Congenital neutropenia: studies of pathogenesis

Congenital neutropenia (CN) was diagnosed in a five-month-old boy. A variety of studies was performed to define the pathogenesis of his disease. Opsonic antineutrophil antibodies wre present in his serum. Transfused normal granulocytes circulated poorly. Incubation of the patient's serum with normal granulocytes failed to alter their metabolic or functional activity. The patient's marrow demonstrated increased numbers of colony-forming units (CFUs) in vitro compared with control marrow. The patient's parents had low marrow CFU activity. The patient's serum and peripheral lymphocytes failed to inhibit normal marrow CFU activity. The patient's marrow did inhibit CFU growth of an HLA-identical-sibling's marrow in coculture. Histocompatibility studies demonstrated the HLA-B12 antigen in this patient, a histocompatibility marker previously associated with CN. These studies suggest some cases of CN are associated with a genetically transmitted marrow factor capable of suppressing myelopoiesis in normal marrow.