1429 Tsai, et al: MBL in pediatric SLE Personal non-commercial use only. The Journal of Rheumatology Copyright © 2011. All rights reserved. Mannose-binding Lectin Expression Genotype in Pediatric-onset Systemic Lupus Erythematosus: Associations with Susceptibility to Renal Disease and Protection Against Infections YI-CHAN TSAI, KOU-WEI YEH, TSUNG-CHIEH YAO, YU-LIN HUANG, MING-LING KUO, and JING-LONG HUANG ABSTRACT. Objective. To study possible associations between extended mannose-binding lectin (MBL) expres- sion genotypes and clinical manifestations and infections in children with systemic lupus erythematosus (SLE). Methods. Clinical and laboratory variables for a cohort of 125 patients with pediatric-onset SLE were obtained by clinical examinations and chart reviews. Controls were 137 age-matched and sex-matched healthy children and adolescents. MBL gene polymorphisms were genotyped by poly- merase chain reaction. Serum MBL concentrations were measured by ELISA. Results. The frequencies of extended MBL expression genotypes did not differ between patients and controls. There were 82 patients with SLE who had high MBL expression genotypes and 43 who had medium and low MBL expression genotypes. Patients with the high MBL expression genotype had renal disorders more frequently than patients in the group with medium and low MBL expression genotypes [54/82 (65.9%) vs 18/43 (41.9%), respectively; p = 0.013] and fewer serious bacterial infections [22/82 (26.8%) vs 20/43 (46.5%); p = 0.030]. Using logistic regression for patients with SLE, a high MBL expression genotype was independently associated with renal disorders (OR 2.49, 95% CI 1.15–5.39, p = 0.021) and had a protective effect against serious bacterial infections (OR 0.29, 95% CI 0.12–0.71, p = 0.007). MBL levels decreased significantly when patients with active SLE reached an inactive stage (1.56 ± 0.55 µg/ml vs 1.08 ± 0.65 µg/ml; p = 0.001), but these levels were still higher than those in controls. Conclusion. Our findings suggest that a high MBL expression genotype is a risk factor for renal dis- order, while it has a protective effect against infections. Serum MBL levels reflect SLE activity. (First Release May 1 2011; J Rheumatol 2011;38:1429–35; doi:10.3899/jrheum.100961) Key Indexing Terms: SYSTEMIC LUPUS ERYTHEMATOSUS MANNOSE-BINDING LECTIN PEDIATRIC NEPHRITIS INFECTION From the Department of Pediatrics, Chang Gung Memorial Hospital, Chia-Yi; College of Medicine, Chang Gung University; Chang Gung Institute of Technology; and Department of Microbiology and Immunology, Graduate Institute of Basic Medical Sciences, Chang Gung University, Taoyuan, Taiwan. Supported by a Chang Gung Medical Research Progress Grant (CMRPG 460031) and National Science Council Grants (NSC 95-2314-B-182A-172-MY3 and NSC 98-2314-B-182-002-MY3). Y-C. Tsai, MD, Department of Pediatrics, Chang Gung Memorial Hospital, Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, and Chang Gung Institute of Technology; K-W. Yeh, MD, Assistant Professor, Department of Pediatrics, Chang Gung Memorial Hospital and Chang Gung University; T-C. Yao, MD, PhD, Associate Professor, Department of Pediatrics, Chang Gung Memorial Hospital and Chang Gung University; Y-L. Huang, MD, Department of Pediatrics, Chang Gung Memorial Hospital and Chang Gung University; M-L. Kuo, PhD, Associate Professor, Department of Microbiology and Immunology, Graduate Institute of Basic Medical Sciences, Chang Gung University; J-L. Huang, MD, Professor, Department of Pediatrics, Chang Gung Memorial Hospital and Chang Gung University. Address correspondence to Dr. J.L. Huang, Division of Allergy, Asthma and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, 5 Fu-Hsin Street, Kueishan, Taoyuan, Taiwan. E-mail: long@adm.cgmh.org.tw Accepted for publication February 10, 2011. Mannose-binding lectin (MBL), a component of the com- plement system, plays an important role in innate host defense. Serum MBL can directly opsonize microorganisms and enhance their uptake by phagocytic cells by activation of the lectin pathway of the complement system 1 . In addi- tion, it has been suggested that MBL modulates inflamma- tion and autoimmune diseases 2,3 . Six single-nucleotide polymorphisms (SNP) in the promoter and structural region of the human MBL gene on chromosome 10q are known to influence plasma levels of MBL. Individuals who are heterozygous or homozygous for SNP in codons 52 (allele D, rs5030737), 54 (allele B, rs1800450), or 57 (allele C, rs1800451) in exon 1 of the MBL gene have structural changes that lead to reduced or deficient plasma levels of MBL 2,4 . The wild-type allele is designated A, while the common designation for variant alleles is O. In addition, MBL concentrations fluctuate because of the presence or absence of 3 SNP in the promot- er region of the MBL gene (position –550: alleles H/L, rs11003125; position –221: alleles X/Y, rs7096206; and www.jrheum.org Downloaded on January 17, 2022 from