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

NCT ID: NCT01386437

Last Updated: 2026-02-05

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 1200 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2012-11-05

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.

Detailed Description

This protocol is a natural history study designed to investigate the clinical, microbiologic, genetic and immunologic correlates of primary immune deficiencies and other conditions associated with mucocutaneous and invasive fungal infections (IFIs). The hypothesis is that chronic mucocutaneous mycoses and IFIs are caused by abnormalities in immune function in these patients that can be identified using modern methods in molecular and cell biology and immunology. For inclusion, patients must have a history of or an active mucocutaneous or invasive fungal infection, but may or may not have a defined primary or acquired immunodeficiency state. Patients will undergo evaluations that include history/physical examination and blood, saliva, and possible tissue sampling for genetic and immunological testing. Patient relatives may also be screened for clinical, microbiological, genetic and/or immunological correlates of host defense abnormalities. Healthy volunteers will be enrolled as a source of control blood, saliva, and possible tissue sampling, and for genetic testing.

The aim of this protocol is to use modern methods in molecular and cell biology and immunology to elucidate the immunopathogenesis of fungal disease in humans. A better understanding of primary immunodeficiency and identification of fungal and host risk factors for fungal infection may provide new insights into pathogenesis and identify targets for development of novel therapies. Enrolled subjects may be followed for up to 25 years to undergo additional clinical evaluation and sampling. Follow-up may occur every 6 months or more frequently depending on clinical course, the underlying risk factor(s), and the type of fungal infection. Under some circumstances, standard medical treatment will be provided for a fungal infection or immune deficiency.

Conditions

Chronic Mucocutaneous Candidiasis; Invasive Aspergillosis; CARD9; APECED

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Fungal infections

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

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

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.

OR

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.

OR

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).

OR

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.

OR

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.

Willing to have HIV testing

Able to provide informed consent or, if younger than 18, be accompanied by a parent(s)/legal guardian(s) who is able to provide informed consent.

Healthy Volunteers:

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

NIH employees are eligible

Exclusion Criteria

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.

Any condition which, in the investigator's opinion, may interfere with the comparison of clinical specimens against those obtained from affected subjects.

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michail S Lionakis, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Institute of Allergy and Infectious Diseases (NIAID)

Locations

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Michail S Lionakis, M.D.

Role: CONTACT

lionakism@mail.nih.gov

(301) 443-5089

Facility Contacts

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

Role: primary

ccopr@nih.gov

800-411-1222 ext. TTY dial 711

References

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.

Reference Type: BACKGROUND

PMID: 2348835 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11517424 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17881745 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36875114 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32557834 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31095438 (View on PubMed)

Related Links

https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2011-I-0187.html

NIH Clinical Center Detailed Web Page

Other Identifiers

11-I-0187

Identifier Type: -

Identifier Source: secondary_id

110187

Identifier Type: -

Identifier Source: org_study_id