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

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 

Ijspeert, H., van Schouwenburg, P.A., Pico-Knijnenburg, I., Loeffen, J., Brugieres, L., Driessen, G.J., Blattmann, C., Suerink, M., Januszkiewicz-Lewandowska, D., Azizi, A.A., Seidel, M.G., Jacobs, H., van der Burg, M. (2019) Repertoire Sequencing of B Cells Elucidates the Role of UNG and Mismatch Repair Proteins in Somatic Hypermutation in Humans. Front Immunol. 2019 Aug 27;10:1913.
https://doi.org/10.3389/fimmu.2019.01913

Oostenbrink, L. V. E., Jol-van der Zijde, C. M., Kielsen, K., Jansen-Hoogendijk, A. M., Ifversen, M., Muller, K. G., Lankester, A. C., van Halteren, A. G. S., Bredius, R. G. M., Schilham, M. W., & van Tol, M. J. D. (2019). Differential Elimination of Anti-Thymocyte Globulin of Fresenius and Genzyme Impacts T-Cell Reconstitution After Hematopoietic Stem Cell Transplantation. Front Immunol, 10, 315. https://doi.org/10.3389/fimmu.2019.00315 

Melsen, J. E., Lugthart, G., Vervat, C., Kielbasa, S. M., van der Zeeuw, S. A. J., Buermans, H. P. J., van Ostaijen-Ten Dam, M. M., Lankester, A. C., & Schilham, M. W. (2018). Human Bone Marrow-Resident Natural Killer Cells Have a Unique Transcriptional Profile and Resemble Resident Memory CD8(+) T Cells. Front Immunol, 9, 1829. https://doi.org/10.3389/fimmu.2018.01829 

Haasnoot, A. J. W., Schilham, M. W., Kamphuis, S., Hissink Muller, P. C. E., Heiligenhaus, A., Foell, D., Minden, K., Ophoff, R. A., Radstake, T., Den Hollander, A. I., Reinards, T., Hiddingh, S., Schalij-Delfos, N. E., Hoppenreijs, E., van Rossum, M. A. J., Wouters, C., Saurenmann, R. K., van den Berg, J. M., Wulffraat, N. M., Group, I.-J. S., Ten Cate, R., de Boer, J. H., Pulit, S. L., & Kuiper, J. J. W. (2018). Identification of an Amino Acid Motif in HLA-DRbeta1 That Distinguishes Uveitis in Patients With Juvenile Idiopathic Arthritis. Arthritis Rheumatol, 70(7), 1155-1165. https://doi.org/10.1002/art.40484 

Lugthart, G., Goedhart, M., van Leeuwen, M. M., Melsen, J. E., Jol-van der Zijde, C. M., Vervat, C., van Ostaijen-Ten Dam, M. M., Jansen-Hoogendijk, A. M., van Tol, M. J. D., Lankester, A. C., & Schilham, M. W. (2017). Expansion of cytotoxic CD56(bright) natural killer cells during T-cell deficiency after allogeneic hematopoietic stem cell transplantation. J Allergy Clin Immunol, 140(5), 1466-1469. https://doi.org/10.1016/j.jaci.2017.06.039 

Melsen, J. E., Lugthart, G., Lankester, A. C., & Schilham, M. W. (2016). Human Circulating and Tissue-Resident CD56(bright) Natural Killer Cell Populations. Front Immunol, 7, 262. https://doi.org/10.3389/fimmu.2016.00262 

Our Team members

Associate professors

Dr. Marco Schilham, head of laboratory
Dr. Mirjam van der Burg

Post-doctoral researchers

Dr. Elisabeth Salzer
Dr. Gertjan Lugthart
Dr. Michiel Schoenaker
Dr. Maartje Blom
Dr. Lisa Ott de Bruin

PhD students

Janine Melsen
Erik von Asmuth
Joel Bense
Adam Tulling
Thomas Weitering
Melanie de Gier
Lisa Oostenbrink
Anne Verbeek

Technicians

Monique van Ostaijen-ten Dam
Anja Jansen-Hoogendijk
Ingrid Pico
Aafke de Ligt

Clinician-researchers

Prof. Dr. Arjan Lankester
Dr. Frans Smiers
Dr. Robbert Bredius
Dr. Dagmar Berghuis
Dr. Alexander Mohseny
Dr. Emmeline Buddingh
Dr. Anne de Pagter
Dr. Petra Hissink Muller
Dr. Daniëlle Brinkman