Natural History of Individuals With Immune System Problems That Lead to Fungal Infections

NCT01386437 | Recruiting

• 2 other identifiers: 11018711-I-0187
• Study Type: observational
• Target: 1,200
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- The immune system is made up of special cells, tissues, and organs that fight infections. Problems with this system may lead to frequent, severe, or unusual fungal infections. These infections are often difficult to treat. Researchers want to collect blood and tissue samples from people who have unusual, persistent or severe fungal infections or immune problems that increase the risk of these infections. Objectives: \- To collect medical information and samples for a long-term study of people with immune system problems that lead to fungal infections. Eligibility:

• People with a history of fungal infections caused by immune system problems.
• Parents, children, and siblings of this group.
• Healthy volunteers not related to the first two groups. Design:
• This long-term study may last for up to 25 years. Those in the study may need to provide new information about every 6 months. The procedures for each person may vary with the particular diagnosis and the extent of fungal infection. Healthy volunteers may have only one or two visits.
• At the first visit, those in the study will have a full medical history and physical exam. They will also provide blood.
• Research procedures may include the following:
• Saliva, urine or stool testing
• Mouthwash collection for DNA testing
• Collection of cheek cells, nail clippings, or vaginal fluid
• Tests of leftover tissue or body fluid from previous medical procedures
• Skin or oral mucous membrane biopsy
• Collection of white blood cells
• Followup visits will involve a physical exam and updated medical history. Blood, saliva, urine, or nail clipping samples may be taken for ongoing studies. Any additional tests or exams required by the study doctors may also be done.
• Participants may withdraw from the study pool at any time.

Conditions

Chronic Mucocutaneous Candidiasis; Invasive Aspergillosis; CARD9; APECED

Keywords

Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED); Fungal Infections; Molds; Autoimmune Polyendocrinpathy Syndrome (APS) Type 1; Natural History; Mucocutaneous Fungal Infection; Invasive Fungal Infection

Outcome Measures

Primary Outcomes (1)

• Immunological mechanisms of fungal susceptibility

  Characterize and understand the immunological mechanism(s) by which inherited immunodeficiencies or acquired conditions increase susceptibility to mucocutaneous and invasive fungal infections.

  25 years

Secondary Outcomes (2)

• Determine microbiologic test usefullness

  25 years

• Determine immunological profile of mucosal fungal infections

  25 years

Study Arms (1)

Fungal infections

Patients with or without inherited or acquired abnormalities of immune function manifesting mucocutaneous and/or invasive fungal infections

Eligibility Criteria

• Age: 1 Day - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population will be drawn from referrals from the NIH Clinical Center staff, physicians at outside medical facilities, the Clinical Center Volunteer Program, and self-referrals. Patients may be evaluated as inpatients, or at the NIAID outpatient clinic depending on the severity of the clinical manifestations of their infection. The patients genetic relatives will be evaluated at the NIAID outpatient clinic. Patients or relatives who meet the inclusion and/or exclusion criteria, but who are not able to travel to the NIH Clinical Center may be enrolled in the study and evaluated for immune and genetic defects using send-in blood samples or clinical specimens (e.g., previously obtained biopsy specimens or saliva). Healthy volunteers must be seen at NIH and will not have the option to mail in samples.

You may qualify if:

• Patients:
• Adults or children (regardless of age, sex, or ethnicity/race) with a known or yet uncharacterized inherited immunodeficiency and a definitively diagnosed mucocutaneous or invasive fungal infection.
• Adults or children (regardless of age, sex, or ethnicity/race) with acquired immunodeficiency and a severe, unusual, persistent or treatment-refractory chronic mucocutaneous fungal infection.
• Adults or children (regardless of age, sex, or ethnicity/race) with acquired immunodeficiency and a possible, probable or proven invasive fungal infection (European Organization for Research and Treatment of Cancer / Mycoses Study Group criteria).
• Adults or children (regardless of age, sex, or ethnicity/race) with a well-documented prior, unusual, severe, persistent, or treatment-refractory mucocutaneous or invasive fungal infection(s), who have clinically recovered from the fungal infection.
• Adults or children (regardless of age, sex, or ethnicity/race) with confirmed or suspected autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) who have not yet developed CMC.
• Ongoing care by a referring/primary care physician (inside or outside NIH).
• Willing to allow storage of blood and tissue samples for future analyses.
• Willing to allow genetic testing from blood, body fluids or tissue specimens.
• Willing to have HIV testing
• Able to provide informed consent or be accompanied by a parent(s)/legal guardian(s) or legally authorized representative (LAR) who is able to provide informed consent.
• No children under the age of 2 years will be seen at the Clinical Center, however they will be able to participate via mail-in specimens
• Patient Relatives:
• Willing to allow storage of blood and tissue samples for future analyses.
• Willing to allow genetic testing from blood, body fluids or tissue specimens.

You may not qualify if:

• Patients:
• A patient will not be eligible if he/she has any of the following:
• Any condition which, in the investigator's opinion, may interfere with the evaluation of a co-existing abnormality of immunity that is the subject of study under this protocol.
• Any condition which, in the investigator's opinion, places the patient at undue risk by participating in the study.
• Unwillingness to undergo testing or procedures associated with this protocol.
• Patient Relatives:
• A genetically related relative will not be eligible for this study if he/she has any condition which, in the investigator's opinion, may interfere with the evaluation of an immune system abnormality that is the subject of study under this protocol.
• Healthy Volunteers:
• A healthy volunteer will not be eligible if he/she has any of the following:
• HIV infection.
• History of recurrent or severe infections.
• History of an underlying malignancy or receipt of cancer chemotherapy within the past 5 years
• Receipt of systemic corticosteroids or other systemic immunosuppressants or immunomodulators within the past 30 days
• Pregnancy or lactating
• History of heart, lung, kidney disease, or bleeding disorders.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (6)

• Ahonen P, Myllarniemi S, Sipila I, Perheentupa J. Clinical variation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in a series of 68 patients. N Engl J Med. 1990 Jun 28;322(26):1829-36. doi: 10.1056/NEJM199006283222601.

  PMID: 2348835 BACKGROUND

• Atkinson TP, Schaffer AA, Grimbacher B, Schroeder HW Jr, Woellner C, Zerbe CS, Puck JM. An immune defect causing dominant chronic mucocutaneous candidiasis and thyroid disease maps to chromosome 2p in a single family. Am J Hum Genet. 2001 Oct;69(4):791-803. doi: 10.1086/323611. Epub 2001 Aug 21.

  PMID: 11517424 BACKGROUND

• Holland SM, DeLeo FR, Elloumi HZ, Hsu AP, Uzel G, Brodsky N, Freeman AF, Demidowich A, Davis J, Turner ML, Anderson VL, Darnell DN, Welch PA, Kuhns DB, Frucht DM, Malech HL, Gallin JI, Kobayashi SD, Whitney AR, Voyich JM, Musser JM, Woellner C, Schaffer AA, Puck JM, Grimbacher B. STAT3 mutations in the hyper-IgE syndrome. N Engl J Med. 2007 Oct 18;357(16):1608-19. doi: 10.1056/NEJMoa073687. Epub 2007 Sep 19.

  PMID: 17881745 BACKGROUND

• Ferre EMN, Yu Y, Oikonomou V, Hilfanova A, Lee CR, Rosen LB, Burbelo PD, Vazquez SE, Anderson MS, Barocha A, Heller T, Soldatos A, Holland SM, Walkiewicz MA, Lionakis MS. Case report: Discovery of a de novo FAM111B pathogenic variant in a patient with an APECED-like clinical phenotype. Front Immunol. 2023 Feb 17;14:1133387. doi: 10.3389/fimmu.2023.1133387. eCollection 2023.

  PMID: 36875114 DERIVED

• Chascsa DM, Ferre EMN, Hadjiyannis Y, Alao H, Natarajan M, Quinones M, Kleiner DE, Simcox TL, Chitsaz E, Rose SR, Hallgren A, Kampe O, Marko J, Ali RO, Auh S, Koh C, Belkaid Y, Lionakis MS, Heller T. APECED-Associated Hepatitis: Clinical, Biochemical, Histological and Treatment Data From a Large, Predominantly American Cohort. Hepatology. 2021 Mar;73(3):1088-1104. doi: 10.1002/hep.31421.

  PMID: 32557834 DERIVED

• Burbelo PD, Ferre EMN, Chaturvedi A, Chiorini JA, Alevizos I, Lionakis MS, Warner BM. Profiling Autoantibodies against Salivary Proteins in Sicca Conditions. J Dent Res. 2019 Jul;98(7):772-778. doi: 10.1177/0022034519850564. Epub 2019 May 16.

  PMID: 31095438 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Candidiasis, Chronic Mucocutaneous; Polyendocrinopathies, Autoimmune; Mycoses; Invasive Fungal Infections

Condition Hierarchy (Ancestors)

Candidiasis; Bacterial Infections and Mycoses; Infections; Dermatomycoses; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Michail S Lionakis, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michail S Lionakis, M.D.

CONTACT

(301) 443-5089; lionakism@mail.nih.gov

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2011
• First Posted: July 1, 2011
• Study Start: November 5, 2012
• Last Updated: April 28, 2026

Record last verified: 2026-04-23

Locations

US (1)