Laboratory for Pediatric Immunology

Pediatric hematopoietic stem cell therapy

Our research-topics include:

• immune reconstitution after transplantation
• pharmacokinetics of serotherapy and chemotherapy and its relation with immunological reconstitution and clinical outcome
• long term graft function in relation to clinical outcome after hematopoietic stem cell transplantation
• early detection and treatment of graft-versus-host disease
• optimal strategies for disease remission induction prior to transplantation in primary hemophagocytic lymphohistiocytosis
• gene therapy for inborn errors (in close collaboration with The laboratory of Frank Staal)

Newborn screening for severe immunodeficiencies

We work on the implementation and development of new-born screening for severe primary immunodeficiencies. This is done in close collaboration with the RIVM and other stakeholders, such as patient support groups. For the implementation of screening for Severe Combined Immunodeficiency, the SONNET-study was started (www.sonnetstudie.nl). For X-linked agammaglobulinemia the efficacy and judiciousness of newborn screening is evaluated in the study “Geef XLA geen tijd” (www.xla.nu). We are an active member in the Screen4Rare ERN expert platform for NBS (www.screen4rare.org) and lead Workstream 2 on Case definitions for NBS and approaches to confirmatory testing.

B-cell development and primary immunodeficiencies

We study B-cell development in patients with primary immunodeficiencies, after hematopoietic stem cell transplantation and in healthy individuals. We have specific interest in the formation and selection of the B-cell receptor repertoire, the influence of inherited defects and repertoire formation and selection after hematopoietic stem cell transplantation. Moreover, we have a research line on DNA repair disorders, especially Ataxia Telangiectasia for which we collaborate with Radboud UMC. 

Together with clinicians and geneticists of the WAKZ we collaborate on diagnosing children with (suspected) monogenic primary immunodeficiencies.

T and NK cell development and responses

We study the reconstitution of cellular immunity after stem cell transplantation. In addition, we study the responding T cell and NK cell compartment in responses to viral infections. We are also interested in the development of NK cells and the role of tissue-resident immune cells.

Immunogenetics, auto-immunity and immune-dysregulation syndromes

We are studying immunological features and genetic risk factors for SARS-CoV-2 related Multisystem Inflammatory Syndrome in Children (MIS-C) and pediatric post-COVID condition (see www.covidkids.nl/grip).

We are evaluating the immunological profiles of children included in the BeSt for Kids -study, a treat-to-target study in juvenile idiopathic arthritis.

Bone marrow failure syndromes and severe aplastic anemia

The focus of our research in pediatric bone marrow failure is to determine the etiology in individual patients using a standardized comprehensive diagnostic protocol. In addition, we study the immuno-pathogenesis of severe aplastic anemia with the ultimate aim to guide treatment decisions.

Key Publications

Kaiser FMP, Janowska I, Menafra R, de Gier M, Korzhenevich J, Pico-Knijnenburg I, Khatri I, Schulz A, Kuijpers TW, Lankester AC, Konstantinidis L, Erlacher M, Kloet S, van Schouwenburg PA, Rizzi M, van der Burg M. IL-7 receptor signaling drives human B-cell progenitor differentiation and expansion. Blood. 2023 Sep 28;142(13):1113-1130. 10.1182/blood.2023019721

Takada S, Weitering TJ, van Os NJH, Du L, Pico-Knijnenburg I, Kuipers TB, Mei H, Salzer E, Willemsen MAAP, Weemaes CMR, Pan-Hammarstrom Q, van der Burg M. Causative mechanisms and clinical impact of immunoglobulin deficiencies in ataxia telangiectasia. J Allergy Clin Immunol. 2024 May;153(5):1392-1405. 10.1016/j.jaci.2023.12.029

Ott de Bruin LM, Pico-Knijnenburg I, van Ostaijen-Ten Dam MM, Weitering TJ, Berghuis D, Bredius RGM, Lankester AC, van der Burg M. Persistent Hypogammaglobulinemia after Receiving Rituximab Post-HSCT Is Not Caused by an Intrinsic B Cell Defect. Int J Mol Sci. 2023 Nov 6;24(21):16012. 10.3390/ijms242116012

Vissers L, van der Burg M, Lankester A, Smiers F, Mohseny A. Optimizing diagnostic methods and stem cell transplantation outcomes in pediatric bone marrow failure: a 50-year single center experience. Eur J Pediatr. 2023;182(9):4195-203. 10.1007/s00431-023-05093-y

Tulling AJ, Lugthart G, Mooij MG, Brackel CLH, Terheggen-Lagro SWJ, Oostenbrink R, Buysse CMP, Hashimoto S, Armbrust W, Bannier M, Bekhof J, van Gameren-Oosterom HB, Hendriks H, van Houten MA, van der Linden JW, Lebon A, van Onzenoort-Bokken L, Tramper-Stranders GA, van Veen M, von Asmuth EGJ, Buddingh EP, group CO-s. Severe Pediatric COVID-19 and Multisystem Inflammatory Syndrome in Children From Wild-type to Population Immunity: A Prospective Multicenter Cohort Study With Real-time Reporting. Pediatr Infect Dis J. 2023;42(12):1077-85. 10.1097/INF.0000000000004098

Weitering TJ, Willemsen M, Taylor AMR, Weemaes CMR, van der Burg M, Berghuis D. Early Diagnosis of Ataxia Telangiectasia Through Newborn Screening for SCID: a Case Report Highlighting the Dilemma of Pre-emptive HSCT. J Clin Immunol. 2023;43(8):1770-3. 10.1007/s10875-023-01571-y

Blom M, Zetterström RH, Stray-Pedersen A, Gilmour K, Gennery AR, Puck JM, van der Burg M. Recommendations for uniform definitions used in newborn screening for severe combined immunodeficiency. J Allergy Clin Immunol. 2022 Apr;149(4):1428-1436. 10.1016/j.jaci.2021.08.026

Melsen, J. E., van Ostaijen-Ten Dam, M. M., van den Akker, E. B., Welters, M. J. P., Heezen, K. C., Pico-Knijnenburg, I., Kolijn, P. M., Bredius, R. G. M., van Doorn, R., Langerak, A. W., Schilham, M. W., & Lankester, A. C. (2022). T and NK Cells in IL2RG-Deficient Patient 50 Years After Hematopoietic Stem Cell Transplantation. J Clin Immunol. https://doi.org/10.1007/s10875-022-01279-5 

Atmar, K., Ruivenkamp, C. A. L., Hooimeijer, L., Nibbeling, E. A. R., Eckhardt, C. L., Huisman, E. J., Lankester, A. C., Bartels, M., Santen, G. W. E., Smiers, F. J., van der Burg, M., & Mohseny, A. B. (2022). Diagnostic Value of a Protocolized In-Depth Evaluation of Pediatric Bone Marrow Failure: A Multi-Center Prospective Cohort Study. Front Immunol, 13, 883826. https://doi.org/10.3389/fimmu.2022.883826 

Takada, S., Pico-Knijnenburg, I., Pac, M., Warris, A., & van der Burg, M. (2022). A Pitfall of Whole Exome Sequencing: Variants in the 5'UTR Splice Site of BTK Causing XLA. J Clin Immunol, 42(3), 709-712. https://doi.org/10.1007/s10875-021-01198-x 

Blom, M., Zetterstrom, R. H., Stray-Pedersen, A., Gilmour, K., Gennery, A. R., Puck, J. M., & van der Burg, M. (2022). Recommendations for uniform definitions used in newborn screening for severe combined immunodeficiency. J Allergy Clin Immunol, 149(4), 1428-1436. https://doi.org/10.1016/j.jaci.2021.08.026 

Weitering, T. J., Melsen, J. E., van Ostaijen-Ten Dam, M. M., Weemaes, C. M. R., Schilham, M. W., & van der Burg, M. (2021). Normal Numbers of Stem Cell Memory T Cells Despite Strongly Reduced Naive T Cells Support Intact Memory T Cell Compartment in Ataxia Telangiectasia. Front Immunol, 12, 686333. https://doi.org/10.3389/fimmu.2021.686333 

van der Maas, N. G., von Asmuth, E. G. J., Berghuis, D., van Schouwenburg, P. A., Putter, H., van der Burg, M., & Lankester, A. C. (2021). Modeling Influencing Factors in B-Cell Reconstitution After Hematopoietic Stem Cell Transplantation in Children. Front Immunol, 12, 684147. https://doi.org/10.3389/fimmu.2021.684147 

Blom, M., Bredius, R. G. M., Jansen, M. E., Weijman, G., Kemper, E. A., Vermont, C. L., Hollink, I., Dik, W. A., van Montfrans, J. M., van Gijn, M. E., Henriet, S. S., van Aerde, K. J., Koole, W., Lankester, A. C., Dekkers, E., Schielen, P., de Vries, M. C., Henneman, L., van der Burg, M., & Group, S. O.-S. (2021). Parents' Perspectives and Societal Acceptance of Implementation of Newborn Screening for SCID in the Netherlands. J Clin Immunol, 41(1), 99-108. https://doi.org/10.1007/s10875-020-00886-4 

Our Team members

Associate professor

Mirjam van der Burg, PhD

Assistant professor

Elisabeth Salzer, MD, PhD

Post-doctoral researchers

Gertjan Lugthart, MD, PhD
Maartje Blom, MD, PhD
Lisa Ott de Bruin, MD, PhD
Johannes Bigenzahn, MD, PhD
Janine Melsen, PhD

PhD students

Erik von Asmuth, MD
Adam Tulling, MD
Thomas Weitering, MD, MSc
Melanie de Gier, MSc
Lisa Oostenbrink, MD, MSc
Lotte Vissers, MSc
Annelotte Duintjer, MD
Marco Dijmarescu, MSc

Technicians

Monique van Ostaijen-ten Dam
Ingrid Pico-Knijnenburg
Marloes Holierhoek

Clinician-researchers

Prof. Arjan Lankester, MD, PhD
Robbert Bredius, MD, PhD
Dagmar Berghuis, MD, PhD
Alexander Mohseny, MD, PhD
Emmeline Buddingh, MD, PhD
Anne de Pagter, MD, PhD
Petra Hissink Muller, MD, PhD
Daniëlle Brinkman, MD, PhD