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Elevated Levels of Mannose-Binding Lectin at Clinical Manifestation of Type 1 Diabetes in Juveniles

¹ Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands
² Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands
³ Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands
⁴ Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands
⁵ Department of Clinical Chemistry, Leiden University Medical Center, Leiden, the Netherlands
⁶ Sophia Children’s Hospital, Erasmus University Medical Center, Rotterdam, the Netherlands

Mannose-binding lectin (MBL) is a recognition molecule of the lectin pathway of complement and a key component of innate immunity. MBL polymorphisms have been described that are associated with MBL serum concentration, impaired function, and diabetic complications. We investigated 86 new-onset juvenile type 1 diabetic patients and compared these with their nondiabetic siblings and healthy unrelated control subjects. Polymorphisms of MBL exon 1 and promoter were determined, and serum concentration and MBL-complex activity were measured. Although the genetic polymorphisms of MBL were not different between patients and control subjects, MBL serum concentration as well as MBL complex activity was significantly higher in new-onset diabetic patients compared with their siblings matched for high-producing MBL genotypes (P = 0.0018 and P = 0.0005, respectively). The increase in MBL complex activity in high-MBL–producing patients could only partially be explained by high MBL production, as demonstrated by an increased MBL complex activity–to–MBL concentration ratio (P = 0.004). We conclude that MBL serum concentration and complex activity are increased in early- onset diabetic patients upon manifestation independently of genetic predisposition to high MBL production, indicating a possible role in the immunopathogenesis of type 1 diabetes, in addition to the adaptive islet autoimmunity.

Abbreviations: CRP, C-reactive protein; mAb, monoclonal antibody; MASP, mannose-binding lectin-associated serine protease; MBL, mannose-binding lectin; SNP, single nucleotide polymorphism

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