The authors declare that they have no competing interests.
AM participated in data collection and manuscript preparation. CF-A participated in the design of the study, performed the statistical analysis and reviewed and revised the manuscript. MP participated in collection of data and manuscript preparation. JGO-V carried out part of the MBL2 genotyping, and revised the manuscript. PS-V carried out part of the MBL2 genotyping and revised the manuscript. JPH participated in the design of the study and reviewed and revised the manuscript. AB participated in collection of data. CM participated in collection of data and manuscript preparation. FS participated in collection of data and manuscript preparation. EC reviewed and revised the manuscript. MCF: participated in the design of the study, data analysis and reviewed and revised the manuscript. All authors read and approved the final manuscript.
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.
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.
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.
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.
Schimpff SC: Empiric antibiotic therapy for granulocytopenic cancer patients. Am J Med. 1986, 80 (Suppl. 5C): 13-20. PubMed
Sastry K, Herman GA, Day L, Deignan E, Bruns G, Morton CC, Ezekowitz RA: The human mannose-binding protein gene. Exon structure reveals its evolutionary relationship to a human pulmonary surfactant gene and localization to chromosome 10. J Exp Med. 1989, 170: 1175-1189. 10.1084/jem.170.4.1175. PubMedCrossRef
Vekemans M, Robinson J, Georgala A, Heymans C, Muanza F, Paesmans M, Klastersky J, Barette M, Meuleman N, Huet F, Calandra T, Costantini S, Ferrant A, Mathissen F, Axelsen M, Marchetti O, Aoun M: Low mannose-binding lectin concentration is associated with severe infection in patients with hematological cancer who are undergoing chemotherapy. Clin Infect Dis. 2007, 44 (12): 1593-1601. 10.1086/518171. PubMedCrossRef
Osthoff M, Rovó A, Stern M, Danner D, Gratwohl A, Tichelli A, Trendelenburg M: Mannose-binding lectin levels and major infections in a cohort of very long-term survivors after allogenic stem cell transplantation. Haematologica. 2010, 95: 1389-1396. 10.3324/haematol.2009.017863. PubMedPubMedCentralCrossRef
Mullighan CG, Heatley SL, Danner S, Dean MM, Doherty K, Hahn U, Bradstock KF, Minchinton R, Schwarer AP, Szer J, Bardy PG: Mannose-binding lectin status is associated with risk of major infection following myeloablative sibling allogeneic hematopoietic stem cell transplantation. Blood. 2008, 112: 2120-2128. 10.1182/blood-2007-07-100222. PubMedCrossRef
Granell M, Urbano-Ispizua A, Suarez B, Rovira M, Fernández-Avilés F, Martínez C, Ortega M, Uriburu C, Gaya A, Roncero JM, Navarro A, Carreras E, Mensa J, Vives J, Rozman C, Montserrat E, Lozano F: Mannan-binding lectin pathway deficiencies and invasive fungal infections following allogeneic stem cell transplantation. Exp Hematol. 2006, 34: 1435-1441. 10.1016/j.exphem.2006.06.005. PubMedCrossRef
Rocha V, Franco RF, Porcher R, Bittencourt H, Silva WA, Latouche A, Devergie A, Esperou H, Ribaud P, Socie G, Zago MA, Gluckman E: Host defense and inflammatory gene polymorphisms are associated with outcomes after HLA-identical sibling bone marrow transplantation. Blood. 2002, 100: 3908-3018. 10.1182/blood-2002-04-1033. PubMedCrossRef
Mullighan CG, Heatley S, Doherty K, Szabo F, Grigg A, Hughes TP, Schwarer AP, Szer J, Tait BD, Bik To L, Bardy PG: Mannose-binding lectin gene polymorphisms are associated with major infection following allogeneic hemopoietic stem cell transplantation. Blood. 2002, 99: 3524-3529. 10.1182/blood.V99.10.3524. PubMedCrossRef
Horiuchi T, Gondo H, Miyagawa H, Otsuka J, Inaba S, Nagafuji K, Takase K, Tsukamoto H, Koyama T, Mitoma H, Tamimoto Y, Miyagi Y, Tahira T, Hayashi K, Hashimura C, Okamura S, Harada M: Association of MBL gene polymorphisms with major bacterial infection in patients treated with high-dose chemotherapy and autologous PBSCT. Genes Immun. 2005, 6: 162-166. 10.1038/sj.gene.6364165. PubMedCrossRef
IDSA clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer. Available from: http://www.idsociety.org/Antimicrobial_Agents/#Neutropenic%20Patients%20with%20Cancer (Accesed on 13 February 2013)
Hellemann D, Larsson A, Madsen HO, Bonde J, Jarløv JO, Wiis J, Faber T, Wetterslev J, Garred P: Heterozygosity of mannose-binding lectin (MBL2) genotypes predicts advantage (heterosis) in relation to fatal outcome in intensive care patients. Hum Mol Genet. 2007, 16: 3071-3080. 10.1093/hmg/ddm265. PubMedCrossRef
- Mannose-binding lectin gene variants and infections in patients receiving autologous stem cell transplantation
Javier Gonzalo Ocejo-Vinyals
Juan Pablo Horcajada
- BioMed Central
Neu im Fachgebiet Innere Medizin
Meistgelesene Bücher aus der Inneren Medizin
Mail Icon II