60 kD Ro and nRNP A frequently initiate human lupus autoimmunity

• Published in: PloS one 2010-03, Vol.5 (3), p.e9599
• Main Authors: Heinlen, Latisha D, McClain, Micah T, Ritterhouse, Lauren L, Bruner, Benjamin F, Edgerton, Colin C, Keith, Michael P, James, Judith A, Harley, John B
• Format: Article
• Language: English
• Subjects: Antibodies; Antigenic determinants; Antigens; Arthritis; Autoantibodies; Autoantigens - blood; Autoantigens - chemistry; Autoimmune diseases; Autoimmunity; Blood lipids; Case-Control Studies; Chronic conditions; Diagnostic systems; Epitopes; Epitopes - chemistry; Female; Health sciences; HeLa Cells; Humans; Illnesses; Immunoassay; Immunoglobulins; Immunology; Immunology/Antigen Processing and Recognition; Immunology/Autoimmunity; Internal medicine; Lupus; Lupus Erythematosus, Systemic - blood; Lupus Erythematosus, Systemic - immunology; Male; Medical research; Medicine; Membrane lipids; Pathogenesis; Pathology; Patients; Pattern recognition; Peptides; Phospholipids; Proteins; Rheumatoid factor; Rheumatology/Autoimmunity, Autoimmune, and Inflammatory Diseases; Rheumatology/Systemic Lupus Erythematosos; Ribonucleoproteins - blood; Ribonucleoproteins - chemistry; Systemic lupus erythematosus
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0009599

Systemic lupus erythematosus (SLE) is a clinically heterogeneous, humoral autoimmune disorder. The unifying feature among SLE patients is the production of large quantities of autoantibodies. Serum samples from 129 patients collected before the onset of SLE and while in the United States military were evaluated for early pre-clinical serologic events. The first available positive serum sample frequently already contained multiple autoantibody specificities (65%). However, in 34 SLE patients the earliest pre-clinical serum sample positive for any detectable common autoantibody bound only a single autoantigen, most commonly 60 kD Ro (29%), nRNP A (24%), anti-phospholipids (18%) or rheumatoid factor (15%). We identified several recurrent patterns of autoantibody onset using these pre-diagnostic samples. In the serum samples available, anti-nRNP A appeared before or simultaneously with anti-nRNP 70 K in 96% of the patients who had both autoantibodies at diagnosis. Anti-60 kD Ro antibodies appeared before or simultaneously with anti-La (98%) or anti-52 kD Ro (95%). The autoantibody response in SLE patients begins simply, often binding a single specific autoantigen years before disease onset, followed by epitope spreading to additional autoantigenic specificities that are accrued in recurring patterns.