The presence of large aggregates of lymphocytes with T/B cell compartmentalization and PNAd+ HEVs (indicating lymphoid neogenesis) in the synovial fluid of patients with rheumatoid arthritis (RA) has been associated with disease severity, the frequency of exacerbations and an inferior response to frontline biological therapies that target TNF [36]. This evidence concerns the gene NTAN1 and rheumatoid arthritis.