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HLA Class II Alleles in Systemic Sclerosis Patients with Anti-RNA Polymerase I/III Antibody: Associations with Subunit Reactivities
MASATAKA KUWANA, JANARDAN P. PANDEY, RICHARD M. SILVER, YUTAKA KAWAKAMI, and JUNICHI KABURAKI
ABSTRACT.
Methods. HLA-DRB1, DRB3, DRB4, and DQB1 alleles were determined using polymerase chain reaction-based methods in 257 SSc patients (129 Japanese and 128 Caucasians) and 271 race-matched regional controls (138 Japanese and 133 Caucasians). Anti-RNAP I/III antibodies were identified by immunoprecipitation assay, and reactivities to individual RNAP subunits were determined by immunoblots using affinity-purified RNAP I, II, and III. Results. Serum anti-RNAP I/III antibody was detected in 10 (8%) Japanese and 24 (19%) Caucasian patients with SSc. The presence of anti-RNAP I/III antibodies was associated with DRB1*0405, DRB4*01, and DQB1*0401 in Japanese, and with DRB3*02 in Caucasians, but these associations were weak and inconsistent between these 2 ethnic groups. When anti-RNAP I/III-positive SSc patients were divided into 2 groups based on the presence or absence of reactivities to individual RNAP subunit proteins, significant associations of anti-IIa/IIo reactivity with DRB3*02, anti-Ia reactivity with DRB1*04, anti-43-kDa subunit reactivity with DRB4*01, and anti-34-kDa subunit reactivity with DRB1*15 were detected. These HLA associations with subunit reactivities were generally shared by Japanese and Caucasian patients with SSc. Conclusion. Our results suggest that in patients with SSc, anti-RNAP I/III antibodies are composed of subsets defined by combinations of reactivities to individual RNAP subunits having specific HLA class II correlations. (J Rheumatol 2003;30:2392-7 Key Indexing Terms:
AUTOANTIBODY
From the Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan; the Department of Microbiology and Immunology and Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA; and Department of Internal Medicine, Tokyo Electric Power Company Hospital, Tokyo, Japan. Supported in part by grants from the Ministry of Health, Labour, and Welfare in Japan, and the US Department of Energy cooperative agreement DE-FC02-02CH11109. M. Kuwana, MD; Y. Kawakami, MD, Keio University School of Medicine; J.P. Pandey, PhD; R.M. Silver, MD, Medical University of South Carolina; J. Kaburaki, MD, Tokyo Electric Power Company Hospital. Address reprint requests to Dr. M. Kuwana, Institute for Advanced Medical Research, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. E-mail: kuwanam@sc.itc.keio.ac.jp Submitted January 15, 2003; revision accepted April 17, 2003. |