• INCLUSION CRITERIA:

Patients

Patients must:

1. Have cryptococcosis as determined by information collected from their medical records, telephone interviews, or from a referring physician:

   • histopathology showing cryptococci; or
   • culture of C. neoformans or C. gattii
   • a positive cryptococcal antigen in the serum and/or CSF, together with CSF cell count and chemistry consistent with cryptococcal meningitis.

2. Be over the age of 18 years old.

3. Have a primary physician outside of the NIH.

4. Agree to undergo genetic testing that will include WES and high density SNP arrays as appropriate for possible WES linkage studies.

5. Allow samples to be stored for future research.

6. Pregnant patients will not be excluded. However, research procedures greater than minimal risk including bone marrow biopsy and apheresis would not be performed on pregnant subjects. Otherwise, pregnant patients with cryptococcus would be treated with as per standard of care, minimizing teratogenic potential of drugs and ionizing radiation whenever possible.

Blood Relatives of Patients

Blood relatives must:

1. Be a genetic relative of a patient enrolled in this study
2. Be over the age of 18 years old
3. Agree to undergo genetic testing that may include WES and high density SNP analysis
4. Allow samples to be stored for future research

Healthy Volunteers

Healthy volunteers must:

1. Be between the ages of 18 and 70 years old
2. Allow samples to be stored for future research

EXCLUSION CRITERIA:

Patients

Patients will be excluded for any of the following:

1. The presence of certain types of acquired abnormalities of immunity due to:

   • HIV
   • Cancer chemotherapeutic agent(s)
   • An underlying malignancy could be grounds for possible exclusion of a patient if, in the opinion of the investigator, the underlying disease predisposed the patient to the infection
   • Monoclonal antibody therapy directed against a patient s immune system

2. Any condition that in the opinion of the investigator may interfere with the evaluation of a co-existing abnormality of immunity that is the subject of study under this protocol. For example, we may exclude patients with Cushing s disease that have very high cortisol levels at the time of diagnosis of their cryptococcosis.

Genetic Relatives of Patients

Genetic relatives will be excluded for the following:

-Any condition that in the opinion of the investigator may interfere with evaluation of an immune system abnormality that is the subject of study under this protocol.

Healthy Volunteers

Healthy volunteers will be excluded for any of the following:

1. HIV or viral hepatitis (B or C).
2. History of recurrent or severe infections.
3. History of intravenous drug use.
4. History of engaging in high-risk activities for exposure to HIV.
5. Receiving chemotherapeutic agent(s), immunosuppressants or have underlying malignancy.
6. Pregnancy.
7. Have history of heart, lung, kidney disease, or bleeding disorders.
8. Any condition that in the opinion of the investigator may interfere with evaluation of an immune system abnormality that is the subject of study under this protocol.