Persistence of circulating T-follicular helper cells after rituximab is associated with relapse of IgG4-related disease

Dear Editor, T-follicular helper (Tfh) cells have been implicated in the pathogenesis of a variety of autoimmune disorders because of their central role in adaptive immune responses [1]. In particular, Tfh cells orchestrate germinal centre reactions by recruiting CXCR5-expressing B-lymphocytes via CXCL13 secretion, and control antigen-dependent maturation, isotype class-switching, and somatic hypermutation of naïve B-cells [1]. IgG4-related disease (IgG4-RD) is an emerging fibro-inflammatory condition characterized by relapsing–remitting tumour-like lesions and increased serum IgG4 concentration [2, 3]. B-lymphocytes play a central pathogenic role in IgG4-RD because active disease is associated with oligoclonal expansion of fibrogenic IgG4+ plasmablasts [4]. In addition, B-cell depletion therapy with rituximab typically leads to rapid clinical improvement and flares occur in parallel with re-emergence of clonally divergent plasmablasts [2–5]. Of note, these B-cell clones are marked by enhanced somatic hypermutation consistent with iterative rounds of...