Mutations in the Fc-region of IgG from synovial fluids of patients with rheumatoid arthritis

Abstract

Rheumatoid arthritis an antigen-driven autoimmune disease and the eliciting antigens are unknown. They should be present in immune complexes of synovial fluids. The immune complexes were isolated from synovial fluids of patients with rheumatoid arthritis and analyzed by polyacrylamide gel electrophoresis and Western blotting. Immune complexes contained IgG as major protein. The antibodies dissociated at pH 2.5 and self-aggregated upon neutralization. In ELISA assays, they had the highest specificity to homologous IgG, less to normal IgG and lowest of heterologous arthritic IgG confirming earlier results that altered IgG structures were antigenic. Sequencing of the Fc-regions revealed mutations in all patients analyzed. Therefore, mutations within the Fc-regions of IgG could be antigens in rheumatoid arthritis. We propose that methods should be developed to prove this hypothesis.

Keywords:

• rheumatoid arthritis
• IgG Fc-region
• mutations
• immune complexes
• rheumatoid factor

Public interest statement

Rheumatoid arthritis is a desastrous progressive autoimmune disease for which no causative cure is available, simply because the eliciting antigens are unknown despite intesive research efforts. Most patients have also Rheumatiod factor activity where antibodies bind to their own structures within the constant region. Here we considered, wether mutations in the constant regions of immunoglobulins could represent the eliciting antigens.

Competing Interests

The authors declare no competing interest.

Additional information

Notes on contributors

Peter Prehm

Dr Peter Prehm is a retired professor from the Institute of Physiological Chemistry and Pathobiochemistry at the University Hospital Münster, Germany. His research interests are the biochemistry of glycosaminoglycans with particular emphasis on hyaluronan and pathobiochemical disturbances.