Studies of Disorders With Increased Susceptibility to Fungal Infections

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.

Study Overview

• Status: Recruiting
• Conditions: Fungal Infections; Primary Immune Deficiencies

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.

• Study Type: Observational
• Enrollment (Estimated): 850

Contacts and Locations

• Study Contact: Name: Sergio D Rosenzweig, M.D.; Phone Number: (301) 451-8971; Email: srosenzweig@mail.nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center
      • Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR); Phone Number: TTY dial 711 800-411-1222; Email: ccopr@nih.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• 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.

Description

• 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 informed consent 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 hemoglobin 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:

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 HIV, chemotherapeutic agent(s), or an underlying malignancy 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 hepatitis B or C since age 11.

Study Plan

How is the study designed?

Design Details

• Observational Models: Family-Based
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Healthy Voluntary; Healthy voluntary
Patients; affected patient
relatives; family member to patient

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	10 years
Determine the prevalence of mutation	Determine the prevalence of AIRE mutations in patients with increased susceptibility to Candida or other fungal infections.	10 years
genotype-phenotype correlation	Establish a genotype-phenotype correlation in patients with different AIRE mutations.	10 years
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	10 years

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Sergio D Rosenzweig, M.D., National Institute of Allergy and Infectious Diseases (NIAID)

Publications and helpful links

General 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.
• 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.
• 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.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2011

Study Registration Dates

• First Submitted: October 15, 2010
• First Submitted That Met QC Criteria: October 15, 2010
• First Posted (Estimated): October 18, 2010

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Natural History; Diabetic; PID; Candida; Primary Immune Deficiencies; Immune Abnormalities
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Immune System Diseases; Infections; Immunologic Deficiency Syndromes; Bacterial Infections and Mycoses; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Primary Immunodeficiency Diseases; Mycoses; Torulopsis
• Other Study ID Numbers: 100216; 10-I-0216

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No