Synovial tissue immune complexes (ICs) contain citrullinated fibrinogen. (a, b) immunohistochemistry demonstrates co-localisation of fibrinogen, complement component C3 and immunoglobulins in rheumatoid arthritis (RA) pannus tissue. Representative staining of synovium derived from two separate cyclic-citrullinated peptides (CCP) + rheumatoid factor (RF) + RA patients are shown in (a) and (b). Immunohistochemistry was performed on articular cartilage samples derived from RA patients. Samples were fixed, paraffin-embedded and sections stained with antisera specific for complement component C3, fibrinogen and IgG, as well as with matched pre-immune sera. Horseradish peroxidase (HRP)-conjugated secondary antibodies were utilised to detect primary antibody reactivity. These stainings demonstrate co-localisation of complement component C3, fibrinogen and immunoglobulin staining at the surface of the articular cartilage sections. (c) Mass spectrometry analysis of ICs immunoprecipitated from RA synovial tissue demonstrates the presence of citrullinated fibrinogen peptides.