Immune complex formation between IgM rheumatoid factor and IgG generated by hyaluronic acid

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Abstract
Immunoglobulin inclusions are regularly detected in granulocytes obtained from the synovial fluid of rheumatoid arthritis (RA) patients. In contrast, granulocytes isolated from the blood of the same patients usually contain no immunoglobulin inclusions. Using the indirect granulocyte phagocytosis test (IGPT), we obtained evidence that this discrepancy can be explained by the finding that hyaluronic acid (HA), a component of synovial fluid, increases the avidity of rheumatoid factor (RF), resulting in the formation of IgG–IgM-RF complexes. The addition of HA to RA sera and subsequent testing by IGPT revealed an increased uptake of the induced immune complexes by these cells, which was dependent on the HA dose. Furthermore, supplementation of normal human serum with purified IgM-RF generated a positive IGPT result in a dose-dependent manner in the presence of HA. We conclude that HA, a component of synovial fluid, might facilitate immune complex formation in the joint cavity, resulting in the inflammatory reaction in the joints of RA patients.