CClinicalTrials.gg
RecruitingNCT02735824GSIUpdated May 14, 2026

Genetic Study of Immunodeficiency: Search for New Genetic Causes for Primary Immunodeficiencies

An observational study in Immunologic Deficiency Syndromes and Primary Immune Deficiency (PID), sponsored by University Children's Hospital, Zurich. Recruiting at 1 site in Switzerland. Per ClinicalTrials.gov, last updated 2026-05-14.

Sponsored by University Children's Hospital, Zurich · Observational

Study type
Observational
Model
Case-only
Time perspective
Prospective
Enrollment
500
Sex
All
01

Study summary

Individuals with suspected primary immunodeficiency will be studied and the results compared with healthy controls. Primary immunodeficiency may manifest as recurrent, severe or unusual infections as well as signs and symptoms of immune dysregulation such as autoimmunity or lymphoproliferation.

Read the detailed description

Patients with a suspected immunodeficiency will be identified and invited to participate. Upon agreement, an additional blood sample will be collected when they have their routine bloods taken. If the study participants undergoes anaesthesia for any other reason, a small skin biopsy will be taken as well. Additional samples including blood samples or mouth swabs will be taken from healthy family members. Blood from healthy controls will only be taken when there is a clinical need for blood sampling (or when the study participant is already anaesthetised for any other reason) and not for research purposes only.

02

Conditions studied

  • Immunologic Deficiency Syndromes
  • Primary Immune Deficiency (PID)
03

Who can participate

Ages eligible
Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible
All
Accepts healthy volunteers
Yes
Sampling method
Non-probability sample

Study population

The study population consists of pediatric patients (inpatients and outpatients) and individuals referred for immunological evaluation at the University Children's Hospital Zurich from national and international centers. To facilitate comparative analysis, the population also includes healthy biological relatives of these patients and healthy volunteers recruited from the Zurich area and across Switzerland.

Eligibility criteria

Inclusion Criteria:

  • Patients: Pediatric patients (in/outpatient or referred) with suspected or confirmed Inborn Errors of Immunity.
  • Relatives: Healthy or affected biological relatives of enrolled patients.
  • Controls: Healthy volunteers with no history of chronic immunological, inflammatory, or infectious disease.
  • Consent: Ability to provide signed informed consent (or guardian consent).
04

Study design

Observational model
Case-only
Time perspective
Prospective
Enrollment
500 participants (estimated)
Patient registry
No
Biospecimen retention
Samples with dna

Groups and cohorts

  • Patients with suspected PID

    From included patients with suspected primary immunodeficiency (PID), i.e. patients with recurrent/unusual infection, immune dysregulation and/or susceptibility to malignancies from whom consent to participate was obtained, nucleated blood cells and/or fibroblasts from skin biopsy will be used for genetic testing and functional assays. Blood serum will be used for antibody and cytokine measurement.

    Procedure: Skin Biopsy · Procedure: Mouth Swab or Saliva Collection · Procedure: Blood Sampling

  • Healthy Relatives of Patients with PID

    From healthy relatives of patients with suspected PID from whom consent to participate was obtained, nucleated cells will be used for genetic testing in order to compare their genetic information with the one form their relatives with suspected PID.

    Procedure: Mouth Swab or Saliva Collection · Procedure: Blood Sampling

  • Healthy Volunteers

    From healthy volunteers from whom consent to participate was obtained, nucleated blood cells will be used for genetic testing and functional assays. Blood serum will be used for antibody and cytokine measurement. The data obtained will be compared to age matched patients with suspected PID.

    Procedure: Mouth Swab or Saliva Collection · Procedure: Blood Sampling

Interventions

  • ProcedureSkin Biopsy

    A punch biopsy of the skin and underlying connective tissue is performed to establish fibroblast cultures. For pediatric patients, the procedure is conducted while the patient is under general anesthesia for other clinical indications. For adult patients, the biopsy is performed under local anesthesia as needed. This intervention follows cosmetic/aesthetic considerations and is therefore typically collected from the inner aspect of the upper arm.

  • ProcedureMouth Swab or Saliva Collection

    Non-invasive collection of epithelial cells via a swab of the buccal mucosa (inner cheek) to obtain biological material for comparative genetic analysis with minimal burden.

  • ProcedureBlood Sampling

    Collection of nucleated blood cells, serum, and plasma from blood and subsequent genetic testing, functional assays, as well as antibody and cytokine measurements. To minimize risk and burden, blood sampling in pediatric patients is opportunistic (performed during routine clinical diagnostics or while under anesthesia) and capped at 1% of total blood volume per sampling and 3% over a 4-week period (adjusted by body weight). In adult patients, up to 50mL venous blood is sampled, typically performed during clinic visits or routine check-ups.

05

What researchers measure

Primary outcomes

  1. Number of patients with suspected PID for whom a genetic cause has been identified

    Number of patients with suspected primary immunodeficiency included in the study for whom a diagnosis can be made with the genetic and functional data obtained from patients, their relatives and healthy volunteers.

    Time frame: Through study completion, an average of 3 years

06

Study locations

1 of 1 sites recruiting
  • Division of Immunology
    Zurich, Canton of Zurich 8008, Switzerland
    Recruiting
07

References and documents

Publications

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  • Lewandowska DW, Capaul R, Prader S, Zagordi O, Geissberger FD, Kugler M, Knorr M, Berger C, Gungor T, Reichenbach J, Shah C, Boni J, Zbinden A, Trkola A, Pachlopnik Schmid J, Huber M. Persistent mammalian orthoreovirus, coxsackievirus and adenovirus co-infection in a child with a primary immunodeficiency detected by metagenomic sequencing: a case report. BMC Infect Dis. 2018 Jan 11;18(1):33. doi: 10.1186/s12879-018-2946-7. PubMed 29325543 ↗
  • Simonis A, Fux M, Nair G, Mueller NJ, Haralambieva E, Pabst T, Pachlopnik Schmid J, Schmidt A, Schanz U, Manz MG, Muller AMS. Allogeneic hematopoietic cell transplantation in patients with GATA2 deficiency-a case report and comprehensive review of the literature. Ann Hematol. 2018 Oct;97(10):1961-1973. doi: 10.1007/s00277-018-3388-4. Epub 2018 Jun 13. PubMed 29947977 ↗
  • Mauracher AA, Gujer E, Bachmann LM, Gusewell S, Pachlopnik Schmid J. Patterns of Immune Dysregulation in Primary Immunodeficiencies: A Systematic Review. J Allergy Clin Immunol Pract. 2021 Feb;9(2):792-802.e10. doi: 10.1016/j.jaip.2020.10.057. Epub 2020 Nov 11. PubMed 33186766 ↗
  • Truck J, Prader S, Natalucci G, Hagmann C, Brotschi B, Kelly J, Bassler D, Steindl K, Rauch A, Baumgartner M, Fingerhut R, Hauri-Hohl M, Gungor T, Pachlopnik Schmid J, Berger C, Reichenbach J. Swiss newborn screening for severe T and B cell deficiency with a combined TREC/KREC assay - management recommendations. Swiss Med Wkly. 2020 Jun 24;150:w20254. doi: 10.4414/smw.2020.20254. eCollection 2020 Jun 15. PubMed 32579701 ↗
  • Mauracher AA, Pagliarulo F, Faes L, Vavassori S, Gungor T, Bachmann LM, Pachlopnik Schmid J. Causes of low neonatal T-cell receptor excision circles: A systematic review. J Allergy Clin Immunol Pract. 2017 Sep-Oct;5(5):1457-1460.e22. doi: 10.1016/j.jaip.2017.02.009. Epub 2017 Mar 27. No abstract available. PubMed 28359806 ↗
  • Lemoine R, Pachlopnik-Schmid J, Farin HF, Bigorgne A, Debre M, Sepulveda F, Heritier S, Lemale J, Talbotec C, Rieux-Laucat F, Ruemmele F, Morali A, Cathebras P, Nitschke P, Bole-Feysot C, Blanche S, Brousse N, Picard C, Clevers H, Fischer A, de Saint Basile G. Immune deficiency-related enteropathy-lymphocytopenia-alopecia syndrome results from tetratricopeptide repeat domain 7A deficiency. J Allergy Clin Immunol. 2014 Dec;134(6):1354-1364.e6. doi: 10.1016/j.jaci.2014.07.019. Epub 2014 Aug 28. PubMed 25174867 ↗
  • Pachlopnik Schmid J, Gungor T, Seger R. Modern management of primary T-cell immunodeficiencies. Pediatr Allergy Immunol. 2014 Jun;25(4):300-13. doi: 10.1111/pai.12179. Epub 2014 Jan 3. PubMed 24383740 ↗
  • Planas R, Felber M, Vavassori S, Pachlopnik Schmid J. The hyperinflammatory spectrum: from defects in cytotoxicity to cytokine control. Front Immunol. 2023 Apr 28;14:1163316. doi: 10.3389/fimmu.2023.1163316. eCollection 2023. PubMed 37187762 ↗
  • Prader S, Ritz N, Baleydier F, Andre MC, Stahli N, Schmid K, Schmid H, Woerner A, Diesch T, Meyer Sauteur PM, Truck J, Gebistorf F, Opitz L, Killian MP, Marchetti T, Vavassori S, Blanchard-Rohner G, Mc Lin V, Grazioli S, Pachlopnik Schmid J. X-Linked Lymphoproliferative Disease Mimicking Multisystem Inflammatory Syndrome in Children-A Case Report. Front Pediatr. 2021 Aug 3;9:691024. doi: 10.3389/fped.2021.691024. eCollection 2021. PubMed 34414143 ↗
  • Lorenzini T, Malmstrom L, Sabet O, Milanesi S, Tintor D, Walser S, Koppen J, Soomann M, Hauri-Hohl M, Prader S, Doffinger R, Pachlopnik Schmid J. Case report: anti-IL-6 autoantibodies in a patient with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome. Front Immunol. 2025 Sep 4;16:1660161. doi: 10.3389/fimmu.2025.1660161. eCollection 2025. PubMed 40977713 ↗
  • Milanesi S, Lorenzini T, Marchetti T, Tintor D, Planas R, Sabet O, Malmstrom L, Acharya S, Williams CD, Manning ZE, Roser JH, Ehler AC, Huber M, Prader S, Vavassori S, Dutmer CM, Abbott JK, Pachlopnik Schmid J. Variants in human CD48 lead to impaired T cell immunity and increased inflammation. J Clin Invest. 2026 Apr 14;136(11):e191340. doi: 10.1172/JCI191340. eCollection 2026 Jun 1. PubMed 41984595 ↗
  • Marquardt L, Lacour M, Hoernes M, Opitz L, Lecca R, Volkmer B, Reichenbach J, Hohl D, Ansari M, Ozsahin H, Gungor T, Pachlopnik Schmid J. Unusual dermatological presentation and immune phenotype in SCID due to an IL7R mutation: the value of whole-exome sequencing and the potential benefit of newborn screening. J Eur Acad Dermatol Venereol. 2017 Mar;31(3):e147-e148. doi: 10.1111/jdv.13888. Epub 2016 Sep 5. No abstract available. PubMed 27593400 ↗
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  • Meshaal SS, El Hawary RE, Abd Elaziz DS, Eldash A, Alkady R, Lotfy S, Mauracher AA, Opitz L, Pachlopnik Schmid J, van der Burg M, Chou J, Galal NM, Boutros JA, Geha R, Elmarsafy AM. Phenotypical heterogeneity in RAG-deficient patients from a highly consanguineous population. Clin Exp Immunol. 2019 Feb;195(2):202-212. doi: 10.1111/cei.13222. Epub 2018 Nov 4. PubMed 30307608 ↗
  • El Hawary RE, Mauracher AA, Meshaal SS, Eldash A, Abd Elaziz DS, Alkady R, Lotfy S, Opitz L, Galal NM, Boutros JA, Pachlopnik Schmid J, Elmarsafy AM. MHC-II Deficiency Among Egyptians: Novel Mutations and Unique Phenotypes. J Allergy Clin Immunol Pract. 2019 Mar;7(3):856-863. doi: 10.1016/j.jaip.2018.07.046. Epub 2018 Aug 28. PubMed 30170160 ↗
  • Prader S, Felber M, Volkmer B, Truck J, Schwieger-Briel A, Theiler M, Weibel L, Hambleton S, Seipel K, Vavassori S, Pachlopnik Schmid J. Life-Threatening Primary Varicella Zoster Virus Infection With Hemophagocytic Lymphohistiocytosis-Like Disease in GATA2 Haploinsufficiency Accompanied by Expansion of Double Negative T-Lymphocytes. Front Immunol. 2018 Dec 3;9:2766. doi: 10.3389/fimmu.2018.02766. eCollection 2018. PubMed 30564229 ↗
  • Volkmer B, Planas R, Gossweiler E, Lunemann A, Opitz L, Mauracher A, Nuesch U, Gayden T, Kaiser D, Drexel B, Dumrese C, Jabado N, Vavassori S, Pachlopnik Schmid J. Recurrent inflammatory disease caused by a heterozygous mutation in CD48. J Allergy Clin Immunol. 2019 Nov;144(5):1441-1445.e17. doi: 10.1016/j.jaci.2019.07.038. Epub 2019 Aug 13. No abstract available. PubMed 31419545 ↗
  • Mauracher AA, Eekels JJM, Woytschak J, van Drogen A, Bosch A, Prader S, Felber M, Heeg M, Opitz L, Truck J, Schroeder S, Adank E, Klocperk A, Haralambieva E, Zimmermann D, Tantou S, Kotsonis K, Stergiou A, Kanariou MG, Ehl S, Boyman O, Sediva A, Renella R, Schmugge M, Vavassori S, Pachlopnik Schmid J. Erythropoiesis defect observed in STAT3 GOF patients with severe anemia. J Allergy Clin Immunol. 2020 Apr;145(4):1297-1301. doi: 10.1016/j.jaci.2019.11.042. Epub 2019 Dec 17. No abstract available. PubMed 31857100 ↗
  • Ghraichy M, Galson JD, Kovaltsuk A, von Niederhausern V, Pachlopnik Schmid J, Recher M, Jauch AJ, Miho E, Kelly DF, Deane CM, Truck J. Maturation of the Human Immunoglobulin Heavy Chain Repertoire With Age. Front Immunol. 2020 Aug 6;11:1734. doi: 10.3389/fimmu.2020.01734. eCollection 2020. PubMed 32849618 ↗
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  • Fouriki A, Schnider C, Theodoropoulou K, Pachlopnik J, Hofer M, Candotti F. [Newborn screening for severe T and B lymphocyte deficiencies in Switzerland]. Rev Med Suisse. 2021 Jan 13;17(720-1):68-76. French. PubMed 33443835 ↗
  • Hanitsch L, Baumann U, Boztug K, Burkhard-Meier U, Fasshauer M, Habermehl P, Hauck F, Klock G, Liese J, Meyer O, Muller R, Pachlopnik-Schmid J, Pfeiffer-Kascha D, Warnatz K, Wehr C, Wittke K, Niehues T, von Bernuth H. Treatment and management of primary antibody deficiency: German interdisciplinary evidence-based consensus guideline. Eur J Immunol. 2020 Oct;50(10):1432-1446. doi: 10.1002/eji.202048713. Epub 2020 Sep 9. PubMed 32845010 ↗
  • Jagle S, Heeg M, Grun S, Rensing-Ehl A, Maccari ME, Klemann C, Jones N, Lehmberg K, Bettoni C, Warnatz K, Grimbacher B, Biebl A, Schauer U, Hague R, Neth O, Mauracher A, Pachlopnik Schmid J, Fabre A, Kostyuchenko L, Fuhrer M, Lorenz MR, Schwarz K, Rohr J, Ehl S. Distinct molecular response patterns of activating STAT3 mutations associate with penetrance of lymphoproliferation and autoimmunity. Clin Immunol. 2020 Jan;210:108316. doi: 10.1016/j.clim.2019.108316. Epub 2019 Nov 23. PubMed 31770611 ↗
  • Grazioli S, Tavaglione F, Torriani G, Wagner N, Rohr M, L'Huillier AG, Leclercq C, Perrin A, Bordessoule A, Beghetti M, Schmid JP, Vavassori S, Perreau M, Eberhardt C, Didierlaurent A, Kaiser L, Eckerle I, Roux-Lombard P, Blanchard-Rohner G. Immunological Assessment of Pediatric Multisystem Inflammatory Syndrome Related to Coronavirus Disease 2019. J Pediatric Infect Dis Soc. 2021 Aug 14;10(6):706-713. doi: 10.1093/jpids/piaa142. PubMed 33180935 ↗
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  • Dedual MA, Wueest S, Challa TD, Lucchini FC, Aeppli TRJ, Borsigova M, Mauracher AA, Vavassori S, Pachlopnik Schmid J, Bluher M, Konrad D. Obesity-Induced Increase in Cystatin C Alleviates Tissue Inflammation. Diabetes. 2020 Sep;69(9):1927-1935. doi: 10.2337/db19-1206. Epub 2020 Jul 2. PubMed 32616516 ↗
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  • Weins AB, Theiler M, Bogatu B, Kerl K, Pleimes M, Pachlopnik-Schmid J, Weibel L. Febrile ulceronecrotic Mucha-Habermann disease mimicking Kawasaki disease. J Dtsch Dermatol Ges. 2020 Feb;18(2):140-142. doi: 10.1111/ddg.13989. Epub 2019 Dec 9. No abstract available. PubMed 31814284 ↗
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  • Bode SF, Ammann S, Al-Herz W, Bataneant M, Dvorak CC, Gehring S, Gennery A, Gilmour KC, Gonzalez-Granado LI, Gross-Wieltsch U, Ifversen M, Lingman-Framme J, Matthes-Martin S, Mesters R, Meyts I, van Montfrans JM, Pachlopnik Schmid J, Pai SY, Soler-Palacin P, Schuermann U, Schuster V, Seidel MG, Speckmann C, Stepensky P, Sykora KW, Tesi B, Vraetz T, Waruiru C, Bryceson YT, Moshous D, Lehmberg K, Jordan MB, Ehl S; Inborn Errors Working Party of the EBMT. The syndrome of hemophagocytic lymphohistiocytosis in primary immunodeficiencies: implications for differential diagnosis and pathogenesis. Haematologica. 2015 Jul;100(7):978-88. doi: 10.3324/haematol.2014.121608. Epub 2015 May 28. PubMed 26022711 ↗
  • Sepulveda FE, Debeurme F, Menasche G, Kurowska M, Cote M, Pachlopnik Schmid J, Fischer A, de Saint Basile G. Distinct severity of HLH in both human and murine mutants with complete loss of cytotoxic effector PRF1, RAB27A, and STX11. Blood. 2013 Jan 24;121(4):595-603. doi: 10.1182/blood-2012-07-440339. Epub 2012 Nov 16. PubMed 23160464 ↗
  • Vavassori S, Chou J, Faletti LE, Haunerdinger V, Opitz L, Joset P, Fraser CJ, Prader S, Gao X, Schuch LA, Wagner M, Hoefele J, Maccari ME, Zhu Y, Elakis G, Gabbett MT, Forstner M, Omran H, Kaiser T, Kessler C, Olbrich H, Frosk P, Almutairi A, Platt CD, Elkins M, Weeks S, Rubin T, Planas R, Marchetti T, Koovely D, Klambt V, Soliman NA, von Hardenberg S, Klemann C, Baumann U, Lenz D, Klein-Franke A, Schwemmle M, Huber M, Sturm E, Hartleif S, Haffner K, Gimpel C, Brotschi B, Laube G, Gungor T, Buckley MF, Kottke R, Staufner C, Hildebrandt F, Reu-Hofer S, Moll S, Weber A, Kaur H, Ehl S, Hiller S, Geha R, Roscioli T, Griese M, Pachlopnik Schmid J. Multisystem inflammation and susceptibility to viral infections in human ZNFX1 deficiency. J Allergy Clin Immunol. 2021 Aug;148(2):381-393. doi: 10.1016/j.jaci.2021.03.045. Epub 2021 Apr 17. PubMed 33872655 ↗
  • Kannan A, Suomalainen M, Volle R, Bauer M, Amsler M, Trinh HV, Vavassori S, Schmid JP, Vilhena G, Marin-Gonzalez A, Perez R, Franceschini A, Mering CV, Hemmi S, Greber UF. Sequence-Specific Features of Short Double-Strand, Blunt-End RNAs Have RIG-I- and Type 1 Interferon-Dependent or -Independent Anti-Viral Effects. Viruses. 2022 Jun 28;14(7):1407. doi: 10.3390/v14071407. PubMed 35891387 ↗

Individual participant data

Plan to share: Yes — planned publication in peer reviewed journals (PubMed)

08

Registry details

Key details

Study ID
NCT02735824
Lead sponsor
University Children's Hospital, Zurich
Responsible party
Sponsor
First posted
Apr 13, 2016
Start date
Feb 2016
Primary completion
Jul 2027 (estimated)
Completion
Dec 2027 (estimated)
Last update
May 14, 2026

Study contacts

Jana M Pachlopnik Schmid, MD PhD
Contact
jana.pachlopnik@kispi.uzh.ch
+41 44 249 64 70
Jana M Pachlopnik Schmid, MD PhD
principal investigator · University Children's Hospital, Zurich

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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