1270 The Journal of Rheumatology 2007; 34:6 Personal non-commercial use only. The Journal of Rheumatology Copyright © 2007. All rights reserved. Mannose-Binding Lectin and Susceptibility to Infection in Chinese Patients with Systemic Lupus Erythematosus MOYINMOK,W.K.EDDIEIP,CHAKSINGLAU,YILO,WILFREDH.S.WONG,andYULUNGLAU ABSTRACT. Objective. Totestthehypothesisthatlowserummannose-bindinglectin(MBL)levels,asaresultofthe single-nucleotidepolymorphismsinthepromoterregion(–221X/Y)andexon1(codon54A/B)ofthe MBL2 gene, predispose to infection in Chinese patients with systemic lupus erythematosus (SLE). Methods. Two hundred forty-five patients with SLE were prospectively followed for the development of major infective episodes that required hospitalization and antibiotic treatment during 1992-2005. MBLgenotypesweredeterminedbypolymerasechainreactionandserumMBLlevelsweremeasured by ELISA. Results. Intotal,254majorinfectionsdevelopedin130patients.SerumMBLlevelswereshowntocor- relate inversely with the number of bacterial infections (r = –0.13, p = 0.03). The distribution of MBL genotypeswassimilarinpatientswithandwithoutmajorinfection(p=0.84).Patientswithmajorinfec- tion also had more major lupus exacerbations that required daily prednisolone dose ≥ 15 mg. Logistic regression showed that log MBL level (odds ratio 0.516, 95% confidence interval 0.305–0.873; p = 0.01)andmajorlupusexacerbation(OR1.382,95%CI1.154–1.654;p<0.001)wereindependentrisk factors to major bacterial infection after adjustment for age and disease duration. Multiple regression analysis showed an increase in risk of bacterial infection by 34.2% for every decrease in serum MBL levelbyonelog,andby22.8%foreachincreaseinnumberofmajorlupusexacerbations. Conclusion. Low serum MBL level predisposes Chinese patients with SLE to more major infections, in particular bacterial ones. (J Rheumatol 2007;34:1270–6) Key Indexing Terms: COMPLEMENTDEFICIENCY HOSPITALIZATION IMMUNOCOMPROMISED HOST IMMUNOSUPPRESSANT INFECTION From the Departments of Medicine and Pediatrics and Adolescent Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong. Supported by a University Department of Medicine Grant, University Department of Medicine, Queen Mary Hospital, Hong Kong and Shun Tak District Min Yuen Tong Fund. M.Y. Mok, MD, Rheumatologist, Department of Medicine, Queen Mary Hospital; W.K.E. Ip, PhD, Research Fellow, Laboratory of Developmental Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; C.S. Lau, MD, Professor in Medicine; Y. Lo, Research Assistant, Division of Rheumatology, Department of Medicine; W. Wong, MMedSc, Senior Statistician; Y.L. Lau, MD, Chair, Professor, Department of Pediatrics and Adolescent Medicine, Queen Mary Hospital. Address reprint requests to Dr. M.Y. Mok, Division of Rheumatology, Queen Mary Hospital, Pokfulam Road, Hong Kong. E-mail: mymok@netvigator.com Accepted for publication February 7, 2007. Mannose-binding lectin (MBL) is a serum C-type lectin that plays an important role in innate immunity 1,2 . Upon binding to targets, MBL can activate the complement cascade called lectin pathway via MBL-associated serine proteases 3 . The lectin exhibits antibacterial activity through killing mediated by the terminal lytic complement components or by promot- ing phagocytosis 4,5 . MBL is able to promote opsonization either by activation of complements and generation of C3b fragments via the lectin pathway 6 or by acting directly as an opsonin interacting with surface receptors on phagocytic cells 7,8 . MBL binds to glycoprotein terminated with mannose and N-acetylglucosamine that is present on a variety of microorganisms including bacteria, yeasts, parasitic protozoa, and viruses 6,9-13 . MBL deficiency was first identified in indi- viduals with recurrent infections and having serum defect in opsonophagocytosis 14 . Indeed, MBL deficiency as a result of polymorphismsoftheMBL(MBL2)genehasbeenknownto be associated with frequent infections in children 15,16 , adults 17,18 , and those with immunodeficiency 19,20 . These patients were particularly prone to both gram-positive and gram-negative bacterial infection 21 .Amousemodeldeficient in MBL was also shown to be susceptible to infection by gram-positive bacteria 22 . Beyondinfection,MBLdeficiencyhasalsobeenshownto predispose to autoimmune diseases like systemic lupus ery- thematosus (SLE) 23,24 . Some studies have also suggested a role of MBL as a disease modifier in lupus 25,26 . Mutation of any of the 3 codons 52, 54, and 57 of exon 1 of the MBL2 genehasbeenshowntobeassociatedwithlowMBLlevelsin different ethnic populations 27-29 . Codon 54 mutation (A/B) hasbeenshownbyourgrouptobethemostprevalentformof mutation found in our local Chinese population, with a gene www.jrheum.org Downloaded on January 22, 2022 from