CYTOPHILIC IMMUNOGLOBULIN-G BINDING ON NEUTROPHILS FROM A CHILD WITH MALIGNANT OSTEOPETROSIS WHO DEVELOPED FATAL ACUTE RESPIRATORY-DISTRESSMIMICKING TRANSFUSION-RELATED ACUTE LUNG INJURY

A 16-month-old boy, diagnosed at age 3 months with osteopetrosis, was treated since age 6 months with rhIFN-gamma in combination with rhM-CS F. The child developed acute respiratory distress within 1 hr of a pat ernal platelet transfusion. Both the child and the father were blood g roup type O, and platelets were collected the previous day from the fa ther. Chest X-ray revealed right pulmonary consolidation and a complet e ''whiteout'' on the left. By 24 hr, the lungs had the appearance of adult respiratory distress syndrome (ARDS). Over the course of the nex t 11 days, the child remained intubated and hypotensive, and died of r espiratory insufficiency 11 days later. ARDS was confirmed at autopsy. Pre-and posttransfusion patient's sera, as well as paternal serum, we re tested by granulocyte agglutination and flow cytometry against gran ulocytes (PMN) from the patient, father, mother, and routine cell-pane l donors and lymphocytes for the presence of neutrophil-specific and l ymphocyte (HLA) antibodies, to rule out classical transfusion-related acute lung injury (TRALI). Both the patient's and the paternal sera we re devoid of antibodies, but the patient's neutrophils demonstrated st rong binding of cytophilic IgG accompanied by extremely low serum IgG and IgG1 levels. Since rhIFN-gamma is known to upregulate Pc gamma rec eptor type I (Fc gamma RI) with high affinity for IgG1, the binding of cytophillic IgG suggests that the patient's neutrophils may have been activated in vive. The case report of another child with osteopetrosi s has also been described. Although the blood specimen was not availab le for serological studies, this 41/2-year-old child treated with rhIF N-gamma and rhM-CSF also died of adult respiratory distress syndrome, with similar clinical presentations. (C) 1996 Wiley-Liss, Inc.