Adhesion molecules, endogenous granulocyte colony-stimulating factor levels and replating capacity of progenitors in autoimmune neutropenia of childhood.
OBJECTIVE
To investigate the role of granulocyte colony-stimulating factor (G-CSF) and adhesion molecules and the response of bone marrow to peripheral cytopenia in autoimmune neutropenia of childhood (AIN).


METHODS
Thirty-five children with AIN, 25 with acute leukaemia in remission, 10 of whom developed chemotherapy-associated neutropenia, and 28 non-neutropenic age-matched children were studied. The methods included haemopoietic progenitor cells' colony growth, replating of colony-forming unit-granulocyte macrophage (CFU-GM) of the 7th day and ELISA for the detection of serum levels of cytokines and adhesion molecules.


RESULTS
In cases of severe autoimmune neutropenia, haemopoietic progenitors showed increased proliferative capacity compared to the control group (p = 0.03). Intercellular adhesion molecule-1 (ICAM-1), E-selectin, tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) levels inversely correlated with neutrophil counts (r = -0.8, p < 0.001 for ICAM-1, r = -0.5, p = 0.04 for E-selectin, r = -0.58, p = 0.01 for TNF-alpha, r = -0.62, p = 0.04 for IL-1beta). Serum ICAM-1, TNF-alpha and IL-1beta levels correlated positively with G-CSF levels (r = 0.47, p = 0.03 for ICAM-1, r = 0.65, p = 0.01 for TNF-alpha, r = 0.67, p = 0.04 for IL-1beta). Serum G-CSF levels were widely distributed and did not correlate with neutrophil counts (r = -0.44, p = 0.09). In secondary neutropenias the respective levels were lower than those in autoimmune neutropenia.


CONCLUSIONS
Haemopoietic progenitors show increased proliferative capacity in cases of severe autoimmune neutropenia. G-CSF seems to act as an inducer of endothelium activation. The degree of neutropenia correlates with serum ICAM-1, E-selectin, TNF-alpha and IL-1beta levels, indicating the existence of an activated endothelium and presumably of a latent, low-grade, inflammatory process in severe autoimmune neutropenia.
Perdikogianni
Ch
Ch
Department of Paediatric Haematology/Oncology, University Hospital of Heraklion Crete, Greece.
Dimitriou
H
H
Stiakaki
E
E
Markaki
E A
EA
Kalmanti
M
M
D001327:Autoimmune Diseases / Q000097:blood*; D015815:Cell Adhesion Molecules / Q000097:blood*; D002675:Child, Preschool; D003114:Colony-Forming Units Assay; D019040:E-Selectin / Q000097:blood; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007223:Infant; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D007375:Interleukin-1 / Q000097:blood; D008297:Male; D009503:Neutropenia / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor