New insights into immune cells cross-talk during IgG4-related disease

Immunoglobulin G4-related disease (IgG4-RD) is a newly acknowledged entity, characterized by an immune-mediated fibro-inflammatory process affecting virtually all organs, with infiltration of IgG4⁺ bearing plasma cells. Until today the pathogenesis of IgG4-RD remains unknown. Treatment with anti-CD20 monoclonal antibodies efficiently induced remission and attenuated the secretory phenotype of myofibroblasts responsible of uncontrolled collagen deposition. This supports the pathogenic role of the adaptive immunity, particularly B cell compartment and B cell/T cell interaction. Latest studies have also highlighted the importance of innate immune system that has been underestimated before and the key role of a specific T cell subset, T follicular helper cells that are involved in IgG4-class-switching and plasmablast differentiation. In this review, we aim to review the most recent knowledge of innate immunity, T and B cells involvement in IgG4-RD, and introduce tertiary lymphoid organs (TLO) as a potential marker of relapse in this condition.