Natural History Study for BEN
Natural History Study for BEN
In recent decades, hematologists have noticed that persons of African descent sometimes have
 lower white blood cell counts of a certain type, called granulocytes. These cells help to
 fight infections. The lower number of granulocytes in this situation does not appear to lead
 to more infections, and these individuals do not have any symptoms. This condition is called
 benign ethnic neutropenia (BEN), and is observed in a small percentage of individuals of
 African descent. This study will investigate the condition by studying people with and
 without BEN.

 The goals of this study are to:

 1. identify individuals of African descent with BEN.

 2. determine the effects of two drugs, G-CSF and dexamethasone, on granulocyte production
 and movement.

 3. determine whether there are differences in those with and without BEN in the way genes
 are stimulated after the administration of G-CSF and dexamethasone.

 Study participants will be asked to interview with the research team, undergo physical exams,
 donate a blood sample, and receive G-CSF by injection, followed by dexamethasone (orally)
 about three weeks later. They also will be required to undergo apheresis three times, a
 procedure in which blood is drawn from a donor and separated into its components. Some
 components are retained for research analyses, such as granulocytes, and small amount of
 blood; the remainder is returned by transfusion to the donor. This procedure will be required
 of participants before they receive G-CSF, the day after they receive G-CSF, and the day
 after they receive dexamethasone. Gene messages (mRNA will be isolated from granulocytes, and
 analyzed to better understand granulocyte growth and movement.
Benign ethnic neutropenia (BEN) is defined by peripheral blood absolute neutrophil count less
 than 1.5 x 10 (9) per liter without an increase in infections. This condition has been
 described in individuals of African descent. Although these individuals have normal myeloid
 maturation on bone marrow examinations, they appear to release fewer neutrophils into the
 circulation when stimulated by hydrocortisone, compared to normal controls. This suggests
 that there may be differences in the regulation of neutrophil release or trafficking. In the
 past decade, granulocyte-colony stimulating factor (G-CSF) has been widely used in a variety
 of clinical settings, from patients with chemotherapy-induced neutropenia to normal
 volunteers for peripheral blood stem cell collection. G-CSF, however, has not been used in
 individuals with BEN. Furthermore, gene expression in neutrophil proliferation and
 trafficking has not been studied in these individuals. The purpose of this study are to (1)
 identify individuals with BEN; (2) follow the natural history of BEN; (3) determine if there
 is a familial inheritance pattern; (4) characterize and compare neutrophil response to
 dexamethasone and G-CSF; (5) compare the pattern of neutrophil gene expression by microarray
 analyses; and (6) determine if mutations are present at the DNA level to account for gene
 expression pattern differences in individuals of African descent with and without BEN at
 baseline, post dexamethasone, and post G-CSF stimulation.
-  INCLUSION CRITERIA:

 -  Individuals of African descent of age 5 or greater

 -  Normal renal function: creatinine <1.5 mg/dL and proteinuria <1+

 -  Normal liver function: bilirubin <1.5 mg/dL and transaminases within normal limits

 -  For control subjects: WBC within normal range (3,300-9,600/mm3),
 granulocytes/neutrophils greater than or equal to 2,000/mm3, platelets >150,000/mm3,
 hemoglobin > 11.5g/dL and normal MCV

 -  For benign ethnic neutropenic subjects: two blood counts, at least 1 month apart, with
 granulocytes/neutrophils <1,500/mm3, platelet >150,000/mm3, hemoglobin >12.5g/dL, and
 normal MCV. We will also follow subjects whose neutrophil counts are between 1500 and
 2000/mm3 in a separate cohort periodically (e.g. once every 1-2 years) to see if their
 blood counts behave more like BEN or normal subjects.

 -  Female volunteers of childbearing age should not be pregnant

 -  Meets NIH Department of Transfusion Medicine (DTM) eligibility criteria for blood
 component donation for in vitro research uses (negative serologic tests for syphilis,
 hepatitis B and C, HIV, and HTLV-1)

 -  Ability to give informed consent to participate in the protocol

 EXCLUSION CRITERIA:

 -  Any underlying hematologic disorder including anemia, and sickle cell disease.
 Subjects with thalassemia or sickle cell trait are not excluded.

 -  Current use of corticosteroids, e.g. prednisone, dexamethasone, or hydrocortisone.
 Corticosteroids must be discontinued at least one month prior

 -  Active or chronic viral, bacterial, fungal, or parasitic infection. Any antibiotic use
 should be discontinued at least one month prior

 -  History of autoimmune disease, such as rheumatoid arthritis or systemic lupus
 erythematosus, or positive anti-nuclear antibody (ANA ELISA) of 3 E.U. (ELISA units)
 or greater.

 -  Low B12 or folate levels, or abnormal thyroid function tests

 -  History of cancer or chemotherapy, except squamous carcinoma of the skin and cervical
 carcinoma in situ

 -  Pregnant woman or positive urine pregnancy test

 -  History of clinically significant cardiovascular disease (cardiology consultation may
 be obtained when clinically indicated)

 -  Any positive serum screening test as listed below

 -  Allergy to G-CSF or bacterial E. coli products

 -  Active pulmonary disease or a pulse-ox level of less than 95% on screening exam