Academic Center for Rare Immunological Disease

  1. To optimize early diagnosis, improve patient care and implement novel treatment strategies for patients with auto-immune, auto-inflammatory and immunodeficiency diseases (immunodysregulation disorders).
  2. To improve personalized medicine by identifying a) disease-causing genetic defects and b) defective pathways resulting in specific disease (manifestations) in patients, leading to a "from bedside to bench and back to bedside approach".
Academic Center of Excellence

Research Activities

The AC for Rare Immunological Disease (RIDC) holds strong collaborations between the participating laboratories and clinical departments to ensure fundamental, translational and clinical research projects. Members of the various disciplines are involved in the AC's research projects. Results of fundamental research can be implemented in clinical care and in clinical studies.

The biotechnology of our laboratory partners is used to evaluate effects of novel treatment strategies.

Research activities in rare primary immunodeficiency diseases, autoinflammatory disorders and systemic autoimmune diseases (amongst others Morbus Sjögren, Behçet’s disease, systemic sclerosis, systemic lupus erythematodes, uveitis, vasculitis, IgG4-related disease and hemofagocytic lymfohistiocytosis (HLH) ) include the following projects:

Primary imunodeficiency disease (PID):

The role of V(D)J recombination in common variable immunodeficiency disorder (CVID) development (fundamental) (ZonMW Veni, 2015-2018)

Genetics first in primary imunodeficiency disease (clinical) (ZonMw Doelmatigheid, 2016-2020)

Genes and Immunity in SCID (translational)

Mood disorders in primary immunodeficiencies (translational/clinical) (Horizon 2020 Moodstratification, 2018-2022)

Clinical trial in Activated PI3K delta syndrome (APDS) with leniolisib (supported by Novartis, 2016-2020)

Endocrine dysfunction in primary immunodeficiencies (translational/clinical) (non-restricted educational grant by Novartis, 2016-2020)

Skin disorders in primary immunodeficiencies (translational/clinical) (non-restricted educational grant by Micreos HUman Health B.V., 2017-2020)

The different roads to immune deficiency; genetic and inflammatory syndromes (non-restriced educational grant by Baxalta/Shire 2016-2019)

Autoinflammatory disorders

Personalized Risk assessment in febrile illness to Optimize Real-life Management across the European Union (PERFORM, Horizon 2020) fundamental, translational and clinical;2015-2020)

Immunome project consortium for AutoInflammatory Disorders (ImmunAID; Horizon 2020, 2018-2012)

Behçet’s disease(BD)


The role of the microbiome in BD

WES in BD like diseases


Systemic sclerosis

Clinical trials focussing on pulmonary involvement (in colaboration with Boehringer Ingelheim) and cutaneous involvement (in colaboration with Corbus and Inventiva)

Determination of biomarkers in systemic sclerosis (non-restricted educational grant by Actelion BV, 2015-2020)

Morbus Sjogren and systemic lupus erythematodes

Clinical trials

Transaltional research project on interferon signature in Morbus Sjogren (Reumafonds project, 2017-2021)


Biobanking of patients with uveitis


Clinical trials in Granulomatosis with Polyangiitis (GPA)

IgG4 related disease(IgG4RD)

Bio -and databanking.

Clincical trial with liposomal steroïd (nanocort)


T-cell and NK cell analysis in HLH patients (Ter Meulen grant)

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Various international collaborations with top institutes exist to explore and improve international research collaborations and optimize standard of care for patients with rare immunological diseases. The AC for Rare Immunological Disease includes NFU recognized Centers of Expertise for Primary Immunodeficiencies and Rare Immune Diseases.

The "Academic Center for Rare Immunolgical Disease" (RIDC) is core member of 2 European Reference Networks, established by the European Union. The ERNs the AC is involved in include RITA (immunodeficiency, autoinflammatory and autoimmune diseases) and ReCONNET (connective tissue and musculoskeletal disease), respectively. Within these ERNs, current active projects include the establishment of European guidelines for disease specific patient care, such as for systemic sclerosis, and the initiation of collaborative, European research projects.

Stronger collaboration with LUMC in relation to primary immunodeficiencies (in DELTA-PID) has been established and the collaboration with the division of bioinformatics, department of pathology and Department of Genetics of Erasmus MC has resulted in identification of novel disease-causing genetic defects resulting in new therapeutic approaches.

The AC had a leading role in establishment of the South-East-Asian PID network, set-up to improve diagnostics and patient care in this region of the world.

Novel research projects in the ACE focus on immunological, autoinflammatory and immunodeficiency diseases. project ImmunoAid , recently approved in 2017 and Horizon 2020 "Mood stratification" and non-immunological complications of immune-mediated diseases. As an example, a recently approved Horizon 2020 project focusses on the psychiatric complications of primary immunodeficiencies (PID), resulting in a new collaboration with the department of psychiatry. A clinical novo collaboration is patient care in the Eye Hospital Rotterdam, which will be connected directly to research. Collaboration with LUMC paediatrics and dept. of Infectious Disease resulted in Deltacare for immunodeficiencies (DELTAPID). Future new initiatives will further strengthen consisting and establish new collaborations with other departments/specialties, not classically involved in care and research in immune-mediated diseases.

We developed with the South/East Asian primary immunodeficiency network in cooperation with Uitterlinden Laboratory and Bioinformatics/Pathology a new cheap diagnostic method for genetic diagnosis of PID. This will be presented at the European Society of Immunodeficiencies in October 2018.

Department of Pathology and Bioinformatics: Artificial Intelligence is currently mainly used in search engines of Google and Facebook to optimize advertisements. We have used these techniques in a Hackaton to study the variation in the genome of RID patients. Deciphering the secrets of our DNA is working very well with these Big Data based methods and technology. In June 2018 we organized together with the Dutch ABN AMRO bank a Hackaton where bank ICT expertise was combined with data of Erasmus MC clinicians studying the contributions of the genome to health and disease.

Department of Dermatology: For patients (adolescents) we have set up joint outpatient clinics for primary immunodeficiencies, including Netherton syndrome

Department of Pulmonary disease: We have initiated collaborative research projects on systemic sclerosis, including a clinical trial, a prospective cohort study

ACE Respiratory infections: In the past year we have improved multidisciplinary care for patients with primary immunodeficiencies (joint out-patient clinics) and to further emphasize the importance of joint care we have organized symposia in close collaboration

HLH in adult patients; Cellular and molecular functional analyses in collaboration with prof Brycesons lab at the Karolinska University, Sweden. An AIO will be stationed for at least 6 months in Karolinska and promote joined pateints sampling and evaluation.

Behçet's disease; WES and microbiomes. Collaboration with specialized Behçet centers in the universities of Birmingham, Florence and Istanbul. Joined sampling and analysis.

Behçet's disease like syndromes (eq HA20 insufficiency and other rare molecular abberations): WES studies with National Human Research Genome Institute, Bethesda, USA, and Istanbul Faculty of Medicine of Istanbul University

IgG4RD: Eye hospital; inflammatory orbital disease with IgG4RD; joined PhD project. Clincial collaboration with END, pulmonology and ophthalmology departments EMC.



This AC is actively involved in the education of bachelor and master students in medicine (especially 2nd and 3rd year) and in the Master Programs Infection & Immunity, Clinical Technology and Molecular Medicine.

Members of the AC participate in training of interns and residents (Internal Medicine, Ophthalmology, Dermatology, Pulmonology, Rheumatology, Pediatrics, ENT, Neurology, fellows in Allergy/Clinical Immunology) and are responsible for training in Allergy and Clinical Immunology.

Members of the AC organize and participate in regional, national and international conferences for medical specialists to broaden the knowledge in rare immunological diseases.

Novel e-learning educational programs, i.e. minors, are developed and under development for medical students, nurses and interns/residents.

The AC facilitates international exchange programs (Bangkok (Thailand), Jakarta (Indonesia) and Paramaribo (Surinam) and tends to host 2-4 international students yearly.


Care Activities

Clinical care for the patients in the AC is >80% labelled as academic and defined in multidisciplinary care-pathways. All healthcare professionals in this care-path are responsible for care of the patient and one healthcare professional is the designated coordinator of care in this care-path. Once weekly or bi-weekly multidisciplinary meetings are scheduled to discuss patient cases and best practices.

Multidisciplinary outpatient clinics are established in order to improve efficacy of care and patients' satisfaction (for example between the departments of internal medicine and respiratory medicine)

The AC focusses on so-called "from bedside to bench and back to bedside" care. When a patient is seen at the outpatient clinics with a rare disease, genetic or pathway analysis is performed at the lab. Furthermore, potential new drugs are evaluated in vitro for very rare conditions in order to implement these drugs in clinical practice, thereby providing an example of personalized medicine.

Societal Relevance to Research, Education and Patient Care

The AC aims to broaden the knowledge on rare immunologic diseases among care professionals as well as the general public. Members participate in (inter)national clinical, diagnostic and therapeutic guideline development. Patient education material is developed in collaboration with (inter)national patient organizations. Video materials have been developed that are available via our website and disease specific patient information folders are available in various languages (Dutch, English, Turkish and Moroccan, based on the patient backgrounds that are under treatment at the Erasmus MC) via website and hardcopy. Interactive educational material has been developed (in collaboration with external parties) for healthcare professionals. The AC is involved in development and improvements of the curriculum for medical students and interns.

Focus is on raising awareness for immunological diseases and providing more insights in normal immune cell function and processes that lead to immunological diseases. By strong international collaborations we have implemented newborn screening for immunodeficiencies in the Netherlands. This results in early diagnosis, and subsequent treatment, resulting in prevention of severe disease manifestations, organ damage and premature death. By determining genetic defects, novel gene-targeted therapies are under current clinical exploration and/or development.

Furthermore members of the AC are involved in numerous clinical trials and investigator initiated research projects. The results of the studies are published in peer-reviewed international high-impact journals and are presented to patients and patient organizations on annual or bi-annual meetings organized by the AC for patients and patient organizations. Based on these meetings and patients' preferences novel research questions are addressed.

The AC RIDC organized in September 2018 the global conference and patience conference on Behcet's disease in Rotterdam.

The AC RIDC was involved in presentations at the EU Parlement in 2016/2017 concerning the treatment of patients with PID.

The AC RIDC organized patients meetings with patient foundations in 2016/2017/2018. The subjects include PID, SLE, Vasculitis, Mastocytosis and Behcet's disease.

The AC RIDC advises Zorginstituut concerning the use of immune-mediated inflammatory drugs.

Viability of Research, Education and Patient Care

The Academic Center strives for and succeeds in developing high standards of conduct in a field of research, innovation and education. Our center acquires and develops knowledge by conducting basic and translational research, identifying new therapies, study and compare models of care. We concentrate the resources needed for highly specialized care and serve as an anchor institution for others. We share knowledge with clinical Immunologists and other specialists on (inter)national fora, such as conferences and meetings. More than 500 papers have been published in peer reviewed high ranked papers in the last 5 years. Our collaborations resulted in a continuous flow of successful PhD graduates.

The success of many PhD students can be seen upon their presence at international conferences, where they are invited speaker and/or giving poster presentations. The continuity of the AC is secured by identifying and recruiting talents during short-term clinical rotations, medical education sessions or short-term bioinformatics/genetics and laboratory trainings. Potential talents are offered a short-term research project in order to determine their eligibility to become a PhD student. The progress of all PhD students is annually evaluated by a PhD-board.

Key and relevant publications of the last five years

  • Karim F et al., N Engl J Med. 2017;376:599-600
  • IJspeert et al. Blood. 2016 Jun 8. pii: blood-2016-02-701029
  • Sharma et al. Nat Genet. 2013 Oct;45(10):1261
  • Driessen, IJspeert et al. J Allergy Clin Immunol. 2013 May;131(5):1367-75
  • Kuiper et al. Hum Mol Genet. 2014 Nov 15;23(22):6081-7.
  • La Distia Nora et al. Am J Ophthalmol. 2014 Apr;157(4)
  • Maria et al. Ann Rheum Dis. 2014 jun;73(6)
  • Virakul et al. Invest Ophthalmol Vis Sci. 2015 Aug;56(9):5457-64.
  • Meesilpavikkai K et al. J Allergy Clin Immunol 2018 142(1):328-33
  • Rao VK et al. Blood 2017 Nov 23;130(21):2307-2316

PhD theses of the last five years

  • 2016 S. Virakul: New insights in the Pathogenesis of Graves’Ophthalmology: potentials for targeted therapy
  • 2016 L. Kamphuis: The many faces of Sarcoidosis: Novel insights into pathogenesis, 2016 L.,diagnositics and therapy
  • 2014 H. IJspeert: Clinical and Immunological Diversity of Recombination defects
  • 2014 J. Kuiper: Pathogenesis of birdshot chorioretinopathy
  • 2014 M. Haverkamp: Primary immunodeficiencies, mycobacterial infections, and cytokines
  • 2015 J. Kappen: Translational Aspects of Behçet’s Disease
  • 2013 G. Driessen: Immunobiology of primary antibody deficiencies: towards a new classification
  • 2013 Z. Brkic: Interferon Type 1 Driven Immune Activation in Generalized autoimmune Diseases
  • 2018 R. La Distia Nora: Mycobacterium Tuberculosis-Associated Uveitis: Infection and Autoimmunity
  • 2018 J.C.E.M. ten Berge: Autoimmunity in Uveitis and Other Chorioretinal Diseases
  • 2017 T. Both: Beyond the dryness of Sjogren’s disease
  • 2016 J. Bastiaans A novel role for coagulation proteins in the development of proliferative vitreoretinopathy
  • 2015 N. Maria The Toll of too much Interferon: The systemic interferon signature in the pathogenesis of Sjögren’s syndrome
  • 2018 WMC Timmermans: Immunopathogenesis of granulomas in chronoc inflammatory diseases
  • 2018 J ten Berge Autoimmunity in uveitis and other chorioretinal diseases EMC
  • 2015 A Osserwaarde-Norel: Cystoid macular edema in uveitis UMCU
  • 2014 A Riemens: Eye involvement in haematological malignancies UMCU
  • 2018 M Wentink: Immune repertoire in the picture EMC

Non-scientific publications related to the ACE

  • 2018 Paul van Daele interview Algemeen Dagblad
  • Leaflets International Patients Organisation of Primary Immunodeficiencies
  • 2018 Paul van Daele, interview "Een Vandaag"
  • 2018 Faiz Karim, interview Hart van Zuidplas
  • 2018 Interview P. van der Spek & P.M. van Hagen, ICT/Magazine
  • 2015-2018; 5 tal publicaties Vascuzine (website en 3 jaarlijks magazine vasaculitis stichting)

Principal coordinator(s)

Last updated: 365 days ago.