DYSHEMATOPOIESIS IN COMBINED IMMUNE-DEFICIENCY WITH CONGENITAL NEUTROPENIA

This report describes a patient with combined immune deficiency associ ated with congenital neutropenia (CID/CN) and reports a partial charac terization of his hematopoietic abnormalities. The CID/CN syndrome des cribed is characterized by neutropenia and by deficiencies in B-lympho id and T-lymphoid cell number and function. Red cell and platelet coun ts were normal. In vitro assays indicate that the myeloid lineage was developmentally arrested at the level of the committed monocyte/granul ocyte progenitor (CFU-GM), while precursors to the CFU-GM progenitor w ere normal. In vitro studies showed that the defect in myeloid develop ment was not corrected with G-CSF or GM-CSF. However, combinations of cytokines present in conditioned media from the T-cell lines MO or C5M J, or defined multiple cytokine combinations containing IL-1, IL-3, GM -CSF, kit ligand, IL-6, and IL-9, restored myelopoiesis in-vitro. In c ontrast, C5MJ-conditioned media did not correct deficiencies in immune function in the patient's lymphocytes and accessory cells. No abnorma lities in the production of G-CSF, GM-CSF, M-CSF, or IL-1 from the pat ient could be identified to account for the defects in myelopoiesis or immune function. (C) 1994 Wiley-Liss, Inc.