorbent assay (ELISA) binding activity with immunodiffusion-defined, monospecific anti-SS-A/Ro sera. In addition, ELISA binding of monospecific anti-SS-A/Ro sera to native SS-A/Ro antigen was partially inhibited (35%) by KLH-RoSP7-24. Sera from patients known to frequently produce precipitating anti-SS-A/Ro antibody (subacute cutaneous lupus erythematosus [SCLE], 56 patients; Sjögren's syndrome [SS], 41 patients; mothers of infants with neonatal LE [NLE], 10 individuals; infants with congenital heart block [CHB], 5 patients) were tested for reactivity to RoSP7-24 in ELISA. Overall, 38% of SCLE sera, 36% of SS sera, 50% of maternal NLE sera and 20% of CHB infant sera had anti-RoSP7-24 binding levels greater than 2 standard deviations above the mean of that of normal individuals. Of the sera which had anti-SS-A/Ro detected by double immunodiffusion and/or counterimmunoelectrophoresis, 68% of SCLE patients, 71% of SS patients, 55% of NLE mothers and 20% of CHB infants had significantly elevated RoSP7-24 ELISA binding levels. These findings strongly suggest that a major autoepitope of native human SS-A/Ro resides on the amino terminal portion of the Wil-2 SS-A/Ro 60 kD polypeptide.(ABSTRACT TRUNCATED AT 250 WORDS)
Lieu
T S
TS
Department of Dermatology, University of Texas Health Science Center, Dallas 75235.
Newkirk
M M
MM
Arnett
F C
FC
Lee
L A
LA
Deng
J S
JS
Capra
J D
JD
Sontheimer
R D
RD
D000974:Antibodies, Antinuclear / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology; D001665:Binding Sites; D000939:Epitopes / Q000276:immunology; D006327:Heart Block / Q000151:congenital / Q000276:immunology; D006801:Humans; D008178:Lupus Erythematosus, Cutaneous / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000151:congenital / Q000276:immunology; D008297:Male; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins; D012859:Sjogren's Syndrome / Q000276:immunology; D000099207:SS-A Antigen
D000974:Antibodies, Antinuclear; D001324:Autoantigens; D000939:Epitopes; D010446:Peptide Fragments; D010455:Peptides; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins; D000099207:SS-A Antigen; C116006:RO60 protein, human; C035356:SS-A antibodies