Response to: 'Synovial cellular and molecular signatures stratify clinical response to csDMARD therapy and predict radiographic progression in early rheumatoid arthritis patients' by Humby et al

We read with interest the article by Humby et al 1 on the three synovial histological and molecular patterns of rheumatoid arthritis (RA), characterised as predominantly lymphoid, myeloid and fibroid. The body of work emanates from a large and impressive multicentre study with extensive molecular data and showed that in an early, treatment-naive RA cohort, a fibroid pathological subtype was associated with poorer response to conventional synthetic disease modifying antirheumatic drugs compared with myeloid and lymphoid profiles. Positive autoantibody status, including disease-specific anticitrullinated peptide antibodies (ACPA), is heavily weighted in the 2010 RA classification criteria. Furthermore, the top 20 genes implicated in ACPA-positive RA, including major histocompatibility complex (MHC) class II associations, PTPN22, CTLA-4 and others,2 suggest a sequence of events, whereby non-specific antigen citrullination in peripheral tissues and localised autoimmunity leads to dysregulation in adaptive immunity (played out in the primary and secondary lymphoid organs), systemic autoimmunity and ultimately RA disease manifesting primarily as joint synovitis. …