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RecruitingNCT01222741Updated Oct 16, 2026

Studies of Disorders With Increased Susceptibility to Fungal Infections

An observational study in Fungal Infections and Primary Immune Deficiencies, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Recruiting at 1 site in United States. Open to participants aged 18 Years to 85 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-10-16.

Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Observational

From the registry’s dates

  • Started Jan 2011; still recruiting 15 years 10 months later.
Study type
Observational
Model
Family-based
Time perspective
Prospective
Enrollment
850
Ages
18 Years to 85 Years
Sex
All
01

Study summary

Background:

- Researchers are interested in studying disorders that make individuals more susceptible to fungal infections, specifically infections with the Candida yeast. These disorders are often related to problems with the immune system and may have genetic factors, which suggests that researchers should study not only the individual with the disorder, but also his or her first- and second-degree relatives (such as parents, siblings, children, and first cousins). To provide material for future research, individuals with immune disorders and their first- and second-degree relatives will be asked to provide blood and other samples for testing and comparison with samples taken from healthy volunteers with no history of immune disorders.

Objectives:

- To collect blood and other biological samples to study immune disorders that make individuals more susceptible to fungal infections.

Eligibility:

  • Individuals of any age who have abnormal immune function characterized by recurrent or unusual fungal infections, recurrent or chronic inflammation, or other types of immune dysfunction.
  • First- or second-degree genetically related family members (limited to mother, father, siblings, grandparents, children, aunts, uncles, and first cousins).
  • Healthy volunteers at least 18 years of age (for comparison purposes).

Design:

  • Participants will provide blood samples and buccal (cells from the inside of the mouth near the cheek) samples.
  • Participants with immune disorders will also be asked to provide urine samples, saliva or mucosal samples, or skin tissue biopsies, and may also have imaging studies (such as x-rays) to collect information for research.
  • Samples may be collected at the National Institutes of Health or at other clinical locations for the samples to the sent to the National Institutes of Health.
  • No treatment will be provided as part of this protocol.
Read the detailed description

This study is designed for the evaluation, diagnosis, and long-term follow up of selected patients with primary immune deficiencies and other conditions associated with fungal, and more specifically with Candida spp. infections. The primary immune deficiencies to be studied include, but are not limited to, autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), chronic mucocutaneous candidiasis (CMC), myeloperoxidase deficiency (MPO), immune dysregulation polyendocrinopathy enteropathy X-linked (IPEX), Job s syndrome, chronic granulomatous disease (CGD), biotinidase deficiency, Ikaros zinc finger 1 (IKAROS)-associated diseases, and Interferon Regulatory Factor 4 (IRF4) deficiency. Diabetic patients and infants also show increased susceptibility to such infections and might be studied. Patient participants will undergo evaluations that include history/physical, blood sampling, genetic testing, and possible tissue sampling. We may use some of the blood cells to investigate the utility of induced pluripotent stem cells (iPS) for immune cell derivation and targeted gene correction. Relative participants who are first or second degree genetically related family members of patients (limited to mother, father, siblings, grandparents, children, aunts, uncles, and first cousins) might also be screened for clinical, in vitro, and genetic correlates of immune abnormalities. Healthy volunteers will be enrolled as a source of control samples for research testing. Among the aims of this protocol are to better understand the genetic and pathophysiologic factors that lead to defects in host defense, and to use modern and evolving methods in molecular and cellular biology to elucidate the pathogenesis of this particular susceptibility. A better understanding of primary immunodeficiency could allow for the rational development of novel therapies for such diseases and to benefit future patients, but it might not benefit current patient participants directly. Routine follow-up may occur every 6 months with evaluation and blood sampling. Under some circumstances, we may provide medically indicated standard treatments for the immune deficiencies under study, and we will collect information from clinically indicated care for research purposes.

02

Conditions studied

  • Fungal Infections
  • Primary Immune Deficiencies

Keywords

  • PID
  • Primary Immune Deficiencies
  • Candida
  • Immune Abnormalities
  • Diabetic
  • Natural History
03

In context

Mycoses

260 studies on the registry are indexed under Mycoses; 37 are open to participants now.

This study's planned enrollment of 850 is above the median of 153 across 85 observational studies indexed under Mycoses.

Browse Mycoses studies →

Lead sponsor

National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,446 studies on the registry; 179 are open to participants now.

Of its 405 completed or terminated interventional studies of FDA-regulated products, 302 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 85 Years
Sexes eligible
All
Accepts healthy volunteers
Yes
Sampling method
Non-probability sample

Study population

patients with primary immune deficiencies, their first and second-degree blood relatives (relatives), and individuals with other conditions that result in increased susceptibility to Candida spp. infections. This study will also include healthy volunteer adults as a source of control samples.

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

Patients

To be eligible to participate in this study as a patient, an individual must meet the following criteria:

  • Be 2 years of age to be seen at the Clinical Center as an outpatient. Children \<=3 years of age must not have severe infections, as assessed by the investigator, to be seen at the Clinical Center. Send-in samples may be submitted by participants >30 days of age.
  • Have an abnormality of immune function as manifested by recurrent or unusual fungal infections, recurrent or chronic inflammation, or previous laboratory evidence of immune dysfunction. Of particular focus of this study are patients with:

    • APECED
    • CMC
    • MPO
    • IPEX
    • Hyper-immunoglobulin E syndrome (Job s syndrome)
    • CGD
    • Biotinidase deficiency
    • IKAROS defects
    • AIOLOS defects
    • IRF4 defects
    • Other conditions showing increased susceptibility to such infections as described in infants and type 1 diabetic patients
  • Have a primary physician outside of the NIH.
  • Agree to have blood stored for future research.
  • Ability of subject or Legally Authorized Representative (LAR) to understand and the willingness to sign a written document.

Relatives

To be eligible to participate in this study as a relative, an individual must meet the following criteria:

  • Be 2 years of age to be seen at the Clinical Center as an outpatient. Children \<=3 years of age must not have severe infections, as assessed by the investigator, to be seen at the Clinical Center. Send-in samples may be submitted for participants >30 days of age.
  • Be a mother, father, sibling, child, grandparent, aunt, uncle, or first cousin to a patient participant.
  • Adult relatives must be able to provide informed consent.
  • Agree to have blood stored for future research.

Healthy volunteers

To be eligible to participate in this study as a healthy volunteer, an individual must meet the following criteria:

  • Be 18 to 85 years old.
  • Have a count of >11 g/dL.
  • Weigh >=110 pounds.
  • Be able to provide informed consent.
  • Be willing to have blood stored for future research.

Exclusion criteria

EXCLUSION CRITERIA:

Patients and Relatives

In general, there are no strict exclusion criteria for these cohorts. However, the presence of certain types of acquired abnormalities of immunity solely due to , chemotherapeutic agent(s), or an underlying could be grounds for possible exclusion for a patient or relative. In the opinion of the investigator, the presence of such disease processes may interfere with evaluation of a co-existing abnormality of immunity that is the subject of study under this protocol. Pregnant females will not be allowed to participate in any procedure that may be dangerous to the pregnancy or the fetus.

Healthy volunteers

An individual who meets any of the following criteria will be excluded from participation as a healthy volunteer in this study:

  • Is receiving chemotherapeutic agent(s) or has an underlying malignancy.
  • Is pregnant.
  • Has a history of heart, lung, or kidney disease, or bleeding disorders.
  • Has HIV or viral hepatitis (B or C), or history of viral or C since age 11.
Terms in these criteria, in plain language(5)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

Hepatitis B tests

Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.

Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.

05

Study design

Observational model
Family-based
Time perspective
Prospective
Enrollment
850 participants (estimated)

Groups and cohorts

  • Healthy Voluntary

    Healthy voluntary

  • Patients

    affected patient

  • relatives

    family member to patient

06

What researchers measure

Primary outcomes

  1. characterization

    Characterize and compare the clinical and laboratory features of APECED, CMC, and other primary immunodeficiencies or particular conditions (such as infancy or diabetic subjects) with increased susceptibility to Candida or other fungal infections.

    Time frame: 10 years

  2. Determine the prevalence of mutation

    Determine the prevalence of AIRE mutations in patients with increased susceptibility to Candida or other fungal infections.

    Time frame: 10 years

  3. genotype-phenotype correlation

    Establish a genotype-phenotype correlation in patients with different AIRE mutations.

    Time frame: 10 years

  4. Determine and compare the functionality

    Determine and compare the functional integrity of Th17, Dectin1, and AIRE pathways in patients with increased susceptibility to Candida or other fungal infections with and without AIRE mutations

    Time frame: 10 years

07

Study locations

1 of 1 sites recruiting
  • National Institutes of Health Clinical Center
    Bethesda, Maryland 20892, United States
    Recruiting
    • For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) · Contactccopr@nih.gov · 800-411-1222
08

References and documents

Publications

  • Glocker EO, Hennigs A, Nabavi M, Schaffer AA, Woellner C, Salzer U, Pfeifer D, Veelken H, Warnatz K, Tahami F, Jamal S, Manguiat A, Rezaei N, Amirzargar AA, Plebani A, Hannesschlager N, Gross O, Ruland J, Grimbacher B. A homozygous CARD9 mutation in a family with susceptibility to fungal infections. N Engl J Med. 2009 Oct 29;361(18):1727-35. doi: 10.1056/NEJMoa0810719. PubMed 19864672 ↗
  • Plantinga TS, van der Velden WJ, Ferwerda B, van Spriel AB, Adema G, Feuth T, Donnelly JP, Brown GD, Kullberg BJ, Blijlevens NM, Netea MG. Early stop polymorphism in human DECTIN-1 is associated with increased candida colonization in hematopoietic stem cell transplant recipients. Clin Infect Dis. 2009 Sep 1;49(5):724-32. doi: 10.1086/604714. PubMed 19614557 ↗
  • Perheentupa J. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. J Clin Endocrinol Metab. 2006 Aug;91(8):2843-50. doi: 10.1210/jc.2005-2611. Epub 2006 May 9. PubMed 16684821 ↗

Individual participant data

Plan to share: Undecided

09

Updates

2 registry updates since Sep 25, 2026
Minor edits
Nothing that changes what the study is or who can join. Edited: description
2 updates, last Oct 16, 2026
Show all 2 updates
  1. Oct 16, 2026
    Minor edits only
    + 1 other change: description
  2. Oct 13, 2026
    Minor edits only
    + 1 other change: description

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT01222741
Responsible party
Sponsor
First posted
Oct 18, 2010
Start date
Jan 7, 2011
Last update
Oct 16, 2026

Study contacts

Sergio D Rosenzweig, M.D.
Contact
srosenzweig@mail.nih.gov
(301) 451-8971
Sergio D Rosenzweig, M.D.
principal investigator · National Institute of Allergy and Infectious Diseases (NIAID)

Oversight

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

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