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.
Gasparetto
C
C
Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, NY, NY 10021.
Smith
C
C
Firpo
M
M
Dennig
D
D
Small
T
T
Gillio
A P
AP
Lichtenberg
R
R
O'Reilly
R J
RJ
Moore
M A
MA
D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D001853:Bone Marrow / Q000473:pathology; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D006098:Granulocytes / Q000473:pathology; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000150:complications* / Q000473:pathology; D007231:Infant, Newborn; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D008264:Macrophages / Q000473:pathology; D008297:Male; D009503:Neutropenia / Q000150:complications / Q000151:congenital* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
D016207:Cytokines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor