Background and objective: Cohen syndrome is a multiple congenital anomalies-mental retardation syndrome associated with granulocytopenia. To date, the mechanisms involved in causing the neutropenia are unknown. In order to get insight into the mechanisms of neutropenia, we studied both the bone marrow and the functional properties of neutrophils obtained from peripheral blood (PB) or skin window (SW) exudate of a patient affected by Cohen syndrome.
Design and methods: Assays of superoxide anion release (as reduction of cytochrome C) and cell adhesion (quantified by measuring membrane acid phosphatase) were carried out according to a microplate method whereby both parameters can be evaluated (Bellavite et al., 1992). Neutrophil surface integrins and CD62L (selectin) were evaluated by flow cytometry.
Results: Bone marrow did not show relevant morphological abnormalities in either erythroid or myeloid precursors. Cohen neutrophils exhibited a greater adhesive capability than control leukocytes in all the conditions studied (PB or SW, unstimulated or agonist-stimulated leukocytes). Cytofluorometric evaluation of neutrophil beta 2 integrin (CD11b) and selectin (CD62L) showed a lower mean fluorescence intensity and a lower percentage of fluorescence conjugate monoclonal Ab-positive cells in the patient than in control subjects. Moreover, a double population of neutrophils, with different affinities to the specific monoclonal antibody anti-CD11b, was observed in the patient. Superoxide anion release, expression and distribution of fluorescence conjugate MoAb anti-human CD11a were normal.
Interpretation and conclusions: Neutrophil adhesive capability was greatly increased in a case of Cohen syndrome. Cytofluorimetric expression of CD11b and CD62L molecules was consistent with a generalized neutrophil activation in vivo.