Considering these findings with the observations that (1) neutrophils are one of the most abundant cells in the synovium of joints affected by rheumatoid arthritis, (2) they can directly present antigens to CD4+ T cells, and (3) they stimulate B-cell differentiation and antibody production through BAFF/APRIL implicates neutrophils as being key to the loss of immune tolerance and production of pathogenic ACPA. This evidence concerns the gene TNFSF13B and rheumatoid arthritis.