Neutrophil-binding antibodies are found in some patients with neutropenia and appear to be caused by an underlying disorder in humoral immune regulation. Unfortunately, the syndromes of immune neutropenia are incompletely resolved and thus, a rational therapeutic approach is difficult. The purpose of this project is to measure complement activation by neutrophil-binding antibodies and to attempt to determine the role of this complement activation in immune neutropenia. In this project, neutrophil-binding antibodies will be measured on patients' own cells and in patients' serum by the binding of 125I-Staphylococcal Protein A and by the binding of 125I-mouse monoclonal anti-human IgG. Complement activation by neutrophil-binding IgG will be measured by the binding of 125I-mouse monoclonal anti-human C3 and by the generation of C5a. C5a generation will be detected by leukocyte aggregation and C5a radioimmunoassay. The antibodies or factors in serum which bind complement to leukocytes or activate C5a will be studied by ion-exchange and gel chromatography. The quantitative relationship between IgG-binding and complement-activation will be determined for individual patients. These parameters will then be used to subclassify syndromes of suspected immune neutropenia and to attempt to predict results of therapy. These studies will offer a new experimental approach to the identification and treatment of patients with immune neutropenia.
