Natural History of Individuals With Immune System Problems That Lead to Fungal Infections
Natural History of Individuals With Immune System Problems That Lead to Fungal Infections
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 10 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.
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 10 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.
-  INCLUSION CRITERIA:

 Patients:

 Patients with or without inherited or acquired abnormalities of immune function manifesting
 mucocutaneous and/or invasive fungal infections are eligible for screening and assessment
 under this protocol. Specifically, patients must meet all the following inclusion criteria
 in order to participate in this study:

 Adults or children (regardless of age, gender 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, gender 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, gender 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, gender 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, gender 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

 For Clinical Center inpatients unable to give informed consent due to an illness or
 cognitive incapacity, a Durable Power of Attorney (DPA) must be available 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:

 Individuals (regardless of age, gender or ethnicity/race) who are genetically related to
 the patient (e.g., mother, father, siblings, children) may be recruited to establish the
 genetic origin of immune defects that may be identified in the study patients at the
 discretion of the PI. Relatives must meet all the following inclusion criteria in order to
 participate in this study:

 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

 Healthy Volunteers:

 Healthy adults regardless of gender and ethnicity/race between the ages of 18 and 85 years
 old may be eligible to participate in this study. Healthy volunteers must meet all the
 following inclusion criteria in order to participate in this study:

 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.

 Hemoglobin of < 7 gm/dL. If a patient is enrolled solely to obtain left-over pathology
 specimens, saliva, a buccal sample, skin swab, vaginal swab, or a stool sample, this
 exclusion criteria will not apply as there will be no blood withdrawal.

 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/immunomodulators
 within the past 30 days

 Pregnancy or lactating

 History of heart, lung, kidney disease, or bleeding disorders.