Antibodies to myeloid precursor cells in autoimmune neutropenia.

Antibodies to mature blood neutrophils and to bone marrow myeloid cells have been described in the sera of some patients with apparent autoimmune neutropenia. To further explore the prevalence and specificities of antibodies to myeloid precursor cells, we evaluated sera from 148 patients with suspected autoimmune neutropenia for the presence of antibodies to neutrophils, to cultured myeloid cell lines, and to highly purified bone marrow myeloid progenitor cells. Using an immunofluorescence flow cytometric assay, we identified IgG antibodies in 42 (28%) of these sera that bound specifically to K562 cells, a multilineage cell line originally derived from a patient with chronic myelogenous leukemia. Twenty-two (15%) of the sera also contained IgG antibodies that bound specifically to the primitive myelomonocytic leukemia cell line KG1a. Twenty-five (17%) of the sera had IgG antibodies to myeloid cell lines in the absence of antibodies to mature neutrophils. There was a trend toward more severe neutropenia in patients with antibodies to K562 cells, without antineutrophil antibodies. In further studies, antibodies from 12 sera bound to mononuclear CD34+ cells that had been purified from normal human bone marrow by an immunomagnetic separation procedure. Moreover, two of these sera suppressed the growth of granulocyte-macrophage colony-forming units (CFU-GM) in methylcellulose cultures. The presence of antibodies to primitive hematopoietic cells in the sera of some patients with suspected immune neutropenia suggests that these antibodies may have a role in the pathogenesis of the neutropenia observed.

[1]  E. Thorsby HL-A antigens on human granulocytes studied with cytotoxic iso-antisera obtained by skin grafting. , 2009, Scandinavian journal of haematology.

[2]  M. Cutting,et al.  Effects of anti-CD33 blocked ricin immunotoxin on the capacity of CD34+ human marrow cells to establish in vitro hematopoiesis in long-term marrow cultures. , 1992, Experimental hematology.

[3]  D. Metcalfe,et al.  Demonstration of the origin of human mast cells from CD34+ bone marrow progenitor cells. , 1991, Journal of immunology.

[4]  L. Skibsted,et al.  The frequency of platelet alloantibodies in pregnant women and the occurrence and management of neonatal alloimmune thrombocytopenic purpura. , 1990, Obstetrical & gynecological survey.

[5]  M. Murphy,et al.  Platelet transfusions: the problem of refractoriness. , 1990, Blood reviews.

[6]  M R Clark,et al.  Sequences of complementary DNAs that encode the NA1 and NA2 forms of Fc receptor III on human neutrophils. , 1989, The Journal of clinical investigation.

[7]  D. Stroncek,et al.  Immunoblotting characterization of neutrophil antigenic targets in autoimmune neutropenia , 1989 .

[8]  I. Goldstein,et al.  Characterization of polymorphic forms of Fc receptor III on human neutrophils. , 1989, The Journal of clinical investigation.

[9]  B. Baker,et al.  Humoral and cellular immunosuppression of granulopoiesis in a patient with neutropenia. , 1988, The American journal of medicine.

[10]  Currie,et al.  Antibodies to Granulocyte Precursors in Selective Myeloid Hypoplasia and Other Suspected Autoimmune Neutropenias: Use of HL-60 Cells as Targets , 1987 .

[11]  P. Lalezari,et al.  Autoimmune neutropenia of infancy. , 1986, The Journal of pediatrics.

[12]  H. Chapel,et al.  Anti‐granulocyte opsonic activity and autoimmune neutropenia , 1986, British journal of haematology.

[13]  S. Weitzman,et al.  The severity of immune neutropenia correlates with the maturational specificity of antineutrophil antibodies , 1984, British journal of haematology.

[14]  M. Fackler,et al.  Antigenic analysis of hematopoiesis. III. A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG-1a cells. , 1984, Journal of immunology.

[15]  W. Vainchenker,et al.  Myeloid and megakaryocytic properties of K-562 cell lines. , 1983, Cancer research.

[16]  P. Greenberg,et al.  Pure white-cell aplasia. Antibody-mediated autoimmune inhibition of granulopoiesis. , 1983, The New England journal of medicine.

[17]  M. Housset,et al.  Syndrome of neutrophil agranulocytosis, hypogammaglobulinemia, and thymoma , 1982 .

[18]  H. Koeffler,et al.  An undifferentiated variant derived from the human acute myelogenous leukemia cell line (KG-1). , 1980, Blood.

[19]  J. Fitchen,et al.  Serum Inhibitors of Myelopoiesis , 1980, British journal of haematology.

[20]  H. Koeffler,et al.  Acute myelogenous leukemia: a human cell line responsive to colony-stimulating activity. , 1978, Science.

[21]  D. Golde,et al.  Immune suppression of hematopoiesis. , 1978, The American journal of medicine.

[22]  T. Stossel,et al.  Effects of anti-human neutrophil antibodies in vitro. Quantitative studies. , 1974, The Journal of clinical investigation.

[23]  F. Sieber,et al.  Erythroid colony formation in cultures of mouse and human bone marrow: Analysis of the requirement for erythropoietin by gel filtration and affinity chromatography on agarose‐concanavalin A , 1974, Journal of cellular physiology.

[24]  T. Huizinga,et al.  Biallelic neutrophil Na-antigen system is associated with a polymorphism on the phospho-inositol-linked Fc gamma receptor III (CD16). , 1990, Blood.

[25]  D. Wright [44] Human neutrophil degranulation , 1988 .

[26]  L. Boxer,et al.  Neutropenia and thrombocytopenia: antibodies directed against circulating neutrophils and bone marrow myeloid progenitor cells (CFU-C). , 1986, The American journal of the medical sciences.

[27]  R. Hay American Type Culture Collection catalogue of cell lines and hybridomas , 1985 .

[28]  D. Guerry,et al.  Granulocyte-associated IgG in neutropenic disorders. , 1982, Blood.