Direct activation of neutrophil chemiluminescence by rheumatoid sera and synovial fluid

The majority of paired sera and synovial fluids from 21 patients with rheumatoid arthritis produced a rapid chemiluminescent response when incubated with human neutrophils. Synovial fluid gave considerably higher responses than the paired serum specimen. In contrast little or no response was found with paired sera and joint fluid taken from patients with gout, psoriasis, and osteoarthritis and with sera from healthy donors. A similar chemiluminescent response was observed when neutrophils were preincubated with large aggregates of heated human gammaglobulin (HAGG), which were used as a model of immune complexes. Smaller nonreactive aggregates of gammaglobulin became reactive after preincubation with a purified monoclonal rheumatoid factor (mRF) which had a high avidity for aggregated IgG. The addition of this monoclonal rheumatoid factor also caused enhancement of chemiluminescence by rheumatoid sera. Further evidence suggesting that the active material found in these rheumatoid specimens contained complexed immunoglobulin was obtained by indirect immunofluorescence. Neutrophils developed intracellular immunoglobulin inclusions after preincubation in reactive rheumatoid sera but not with nonreactive or normal sera. However, activation of neutrophil chemiluminescence by rheumatoid specimens did not correlate significantly with levels of rheumatoid factor or immune complexes suggesting that the activating complexes were of a particular type. In conclusion we have shown the direct activation of neutrophil chemiluminescence by rheumatoid sera synovial fluid and suggest that the activation is caused by large IgG-containing immune complexes. It is possible that this activation may have important implications in the immunopathogenesis of the rheumatoid inflammatory process.