Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

Mannan-binding lectin deficiency attenuates acute GvHD in pediatric hematopoietic stem cell transplantation

Bone Marrow Transplantation volume 50, pages 1127–1129 (2015)Cite this article

Subjects

Mannan-binding lectin (MBL) is an acute phase protein that is synthesized in the liver and involved in first-line immune defense. Together with MBL-associated serine proteases (MASPs), MBL mediates opsonization and activates the lectin pathway of C'. The MBL gene is highly polymorphic and specific single-nucleotide polymorhism (SNP) patterns define at least 7 common haplotypes, giving 28 genotype possibilities. Exon-1 and/or promoter SNPs affect MBL serum levels and/or function (reviewed in ref. 1). Particular SNPs and/or low serum levels are listed among common human immunodeficiencies but only rarely translate into a severe clinical phenotype.1 Nonetheless, in hematopoietic stem cell transplantation (HSCT), a setting that per se causes a transient but profound state of immunodeficiency, low MBL levels or particular MBL genotypes are reported to contribute to and increase the rate of transplant-related infections.

In consideration of the so far inconsistent findings of the role of MBL in HSCT in adult,2, 3, 4, 5 as well as pediatric6 HSCT, we prospectively investigated the impact of MBL levels, genotypes and MASP-2 levels in a series of 99 pediatric (n=96) and young adult (n=3) HSCT recipients. MBL deficiency was defined by MBL levels <300 ng/mL and/or particular MBL haplotypes. Patient characteristics, MBL genotype data and corresponding MBL levels are summarized in the Supplementary Information together with MASP-2 serum levels and statistical analyses.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

References

  1. Heitzeneder S, Seidel M, Forster-Waldl E, Heitger A . Mannan-binding lectin deficiency—good news, bad news, doesn't matter? Clin Immunol 2012; 143: 22–38.

    Article  CAS  Google Scholar 

  2. Mullighan CG, Heatley SL, Danner S, Dean MM, Doherty K, Hahn U et al. Mannose-binding lectin status is associated with risk of major infection following myeloablative sibling allogeneic hematopoietic stem cell transplantation. Blood 2008; 112: 2120–2128.

    Article  CAS  Google Scholar 

  3. Rocha V, Franco RF, Porcher R, Bittencourt H, Silva WA Jr., Latouche A et al. Host defense and inflammatory gene polymorphisms are associated with outcomes after HLA-identical sibling bone marrow transplantation. Blood 2002; 100: 3908–3918.

    Article  CAS  Google Scholar 

  4. Neth OW, Bacher U, Das P, Zabelina T, Kabisch H, Kroeger N et al. Influence of mannose-binding lectin genotypes and serostatus in Allo-SCT: analysis of 131 recipients and donors. Bone Marrow Transplant 2009; 45: 13–19.

    Article  Google Scholar 

  5. Granell M, Urbano-Ispizua A, Suarez B, Rovira M, Fernandez-Aviles F, Martinez C et al. Mannan-binding lectin pathway deficiencies and invasive fungal infections following allogeneic stem cell transplantation. Exp Hematol 2006; 34: 1435–1441.

    Article  CAS  Google Scholar 

  6. Chaudhry SH, Chaudhry S, Jansen-Hoogendijk AM, Jol van der Zijde CM, van Tol MJ, Roos A et al. Mannose-binding lectin levels and infections in children after allogeneic hematopoietic SCT. Bone Marrow Transplant 2010; 45: 289–293.

    Article  CAS  Google Scholar 

  7. Berger SP, Daha MR . Emerging role of the mannose-binding lectin-dependent pathway of complement activation in clinical organ transplantation. Curr Opin Organ Transplant 2011; 16: 28–33.

    Article  CAS  Google Scholar 

  8. Osthoff M, Katan M, Fluri F, Schuetz P, Bingisser R, Kappos L et al. Mannose-binding lectin deficiency is associated with smaller infarction size and favorable outcome in ischemic stroke patients. PLoS One 2011; 6: e21338.

    Article  CAS  Google Scholar 

  9. Ma Q, Li D, Nurieva R, Patenia R, Bassett R, Cao W et al. Reduced graft-versus-host disease in C3-deficient mice is associated with decreased donor Th1/Th17 differentiation. Biol Blood Marrow Transplant 2012; 18: 1174–1181.

    Article  CAS  Google Scholar 

  10. Ma Q, Li D, Carreno R, Patenia R, Tsai KY, Xydes-Smith M et al. Complement component C3 mediates Th1/Th17 polarization in human T-cell activation and cutaneous GVHD. Bone Marrow Transplant 2014; 49: 972–976.

    Article  CAS  Google Scholar 

  11. Nauta AJ, Raaschou-Jensen N, Roos A, Daha MR, Madsen HO, Borrias-Essers MC et al. Mannose-binding lectin engagement with late apoptotic and necrotic cells. Eur J Immunol 2003; 33: 2853–2863.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We express our gratitude to the nurses of the stem cell transplantation unit and outpatient clinic for collecting the samples and, most of all, to the patients and their parents for supporting the study by giving their informed consent and donating blood. This work was supported in part by a grant from the Austrian National Bank (#13075) and by an Institutional Grant of the CCRI. It is dedicated to our friend, colleague and mentor—AH, who planned and supervised this study and who unexpectedly passed away after finalization of the manuscript.

Author information

Author notes

  1. S Heitzeneder

    Present address: Pediatric Oncology Branch, National Cancer Institute, Bldg 10-CRC, R 1W-3840, 10 Center Dr, Bethesda, MD 20892, USA,

Authors and Affiliations

  1. Transplantation Immunology, Children’s Cancer Research Institute, Vienna, Austria

    S Heitzeneder, U Pötschger, M Hölzl, D Heja, O A Haas & A Heitger

  2. medgen.at GmbH, Vienna, Austria

    P Zeitlhofer & O A Haas

  3. St. Anna Kinderspital, Medical University Vienna, Vienna, Austria

    E Nowak, M G Seidel, A Lawitschka, E Förster-Waldl, S Matthes-Martin, O A Haas & A Heitger

  4. Department of Pediatrics, Medical University Vienna, Vienna, Austria

    E Förster-Waldl

Authors
  1. S Heitzeneder
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P Zeitlhofer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. U Pötschger
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E Nowak
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M G Seidel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M Hölzl
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A Lawitschka
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. E Förster-Waldl
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. S Matthes-Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. D Heja
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. O A Haas
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. A Heitger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S Heitzeneder.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on Bone Marrow Transplantation website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Heitzeneder, S., Zeitlhofer, P., Pötschger, U. et al. Mannan-binding lectin deficiency attenuates acute GvHD in pediatric hematopoietic stem cell transplantation. Bone Marrow Transplant 50, 1127–1129 (2015). https://doi.org/10.1038/bmt.2015.81

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2015.81

Search

Advanced search

Quick links