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Mirjam van der Burg, PhD

Burg,-van-der51x53px Associate Professor, Laboratory Medical Immunology,
 Department of Immunology

 Email contact:
 For PID diagnostics:
                                     tel: +31-10-7043015/4094

 Primary Immunodeficiency (PID) Research Group

The two main research lines of the Workgroup Primary Immunodeficiencies are:

  1. DNA repair in the immune system, especially V(D)J recombination and its defects  in severe combined immunodeficiency and DNA repair disorders.
  2. Immunopathological causes and consequences of primary antibody deficiencies.

The main research interest of PID research group is the generation of a diverse immune receptor repertoire. The generation of this repertoire is based on several molecular mechanisms that are mediated via DNA repair in the context of B- and T-cell  differentiation in bone marrow, thymus and peripheral lymphoid organs. During the past five years, we developed a strategy to measure and visualize the immune repertoire via next generation sequencing and a bioinformatic pipeline based on my Vidi grant “Immune repertoire in the picture”. We used material from patients with monogenetic defects in repertoire formation, DNA repair and B- and T-cell differentiation (i.e. patients with primary immunodeficiencies (PID). These patients are rare, but because of our strong national and international position in the PID field, patient samples were relatively easy accessible. The results of our study gave new insights into fundamental aspects of immune repertoire development on one hand and in the immunopathological causes of the studied PID on the other hand. The strength of our approach is the combination of fundamental immunological research, advanced technologies and our diagnostic position in the  PID field, especially on severe combined immunodeficiency (SCID), DNA repair disorders and antibody deficiencies. As spin of our repertoire studies, we initiated several new national and international collaborations. 

Reference center for PID diagnostics
The Workgroup PID is a national and international reference center for flowcytometric and molecular diagnostics for PID of the adaptive immune system  such as antibody deficiencies and T-cell disorders including severe combined immunodeficiencies.

 Group members

Mirjam van der Burg, Group leader
Hanna IJspeert, PhD
Pauline van Schouwenburg, PhD
Marjolein Wentink, MD, PhD student
Fabian Kaiser, MD, PhD student
Barbara Barendregt, Research Assistant
Ingrid Pico, Research Assistant
Sandra Posthumus, Research Assistant
Hanna Kok, Research Assistant
David van Zessen, bioinformatician




 Selected Publications

(See for all publications: van der Burg M in Pubmed)

Wentink M, Dalm V, Lankester AC, van Schouwenburg PA, Scholvinck L, Kalina T, Zachova R, Sediva A, Lambeck A, Pico-Knijnenburg I, van Dongen JJ, Pac M, Bernatowska E, van Hagen M, Driessen G, van der Burg M.
Genetic defects in PI3Kdelta affect B-cell differentiation and maturation leading to hypogammaglobulineamia and recurrent infections.
Clin Immunol. 2017;176:77-86.

IJpeert H, van Schouwenburg PA, van Zessen D, Pico-Knijnenburg I, Stubbs AP, van der Burg M.
Antigen Receptor Galaxy: A User-Friendly, Web-Based Tool for Analysis and Visualization of T and B Cell Receptor Repertoire Data.
J Immunol 2017; 198:4156-65.

IJspeert H, Rozmus J, Schwarz K, Warren RL, van Zessen D, Holt RA, Pico-Knijnenburg I, Simons E, Jerchel I, Wawer A, Lorenz M, Patiroglu T, Akar HH, Leite R, Verkaik NS, Stubbs AP, van Gent DC, van Dongen JJ, van der Burg M.
XLF deficiency results in reduced N-nucleotide addition during V(D)J recombination.
Blood. 2016;128:650-659.

Driessen GJ, H IJ, Wentink M, Yntema HG, van Hagen PM, van Strien A, Bucciol G, Cogulu O, Trip M, Nillesen W, Peeters EA, Pico-Knijnenburg I, Barendregt BH, Rizzi M, van Dongen JJ, Kutukculer N, van der Burg M.
Increased PI3K/Akt activity and deregulated humoral immune response in human PTEN deficiency.
J Allergy Clin Immunol. 2016;138:1744-1747 e1745.

Murray JE,# van der Burg M,# IJspeert H, Carroll P, Wu Q, Ochi T, Leitch A, Miller ES, Kysela B, Jawad A, Bottani A, Brancati F, Cappa M, Cormier-Daire V, Deshpande C, Faqeih EA, Graham GE, Ranza E, Blundell TL, Jackson AP, Stewart GS, Bicknell LS.
Mutations in the NHEJ component XRCC4 cause primordial dwarfism.
Am J Hum Genet. 2015;96:412-424.

IJspeert H, Driessen GJ, Moorhouse MJ, Hartwig NG, Wolska-Kusnierz B, Kalwak K, Pituch-Noworolska A, Kondratenko I, van Montfrans JM, Mejstrikova E, Lankester AC, Langerak AW, van Gent DC, Stubbs AP, van Dongen JJ, van der Burg M.
Similar recombination-activating gene (RAG) mutations result in similar immunobiological effects but in different clinical phenotypes.
J Allergy Clin Immunol. 2014;133:1124-1133 e1121.

Genovese P, Schiroli G, Escobar G, Di Tomaso T, Firrito C, Calabria A, Moi D, Mazzieri R, Bonini C, Holmes MC, Gregory PD, van der Burg M, Gentner B, Montini E, Lombardo A, Naldini L.
Targeted genome editing in human repopulating haematopoietic stem cells.
Nature. 2014;510:235-240.

Driessen GJ, Ijspeert H, Weemaes CM, Haraldsson A, Trip M, Warris A, van der Flier M, Wulffraat N, Verhagen MM, Taylor MA, van Zelm MC, van Dongen JJ, van Deuren M, van der Burg M.
Antibody deficiency in patients with ataxia telangiectasia is caused by disturbed B- and T-cell homeostasis and reduced immune repertoire diversity.
J Allergy Clin Immunol. 2013;131:1367-1375 e1369.

Driessen GJ, van Zelm MC, van Hagen PM, Hartwig NG, Trip M, Warris A, de Vries E, Barendregt BH, Pico I, Hop W, van Dongen JJ, van der Burg M.
B-cell replication history and somatic hypermutation status identify distinct pathophysiologic backgrounds in common variable immunodeficiency.
Blood. 2011;118:6814-6823.

van Zelm MC, Smet J, Adams B, Mascart F, Schandene L, Janssen F, Ferster A, Kuo CC, Levy S, van Dongen JJ, van der Burg M.
CD81 gene defect in humans disrupts CD19 complex formation and leads to antibody deficiency.
J Clin Invest. 2010;120:1265-1274.

van der Burg M, Ijspeert H, Verkaik NS, Turul T, Wiegant WW, Morotomi-Yano K, Mari PO, Tezcan I, Chen DJ, Zdzienicka MZ, van Dongen JJ, van Gent DC.
A DNA-PKcs mutation in a radiosensitive T-B- SCID patient inhibits Artemis activation and nonhomologous end-joining.
J Clin Invest. 2009;119:91-98.

van Zelm MC, Reisli I, Van der Burg M, Castano D, van Noesel CJ, van Tol MJ, Woellner C, Grimbacher B, Patino PJ, van Dongen JJM, Franco JL.
An antibody-deficiency syndrome due to mutations in the CD19 gene.
N Engl J Med. 2006;354:1901-1912.