Early events in lupus humoral autoimmunity suggest initiation through molecular mimicry.
The origins of autoimmunity in systemic lupus erythematosus (SLE) are thought to involve both genetic and environmental factors. To identify environmental agents that could potentially incite autoimmunity, we have traced the autoantibody response in human SLE back in time, prior to clinical disease onset, and identified the initial autoantigenic epitope for some lupus patients positive for antibodies to 60 kDa Ro. This initial epitope directly cross-reacts with a peptide from the latent viral protein Epstein-Barr virus nuclear antigen-1 (EBNA-1). Animals immunized with either the first epitope of 60 kDa Ro or the cross-reactive EBNA-1 epitope progressively develop autoantibodies binding multiple epitopes of Ro and spliceosomal autoantigens. They eventually acquire clinical symptoms of lupus such as leukopenia, thrombocytopenia and renal dysfunction. These data support the hypothesis that some humoral autoimmunity in human lupus arises through molecular mimicry between EBNA-1 and lupus autoantigens and provide further evidence to suspect an etiologic role for Epstein-Barr virus in SLE.
McClain
Micah T
MT
Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, Oklahoma 73104, USA.
Heinlen
Latisha D
LD
Dennis
Gregory J
GJ
Roebuck
Jon
J
Harley
John B
JB
James
Judith A
JA
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D018716:Molecular Mimicry / Q000276:immunology*; D012261:Ribonucleoproteins / Q000276:immunology; D000099207:SS-A Antigen
D000974:Antibodies, Antinuclear; D019309:Epstein-Barr Virus Nuclear Antigens; D012261:Ribonucleoproteins; D000099207:SS-A Antigen; C035356:SS-A antibodies; C417029:EBV-encoded nuclear antigen 1