Studies of Disorders With Increased Susceptibility to Fungal Infections

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.

- 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)