The altered DNA methylation profile within the MHC class II cluster in ACPA-positive RA, which may affect assembly, expression and peptide loading of HLA genes, would determine the functional capacity of RA-associated HLA class II molecules [32, 33] during presentation of autoantigen-derived peptides to T cells able to drive disease-inducing adaptive immunity (for further details of this scenario and its T and B cell specificities, see references [34–36]). Here, PRTN3 is linked to rheumatoid arthritis.