These findings have been the foundation to design the proof-of-concept clinical trial in ACPA-positive patients with RA, aimed at validating the therapeutic potential of a new first-in-class anti-TLR4 monoclonal antibody, NI-0101, and the potential of predictive biomarkers (i.e., TLR4 ligands and in particular, levels of ACPA subtypes in serum) to identify patients more likely to benefit from TLR4 blockade by NI-0101. Here, TLR4 is linked to rheumatoid arthritis.