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Mannose-Binding Lectin is a Disease-Modifying Factor in North American Patients with Systemic Lupus Erythematosus
WENHUA PIAO, CHAU-CHING LIU, AMY H. KAO, SUSAN MANZI, MOLLY T. VOGT, MARGIE J. RUFFING, and JOSEPH M. AHEARN
ABSTRACT. Methods. MBL gene polymorphisms in codons 52 (designated variant D, with the wild-type designated A), 54 (variant B), and 57 (variant C) were determined by polymerase chain reaction-sequence specific priming in 130 patients with SLE and 142 healthy controls. Autoantibodies against double-stranded DNA (dsDNA), Smith antigen, phospholipids, Ro/SSA, La/SSB, and RNP were tested at certified clinical pathology laboratories. Results. A statistically significant increased likelihood of anti-Smith antibody production was observed in SLE patients with the heterozygous A/B genotype [odds ratio (OR) 5.1; 95% confidence interval (CI) 1.6–16.6; the A/A genotype as the reference group] or A/C genotype (OR 8.2; 95% CI 2.0–33.9). SLE patients with the homozygous or compound heterozygous variant genotype (O/O; O, a common designation for variant alleles) had an increased likelihood of mounting autoantibody responses against dsDNA, Ro/SSA, and La/SSB, and were more likely to have a history of renal disease (OR 4.8; 95% CI 0.9–25.2). However, differences in the frequencies of MBL variant alleles and genotypes observed between patients with SLE and controls did not reach statistical significance. Conclusion. A significantly increased prevalence of anti-Smith antibody was associated with the heterozygous genotypes A/B and A/C. Although MBL structural gene polymorphism was not a risk factor for SLE development in this study population, homozygosity of MBL variant alleles may be a weak disease-modifying factor, particularly for renal involvement, in North American patients with SLE. (First Release June 15 2007; J Rheumatol 2007;34:1506-13) Key Indexing Terms:
MANNOSE-BINDING LECTIN
From the Lupus Center of Excellence, University of Pittsburgh Schools of Health Sciences; Graduate School of Public Health, University of Pittsburgh; and Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. Supported by grants from the National Institutes of Health (RO1 HL-074335, RO1 AR-4676402, RO1 AR-46588, NCRR/GCRC MO1-RR-00056, K24 AR-02213, K23 AR-051044), the Lupus Foundation of Pennsylvania, the Alliance for Lupus Research, the Lupus Foundation of Southeastern Pennsylvania, and the Arthritis Foundation. W. Piao, MD; C-C. Liu, MD, PhD; M.J. Ruffing, CCRC; J.M. Ahearn, MD, Lupus Center of Excellence and Division of Rheumatology and Clinical Immunology; A.H. Kao, MD, MPH; S. Manzi, MD, MPH, Lupus Center of Excellence, Graduate School of Public Health, and Division of Rheumatology and Clinical Immunology; M.T. Vogt, PhD, Division of Rheumatology and Clinical Immunology, University of Pittsburgh. Address reprint requests to Dr. J.M. Ahearn, University of Pittsburgh Schools of Health Sciences, Lupus Center of Excellence, 705 Biomedical Science Tower, 3500 Terrace Street, Pittsburgh, PA 15261. E-mail: joa8+@pitt.edu Accepted for publication February 19, 2007. |
