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

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 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.

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

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.