Autoantibodies to heat shock protein 90 in the human natural antibody repertoire.
The present study demonstrates the presence of natural autoantibodies of the IgG isotype directed against heat shock protein 90 (HSP90). The binding properties of affinity-purified anti-HSP antibodies were compared with those of natural antibodies specific for other self antigens, including anti-thyroglobulin and anti-myoglobin autoantibodies, by using semiquantitative immunoblotting, with solubilized proteins from normal liver tissue as antigens, and cross-blot analysis using purified self proteins. Affinity-purified anti-HSP90 antibodies were polyreactive and the non-HSP90-specific fraction of normal IgG was depleted in its natural autoantibody content. We further observed that self antigens including HSP, myosin, tubulin and aldolase with highly conserved structures show similar patterns of binding with natural antibodies, and form a well-defined cluster as demonstrated by cluster analysis of immunoreactivity data, whereas the less-conserved self and non-self antigens remained unclustered. The results favor the hypothesis that HSP90 belongs to a subset of highly conserved and immunodominant self antigens that are the primary target for natural autoantibodies in normal human IgG.
Pashov
Anastas
A
INSERM U430, Hôpital Broussais, 96 rue Didot, 75014 Paris, France.
Kenderov
Andrey
A
Kyurkchiev
Stanimir
S
Kehayov
Ivan
I
Hristova
Svetla
S
Lacroix-Desmazes
Sebastien
S
Giltiay
Natalia
N
Varamballi
Sooryanarayana
S
Kazatchkine
Michael D
MD
Kaveri
Srini V
SV
D000199:Actins / Q000276:immunology; D001323:Autoantibodies / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D001324:Autoantigens / Q000276:immunology; D018841:HSP90 Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology / Q000302:isolation & purification; D007135:Immunoglobulin Variable Region / Q000032:analysis / Q000276:immunology; D009218:Myosins / Q000276:immunology; D012260:Ribonucleases / Q000276:immunology
D000199:Actins; D001323:Autoantibodies; D001324:Autoantigens; D018841:HSP90 Heat-Shock Proteins; D007074:Immunoglobulin G; D007135:Immunoglobulin Variable Region; D012260:Ribonucleases; D009218:Myosins