Bouwman LH, Roep BO, Roos AMannose-binding lectin: clinical implications for infection, transplantation, and autoimmunity. Hum Immunol 67:247-256

Leiden University, Leyden, South Holland, Netherlands
Human Immunology (Impact Factor: 2.14). 04/2006; 67(4-5):247-56. DOI: 10.1016/j.humimm.2006.02.030
Source: PubMed


Mannose-binding lectin (MBL) is a recognition molecule of the lectin pathway of complement and a key component of innate immunity. MBL variant alleles have been described in the coding region of the MBL gene, which are associated with low MBL serum concentration and impaired MBL structure and function. Both high and low serum levels of functional MBL have been associated with a variety of diseases and disease complications. Functioning as double-edged sword, low MBL serum levels have been shown to enhance the risk for infections. On the other hand, high MBL serum levels and high MBL activity have been associated with inflammatory diseases, transplant rejection, and diabetic nephropathy. Underscoring the Jekyll-and-Hyde character of MBL, both high and low serum MBL levels are associated with several aspects of autoimmune diseases. This review provides a general outline of the genetic and molecular characteristics of MBL and discusses MBL-disease association and its consequence in infection, transplantation, and autoimmunity.

Download full-text


Available from: Bart Roep,
  • Source
    • "c o m / l o c a t e / h u m i m m activate the functional responses of human neutrophils [1] [2] [4]. The description of molecular features of FccR [5] and CR [6] [7] has improved comprehension of the effector functions of human neutrophils triggered via these receptors, but the specific role of polymorphic variants remains unclear. The binding of IgG to FccR induces a wide range of biological responses [3], which provides an important link between cellular and humoral immunity. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Considering that human neutrophil FcγRIIa and FcγRIIIb receptors interact synergistically with CR3 in triggering neutrophil functional responses, allelic polymorphisms in these receptors might influence such interactions. We assessed whether FcγRIIIb polymorphisms affect FcγR/CR cooperation in mediating the neutrophil oxidative burst (OB), in particular the FcγRIIIb/CR3 cooperation that occurs via lectin-saccharide-like interactions. The OB of human neutrophil antigen (HNA)-1a-, HNA-1b-, and HNA-1a/-1b-neutrophils stimulated with immune complexes, opsonized or not with serum complement, was measured by the luminol-enhanced chemiluminescence assay. Compared with HNA-1a-neutrophils, HNA-1b-neutrophils exhibited reduced FcγR-stimulated OB, but increased FcγR/CR-stimulated OB. It suggests that (i) FcγR and CR cooperate more effectively in HNA-1b-neutrophils, and (ii) the HNA-1b allotype influences the FcγRIIIb cooperation with FcγRIIa, but not with CR3. HNA-1a- and HNA-1b-neutrophils exhibited similar OB responses elicited via CR3 alone or via FcγR/CR-independent pathways. In addition, the level of FcγRIIIb, FcγRIIa, and CR3 expression did not differ significantly among the neutrophil groups studied. Together, these results demonstrate that the HNA-1b allotype influences the functional cooperation between FcγRIIIb and FcγRIIa, and suggest that the difference in the glycosylation pattern between HNA-1a and HNA-1b does not affect the FcγRIIIb cooperation with CR3.
    Human immunology 08/2014; DOI:10.1016/j.humimm.2014.05.011 · 2.14 Impact Factor
  • Source
    • "High levels of MBL, might result in excessive component activation and prime adaptive immune response, but on the other hand suppress cytokine release (Jack et al., 2001; Wang et al., 2011). Low levels of MBL might enhance adaptive autoimmune response, because of impaired clearance of apoptotic and necrotic cells (Bouwman et al., 2006; Nauta et al., 2003) and enhanced cytokine release (Jack et al., 2001). One previous, relatively small, study has shown association between high producing MBL genotypes and MBL-complex activity , with the development of T1D (Bouwman et al., 2005). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The incidence of type 1 diabetes (T1D) has during the last few decades been increasing in children and juveniles. Multi-factorial courses combining genetic disposition and environmental factors might be in play, and through the years, there has been a mounting interest in the innate immune system's role in the development of T1D. The aim of this study was to determine mannose binding lectin (MBL) levels in newly diagnosed children with T1D (n=481) over a period of 10 years (1997-2005) and to compare these levels with corresponding levels in their healthy siblings (n=479). Furthermore, the aims were to evaluate if MBL-levels in patients and siblings were influenced by season, age autoimmunity and/or changed over time. The study found that MBL levels differed between patients and their healthy siblings when adjusted for age, gender, season and period. More patients than siblings had MBL levels above 0.8μg/ml, associated with high producing MBL genotypes, and the elevated MBL levels were associated with high levels of four T1D related cytokines (IL-1β, IL-12, IL-18 and TNF-α). MBL levels increased during the study period and siblings had seasonal variance in concentrations with the lowest level during wintertime (Dec-Feb). In conclusion, more patients than siblings had a high MBL level, and high levels of MBL were related to high levels of T1D specific cytokines, supporting a role of the innate immune system and MBL on the risk of developing T1D.
    Molecular Immunology 06/2014; 62(1):71-76. DOI:10.1016/j.molimm.2014.06.001 · 2.97 Impact Factor
  • Source
    • "It is one of the recognition molecules in the lectin complement activation pathway [6]. Human MBL is derived from a single gene located on chromosome 10 (MBL2) [3-8]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Serious infections are common in patients undergoing autologous stem cell transplantation (ASCT) mainly because of the effects of immunosuppression. The innate immune system plays an important role in the defense against different infections. Mannose binding lectin (MBL) is a central molecule of the innate immune system. There are several promoter polymorphisms and structural variants of the MBL2 gene that encodes for this protein. These variants produce low levels of MBL and have been associated with an increased risk for infections. Methods Prospective cohort study. The incidence, severity of infections and mortality in 72 consecutive patients with hematologic diseases who underwent ASCT between February 2006 and June 2008 in a tertiary referral center were analyzed according to their MBL2 genotype. INNO-LiPA MBL2 was used for MBL2 gene amplification and genotyping. Relative risks (RR) (IC95%) as measure of association were calculated. Multivariate analysis was performed using logistic regression. Results A statistically significant higher number of fungal infections was found in patients with MBL2 variants causing low MBL levels (21.1%versus1.9%, p=0.016). In this MBL2 variant group infection was more frequently the cause of mortality than in the MBL2 wild-type group (p=0.05). Although not statistically significant, there was a higher incidence of major infections in the MBL2 variant group as well as a higher number of infections caused by gram-positive bacteria. Conclusions Low-producer MBL2 genotypes were associated with an increased number of fungal infections in ASCT patients, which would suggest that MBL has a protective role against such infections. ASCT patients with MBL2 variant genotypes are more likely to die as a result of an infection.
    BMC Immunology 05/2014; 15(1):17. DOI:10.1186/1471-2172-15-17 · 2.48 Impact Factor
Show more