Hanna IJspeert, PhD

Primary Immunodeficiency Disorders (PID) research group


Primary Immunodeficiency Disorders (PID) research group

Primary immunodeficiency disorders (PID) are a heterogeneous group of disorders caused by a defect in the immune system. The clinical manifestations of PID patients are heterogeneous but include increased susceptibility for infections, granulomas, autoimmune disease and increased risk for developing malignancies.

The research aims at improving our understanding of molecular and cellular mechanisms that lead to immune dysregulation in patients with PID. A more specific aim is to use such information to improve diagnostics and to identify new therapeutic targets.

Current studies focus on:

  1. Functional validation of (new) genetic defects
  2. Neutralizing anti-cytokine-autoantibodies (ACA) in PID patients
  3. Pathogenesis of granulomas in PID

The research combines molecular studies with functional analyses. The molecular studies include sequencing of the immune repertoire, for which we developed the analysis tool Antigen Receptor Galaxy (ARGalaxy) https://bioinf-galaxian.erasmusmc.nl/argalaxy.

The research is done in close collaboration with laboratory specialists (Wim Dik and Ton Langerak) from the Laboratory Medical Immunology (LMI) as well as medical specialists from the department of Internal Medicine and Pediatrics.

Selected Publications

(See all publications for Hanna Ijspeert in Pubmed)

IJspeert H, van Schouwenburg PA, Pico-Knijnenburg I, Loeffen J, Brugieres L, Driessen GJ, Blattmann C, Seuring M, Januszkiewicz-Lewandoska D, Azizi AA, Seidel MG, Jacobs H, van der Burg M. Repertoire sequencing of B cells elucidates the role of UNG and mismatch repair proteins in somatic hypermutions in humans. Front Immunol. In press

van Schouwenburg PA*, IJspeert H*, Pico-Knijnenburg I, Dalm VASH, van Hagen PM, van Zessen D, Stubbs AP, Patel SY, van der Burg M. Identification of CVID Patients With Defects in Immune Repertoire Formation or Specification. Front Immunol. doi: 10.3389/fimmu.2018.02545 (2018)

Schoenaker MHD, Henriet SS, Zonderland J, van Deuren M, Pan-Hammerstrom Q, Posthumus-van Sluijs S, Pico-Knijnenburg I, Weemaes CMR, IJspeert H#. Immunodeficiency in Bloom’s syndrome. J Clin Immunol. doi:10.1007/s10875-017-0454-y (2018)

IJspeert 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. doi:10.4049/jimmunol.1601921 (2017)

IJspeert H*, van Schouwenburg PA*, van Zessen D, Pico-Knijnenburg I, Driessen GJ, Stubbs AP, van der Burg M. Evaluation of the antigen-experienced B-cell receptor repertoire in healthy children and adults. Front Immunol. doi: 10.3389/fimmu.2016.00410 (2016)

IJspeert H, Rozmus J, Schwarz K, Warren RL, van Zessen D, Holt RA, Pico-Knijnenburg I, Simons E, Jerchel I, Wawer A, Lorenz M, Patrioglu T, Akar HH, Leite R, Verkaik N, Stubbs AP, van Gent DC, van Dongen JJM, van der Burg M. XLF deficiency results in reduced N-nucleotide addition during V(D)J recombination. Blood. doi: 10.1182/blood-2016-02-701029 (2016)

Driessen GJ*, IJspeert H*, 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 Immun. doi: 10.1016/j.jaci.2016.07.010 (2016)

IJspeert H, Wentink M, van Zessen D, Driessen GJ, Dalm VASH, van Hagen MP, Pico-Knijnenburg I, Simons EJ, van Dongen JJM, Stubbs AP, van der Burg M. Strategies for B-cell receptor repertoire analysis in primary immunodeficiencies: from severe combined immunodeficiency to common variable immunodeficiency. Front. Immunol. doi: 10.3389/fimmu.2015.00157.(2015)

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 JJM, van der Burg M. Similar recombination-activating gene (RAG) mutations result in similar immunobiological effects but in different clinical phenotypes. J Allergy Clin Immunol. doi: 10.1016/j.jaci.2013.11.028 (2014)

IJspeert H, Warris A, van der Flier M, Reisli I, Keles S, Chishimba S, van Dongen JJM, van Gent DC, van der Burg M. Clinical spectrum of LIG4 deficiency is broadened with severe dysmaturity, primordial dwarfism and neurological abnormalities. Hum Mut. doi: 10.1002/humu.22436.(2014)

Driessen GJ*, IJspeert H*, Weemaes CMR, Haraldsson A, Trip M, Warris A, van der Flier M, Wulffraat N, Verhagen MMM, Taylor MA, van Zelm MC, van Dongen JJM, 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. doi: 10.1016/j.jaci.2013.01.053 (2013)

Kuijpers TW, IJspeert H, van Leeuwen EEM, Jansen MH, Hazenberg MD, Weijer KC, van Lier RAW, van der Burg M. Idiopathic CD4+ T lymphopenia without autoimmunity or granulomatous disease in the slipstream of RAG mutations. Blood. doi: 10.1182/blood-2011-01-329052.

IJspeert H, Lankester AC, van den Berg JM, Wiegant W, van Zelm MC, Weemaes CMR,  Warris A, Pan-Hammarström Q, Pastink A,  van Tol MJD, van Dongen JJM, van Gent DC, van der Burg M. Artemis splice defects cause atypical SCID and can be restored in vitro by an antisense oligonucleotide. Genes and Immunity, doi: 10.1038/gene.2011.16. (2011)

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 JJM, van Gent DC. A DNA-PKcs mutation in a radio­sensitive T-B- SCID patient inhibits Artemis activation and nonhomologous end-joining.

J Clin Invest, doi: 10.1172/JCI37141.(2009)