Studies of Disorders With Increased Susceptibility to Fungal Infections

Study Description

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Brief 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.

Condition or disease
Primary Immune Deficiency; Candida; Autoimmune Polyendocrinopathy Candidiasis Ectodermal; Chronic Mucocutaneous Candidiasis (CMC); Fungal Infection

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), and biotinidase deficiency. Diabetic patients and infants also show increased susceptibility to such infections and might be studied. Patient participants (who we will refer to as patients in this study) 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. First or second degree genetically related family members (limited to mother, father, siblings, grandparents, children, aunts, uncles, and first cousins of an affected patient and who we will refer to as relatives in this study) 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 treatment that relates to the immune deficiency. These treatments will follow standard medical practice.

Study Design

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Study Type :	Observational
Estimated Enrollment :	850 participants
Time Perspective:	Prospective
Official Title:	Studies of Disorders With Increased Susceptibility to Fungal Infections
Study Start Date :	September 24, 2010

Groups and Cohorts

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Outcome Measures

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Eligibility Criteria

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	Child, Adult, Senior
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

• INCLUSION CRITERIA:

Patient Participants (or simply Patient):

Patients with abnormalities of immune function as manifested by recurrent or unusual fungal infections, recurrent or chronic inflammation, or previous laboratory evidence of immune dysfunction are eligible for screening and assessment under this protocol. Of particular focus of this study are patients with:

• APECED (autoimmune polyendocrinopathy candidiasis ectodermal dystrophy)
• CMC (chronic mucocutaneous candidiasis)
• MPO (myeloperoxidase deficiency)
• IPEX (immune dysregulation polyendocrinopathy enteropathy X-linked)
• Hyper-immunoglobulin E syndrome (Job s syndrome)
• CGD (chronic granulomatous disease)
• Biotinidase deficiency
• Other conditions showing increased susceptibility to such infections as described in infants and type 1 diabetic patientts

There will be no limit due to age, sex, race, or disability.

All patients must have a primary physician outside of the NIH.

Women of child-bearing potential, or who are pregnant or lactating, may be eligible and will only undergo tests and procedures, and/or receive medications that are of proven minimal risk to the fetus or child. Only diagnostic tests without radiographs will be performed.

All patients will be required to have blood stored for future studies and/or other medical conditions.

Relatives:

Relatives may be mother, father, siblings, children, grandparents, aunts, uncles, and first cousins to a patient participant.

There is no limit due to age, sex, race, or disability.

Relatives will be required to have blood stored for future studies and/or other medical conditions.

Healthy volunteers must:

Be an adult of either sex and between age of 18 and 85 years old

Have a hemoglobin concentration of greater than or equal to 11 g/dL

Weigh greater than or equal to 110 pounds

EXCLUSION CRITERIA:

Patient:

The presence of certain types of acquired abnormalities of immunity solely due to human immunodeficiency virus (HIV), chemotherapeutic agent(s), or an underlying malignancy could be grounds for possible exclusion for a subject.

Relatives:

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 relative.

Healthy volunteers are not eligible if:

Receiving chemotherapeutic agent(s), or have underlying malignancy

Pregnant or lactating

Have history of heart, lung, kidney disease, bleeding or immunologic disorders leading to significant incapacity

Have a history of recurrent or severe infections

Have a history of HIV seropositivity

Have a history of viral hepatitis (B or C)

Contacts and Locations

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

Contact: Nana Kwatemaa, R.N.	(301) 451-7820	nkwatemaa@niaid.nih.gov
Contact: Sergio D Rosenzweig, M.D.	(301) 496-4879	srosenzweig@mail.nih.gov

Locations

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike	Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 prpl@cc.nih.gov

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Principal Investigator:	Sergio D Rosenzweig, M.D.	National Institutes of Health Clinical Center (CC)

More Information

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

NIH Clinical Center Detailed Web Page 

Publications:

Perheentupa J. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. J Clin Endocrinol Metab. 2006 Aug;91(8):2843-50. Epub 2006 May 9.

Halonen M, Eskelin P, Myhre AG, Perheentupa J, Husebye ES, Kämpe O, Rorsman F, Peltonen L, Ulmanen I, Partanen J. AIRE mutations and human leukocyte antigen genotypes as determinants of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy phenotype. J Clin Endocrinol Metab. 2002 Jun;87(6):2568-74.

Lilic D. New perspectives on the immunology of chronic mucocutaneous candidiasis. Curr Opin Infect Dis. 2002 Apr;15(2):143-7. Review.

Responsible Party:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT01222741 History of Changes
Other Study ID Numbers:	100216; 10-I-0216
First Posted:	October 18, 2010
Last Update Posted:	March 29, 2018
Last Verified:	January 22, 2018

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):

AIRE- Autoimmune Regulator Gene; APECED- Autoimmune Polyendocrinopathy-Candidiasis Ectodermal Dystrophy; CGD (Chronic Granulomatous Disease); CMC- Chronic Mucocutaneous Candidiasis

Additional relevant MeSH terms:

Candidiasis; Candidiasis, Chronic Mucocutaneous; Infection; Communicable Diseases; Disease Susceptibility; Mycoses; Immunologic Deficiency Syndromes; Polyendocrinopathies, Autoimmune	Disease Attributes; Pathologic Processes; Immune System Diseases; Dermatomycoses; Skin Diseases, Infectious; Skin Diseases; Endocrine System Diseases; Autoimmune Diseases