DYSHEMATOPOIESIS IN COMBINED IMMUNE-DEFICIENCY WITH CONGENITAL NEUTROPENIA

This report describes a patient with combined immune deficiency associated with congenital neutropenia (CID/CN) and reports a partial characterization of his hematopoietic abnormalities. The CID/CN syndrome described is characterized by neutropenia and by deficiencies in B-lymphoid and T-lymphoid cell number and function. Red cell and platelet counts were normal. In vitro assays indicate that the myeloid lineage was developmentally arrested at the level of the committed monocyte/granulocyte progenitor (CFU-GM), while precursors to the CFU-GM progenitor were normal. In vitro studies showed that the defect in myeloid development was not corrected with G-CSF or GM-CSF. However, combinations of cytokines present in conditioned media from the T-cell lines MO or C5MJ, or defined multiple cytokine combinations containing IL-1, IL-3, GM-CSF, kit ligand, IL-6, and IL-9, restored myelopoiesis in-vitro. In contrast, C5MJ-conditioned media did not correct deficiencies in immune function in the patient's lymphocytes and accessory cells. No abnormalities in the production of G-CSF, GM-CSF, M-CSF, or IL-1 from the patient could be identified to account for the defects in myelopoiesis orimmune function. (C) 1994 Wiley-Liss, Inc.