Implications of anti-ro/Sjögren's syndrome A antigen autoantibody in normal sera for autoimmunity

• Published in: The Journal of clinical investigation Vol. 79; no. 3; pp. 841 - 846
• Main Authors: GAITHER, K. K, FOX, O. F, YAMAGATA, H, MAMULA, M. J, REICHLIN, M, HARLEY, J. B
• Format: Journal Article
• Language: English
• Published: Ann Arbor, MI American Society for Clinical Investigation 01.03.1987
• Subjects: Adult; Autoantibodies - analysis; Autoantibodies - immunology; Autoantigens - immunology; Biological and medical sciences; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique; Humans; Immunoglobulin Fab Fragments - immunology; Immunoglobulin G - immunology; Immunosorbent Techniques; Male; Medical sciences; Middle Aged; Ribonucleoproteins; RNA, Small Cytoplasmic; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; SS-B Antigen; Human; Immunopathology; Connective tissue disease; Eye disease; Skin disease; Ro antigen; Autoantibody; ENT disease; Sjogren syndrome
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI112892

We have applied a sensitive assay to analyze lupus and Sjögren's syndrome autoantibodies in 40 normal sera. Seven of these bound Ro/Sjögren's syndrome A antigen (SSA). Although this binding was 1,000-fold lower than the highest anti-Ro/SSA level measured from patients, it was inhibited by human Ro/SSA. Positive normal serum-bound Ro/SSA in Western immunoblots and binding activity was demonstrated in the F(ab')2 fragment of IgG. Affinity purification of normal anti-Ro/SSA IgG increased the specific anti-Ro/SSA binding by greater than 17-fold. This purified antibody formed a Ro/SSA precipitin and had a relative affinity for Ro/SSA identical to that of Ro/SSA precipitin-positive patients. These data demonstrate that the anti-Ro/SSA present in healthy normal donors is true autoantibody. Anti-La/Sjögren's syndrome B antigen (SSB) autoantibodies were found in 3 of the 40 normal sera, while none bound nuclear ribonucleoprotein (Sm). Finding low levels of anti-Ro/SSA and anti-La/SSB among normals may indicate that anti-Ro/SSA and anti-La/SSB occur in disease by enhancement of a preexisting immune response.