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HLA Markers for Susceptibility and Expression in Scleroderma
DAFNA D. GLADMAN, TABITHA N. KUNG, FOTIOS SIANNIS, FAWNDA PELLETT, VERNON T. FAREWELL, and PETER LEE
ABSTRACT. Methods. Consecutive patients were followed in the scleroderma clinic between 1996 and 1998. Clinical data were obtained through chart review. Healthy volunteers as well as cadaveric donors served as controls. Molecular HLA typing was performed (polymerase chain reaction/sequence-specific oligonucleotides). Statistical analysis included Fisher's exact test and multivariate analyses, using logistic and linear regression models. Results. Ninety-five Caucasian patients (75 women, 20 men, age 43.9 yrs, disease duration 11.9 yrs) with scleroderma and 416 controls were studied. HLA-DRB1*01 and HLA-DRB1*11 were associated with susceptibility to scleroderma, whereas HLA-DRB1*07 was protective. HLA-A*30 and HLA-A*32 were also associated with susceptibility to scleroderma, while HLA-B*57 and HLA-Cw*14 were protective. HLA-B*62 and HLA-DRB1*07 had a significant correlation with the presence of diffuse skin involvement in both univariate and multivariate analyses. HLA-DRB1*11 was associated with high skin score values, while lower values were related to the presence of HLA-Cw*14 and HLA-DQB1*06. Both alleles retained significance in a linear regression model. High skin score values were related to the absence of anticentromere antibodies. Pulmonary fibrosis was associated with HLA-B*62 and HLA-Cw*0602, whereas pulmonary hypertension was associated with HLA-B*13 and HLA-B*65. Conclusion. HLA alleles play a role in susceptibility to scleroderma and its disease expression. (J Rheumatol 2005;32:1481-7) Key Indexing Terms:
SCLERODERMA
From the Centre for Prognosis Studies in the Rheumatic Diseases, University Health Network, Toronto Western Hospital, Toronto, Ontario, Canada; MRC Biostatistics Unit, Institute of Public Health, Cambridge, UK; Scleroderma Clinic, Mount Sinai Hospital/University Health Network, Toronto, Canada. D.D. Gladman, MD, FRCPC, Professor of Medicine, University of Toronto, Deputy Director, Centre for Prognosis Studies in the Rheumatic Diseases; T.N. Kung, BSc, Medical Student, University of Toronto; F. Siannis, PhD, Research Associate, MRC Biostatistics Unit, Institute of Public Health; F. Pellett, BSc, Research Technologist, Centre for Prognosis Studies in the Rheumatic Diseases HLA Laboratory; V.T. Farewell, PhD, Senior Scientist, MRC Biostatistics Unit, Institute of Public Health; P. Lee, MD, FRCPC, Professor of Medicine, University of Toronto, Director, Scleroderma Clinic, Mount Sinai Hospital/University Health Network. Address reprint requests to Dr. D.D. Gladman, Toronto Western Hospital, 1E-410B, Toronto, Ontario M5T 2S8. E-mail: dafna.gladman@utoronto.ca Accepted for publication March 14, 2005. |