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Relationships Between Autoantibody Responses to Deletion Mutants of Ki Antigen and Clinical Manifestations of Lupus
RAN MATSUDAIRA, KEN TAKEUCHI, YOSHINARI TAKASAKI, TETSURO YANO, MASAKAZU MATSUSHITA, and HIROSHI HASHIMOTO
ABSTRACT. Objective. To determine the relationships between subtypes of anti-Ki antibodies and clinical manifestations of systemic lupus erythematosus. Methods. The cDNA encoding full-length bovine Ki antigens or N- or C-terminal fragments were produced by polymerase chain reaction, and the fragments of Ki antigen were expressed as GST fusion proteins. Immunoreactivities of anti-Ki antibodies were tested by Western blotting. Results. Of 60 sera reactive with full-length Ki antigen (KiF), 21 sera recognized only KiF. KiC5, a fragment containing the last 69 C-terminal amino acids, was recognized by 23 sera. Since no significant difference was observed in prevalence of reactivities between fragments from KiC2 to KiC5, a domain within the last 69 C-terminal amino acids was suggested to be the most common antigenic domain expressed among the GST fusion proteins. All 11 sera reacting with a fragment containing the initial 81 N-terminal amino acids also recognized all other fragments. A domain homologous to SV40 nuclear localization signal was required for N-terminal recognition by 8 sera. Reactivity to the last 69 C-terminal amino acids and the initial 81 N-terminal amino acids showed specificities to systemic lupus erythematosus without and with Sjögren's syndrome, respectively. Sicca was significantly more prevalent in patients whose sera reacted with both N- and C-terminal fragments, while prevalence of anti-SSA/Ro antibody was low. Conclusion. Ki antigen contains multiple epitopes recognized by autoimmune sera. Autoantibody profiles revealed distinctive immune responses, associated with certain clinical subtypes. (J Rheumatol 2003;30:1208-14) Key Indexing Terms:
ANTI-KI ANTIBODY
From the Department of Internal Medicine and Rheumatology, Juntendo University, School of Medicine, Tokyo, Japan. Supported by a grant-in-aid for scientific research (no. 13670474) from the Ministry of Education, Science, and Culture of Japan. R. Matsudaira, MD, Postgraduate; K. Takeuchi, MD, PhD, Lecturer; Y. Takasaki, MD, PhD, Associate Professor; T. Yano, MD, PhD, Assistant Professor; M. Matsushita, MD, Assistant Professor; H. Hashimoto, MD, PhD, Professor. Address reprint requests to Dr. K. Takeuchi, Department of Internal Medicine and Rheumatology, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113 –8421, Japan. E-mail: ranmatsu@cronos.ocn.ne.jp Submitted June 25, 2002; revision accepted November 18, 2002. |