Cytophilic immunoglobulin G binding on neutrophils from a child with malignant osteopetrosis who developed fatal acute respiratory distress mimicking transfusion-related acute lung injury

Abstract

A 18-month-old boy, diagnosed at age 3 months with osteopetrosis, was treated since age 6 months with rhIFN-γ in combination with rhM-CSF. The child developed acute respiratory distress within 1 hr of a paternal platelet transfusion, Both the child and the father were blood group type O, and platelets were collected the previous day from the father, Chest X-ray revealed right pulmonary consolidation and a complete 'whiteout' on the left. By 24 hr, the lungs had the appearance of adult respiratory distress syndrome (ARDS). Over the course of the next 11 days, the child remained intubated and hypotensive, and died of respiratory insufficiency 11 days later. ARDS was confirmed at autopsy. Pre- and posttransfusion patient's sera, as well as paternal serum, were tested by granulocyte agglutination and flow cytometry against granulocytes (PMN) from the patient, father, mother, and routine cell-panel donors and lymphocytes for the presence of neutrophil-specific and lymphocyte (HLA) antibodies, to rule out classical transfusion-related acute lung injury (TRALI). Both the patient's and the paternal sera were devoid of antibodies, but the patient's neutrophils demonstrated strong binding of cytophilic IgG accompanied by extremely low serum IgG and IgG1 levels. Since rhIFN-γ is known to upregulate Pc gamma receptor type I (FcγRI) with high affinity for IgG1, the binding of cytophilic IgG suggests that the patient's neutrophils may have been activated in vivo. The case report of another child with osteopetrosis has also been described. Although the blood specimen was not available for serological studies, this 4 1/4 -year-old child treated with rhIFN-γ and rhM-CSF also died of adult respiratory distress syndrome, with similar clinical presentations.