Autoantibodies That Stabilize U1snRNP Are a Significant Component of Human Autoantibodies to snRNP and Delay Proteolysis of Sm Antigens in Vitro

MINORU SATOH, JUN AKAOGI, YOSHIKI KURODA, DINA C. NACIONALES, HIDEO YOSHIDA, YOSHIOKI YAMASAKI, and WESTLEY H. REEVES

ABSTRACT.

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. (J Rheumatol 2004;31:2382-9)

Key Indexing Terms:

AUTOANTIBODIES
ANTINUCLEAR ANTIBODIES
LUPUS
snRNP
ANTI-Sm ANTIBODIES

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From the Division of Rheumatology and Clinical Immunology, Department of Medicine, and the Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, Florida, USA.

Supported by National Institutes of Health grants R01-AR40391 and M01R00082.

M. Satoh, MD, PhD, Research Associate Professor, Department of Medicine and Department of Pathology, Immunology, and Laboratory Medicine; J. Akaogi, MD, PhD, Research Associate; Y. Kuroda MD, PhD, Research Associate; D.C. Nacionales, MD, Research Associate; H. Yoshida MD, PhD, Research Associate; Y. Yamasaki, MD, Research Associate, Department of Medicine; W.H. Reeves, MD, Marcia Whitney Schott Professor of Medicine and Chief, Division of Rheumatology and Clinical Immunology, Department of Medicine, and Department of Pathology, Immunology, and Laboratory Medicine.

Address reprint requests to Dr. M. Satoh, Division of Rheumatology and Clinical Immunology, University of Florida, PO Box 100221, Gainesville, FL 32610-0221, USA. E-mail: satohm@medicine.ufl.edu

Submitted January 22, 2004; revision accepted July 13, 2004.

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