In support of the notion that cFb-IC have a role in TLR4-driven joint inflammation, we observed that the profiling of ACPA-positive RASF and paired serum samples from patients with RA, by their reactivity to cFbα and cFbβ chains, identified the TLR4-dependent subgroup with a greater specificity than ACPA alone. This evidence concerns the gene PRTN3 and rheumatoid arthritis.