Inclusion Criteria

- INCLUSION CRITERIA:

A. ALPS Natural History sample size and demographics:

Study size: up to 1000 patients, patients, relatives and normal controls.

Sex Distribution: Male and female

Age range: All ages acceptable

B. Eligibility Criteria for Natural History Study:

1. To be considered as having ALPS, patients must elevated TCR alpha/beta+ CD4-8-
peripheral blood DNT cells (equal to or greater than 1.5 percent of total lymphocytes
or 2.5 percent of CD3+ lymphocytes) in the setting of normal or evalted lymphocyte
counts.

2. A history of chronic (greater than 6 months) non-malignant, non-infectious
lymphadenopathy and/or splenomegaly.

3. Willingness to allow blood, tissue and other samples to be stored.

4. Patients with RALD (RAS associated leukoproliferative disorders) who present with
autoimmunity, lymphadenopathy and/or splenomegaly, with elevated or normal DNT's and
somatic mutations in NRAS and KRAS

C. Eligibility Criteria for Screening potential patients:

1. A history of chronic (greater than 6 months) lymphadenopathy and/or splenomegaly.

2. Willingness to allow blood, tissue and other samples to be stored.

D. Screening criteria for ALPS Relatives:

1. Extended family members of an ALPS patient are eligible for genetic screening to
determine if they carry the mutation found in their family.

2. Willingness to allow blood, tissue and other samples to be stored.

E. 1. Apheresis will be done only on healthy volunteers or patients with ALPS who have
adequate peripheral venous access. Women of childbearing age must have a negative
pregnancy test within 24 hours of the procedure and must not be breast-feeding.

EXCLUSION CRITERIA:

1. Any condition that the Principal Investigator deems to be non-conducive to the research
goals of the study.