RT Journal Article
SR Electronic
T1 Autoantibodies that stabilize U1snRNP are a significant component of human autoantibodies to snRNP and delay proteolysis of sm antigens in vitro.
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 2382
OP 2389
VO 31
IS 12
A1 Minoru Satoh
A1 Jun Akaogi
A1 Yoshiki Kuroda
A1 Dina C Nacionales
A1 Hideo Yoshida
A1 Yoshioki Yamasaki
A1 Westley H Reeves
YR 2004
UL http://www.jrheum.org/content/31/12/2382.abstract
AB OBJECTIVE: Autoantibodies to U1-C have been considered a minor component of anti-snRNP (nRNP, Sm) response based on Western blotting. However, we have previously shown that virtually all human anti-nRNP sera contain antibodies to native U1-C, as well as novel autoantibodies that stabilize the molecular interaction of the U1-C-Sm core particle. The biological significance of stabilizing antibodies was investigated by titering anti-U1-C/U1-A compared to stabilizing antibodies, and by examining the effects of stabilizing antibodies on antigen processing. METHODS: Autoantibodies to individual native components of U1snRNP (immunoprecipitation of RNase-treated cell extract) and stabilizing antibodies (dissociation of snRNP on anti-Sm monoclonal antibodies by 1 M MgCl2) in human autoimmune sera were titered. Effects of stabilizing antibodies on proteolysis were assessed by incubating UsnRNP with anti-snRNP/Sm autoimmune sera prior to protease digestion. RESULTS: Autoantibodies to native U1-C and U1-C-Sm core particle stabilizing antibodies were universally present in human anti-nRNP or anti-nRNP + anti-Sm sera, but not in anti-Sm sera. Antibodies to U1-A were less common. The titers of stabilizing antibodies were higher than those of antibodies to U1-C (p < 0.01), indicating that the stabilizing antibodies were a significant component of the anti-snRNP response. The stabilizing anti-nRNP, but not anti-Sm antibodies, protects the Sm core particle from dissociation and proteolysis. CONCLUSION: Autoantibodies stabilizing the U1-C-Sm core particle were universally present in anti-nRNP sera and delay proteolysis of the Sm core particle. They may suppress spreading of the autoimmune response to Sm by delaying or altering processing of the Sm core proteins by antigen-presenting cells.