The Role of EBV and Immune Deregulation in the Development of IgG4-Related Diseases

IgG4-related disease (IgG4-RD) is a recently recognized multi-organ fibro-inflammatory condition characterized by a tendency to form mass lesions in multiple sites, a dense lymphoplasmacytic infiltrate dominated by IgG4+ plasma cells, storiform fibrosis, and elevated serum IgG4 levels. Recent papers have discussed the potential role played by EBV in some cases of IgG4-RD. The aim of this review is to highlight the possible interaction between EBV-induced immune deregulation and the development of IgG4-RD, discussing also about the prognostic implications. A systematic review was conducted using studies sourced from the PubMed, Embase, and Cochrane literature databases. A total of 10 relevant publications discussing IgG4-RD associated with EBV infection were analyzed. Reactivation of EBV seems to play a role in the development of IgG4-RD and seems also to affect the prognosis of the disease. Searching EBV DNA copy number or testing EBV-encoded RNA (EBER) in situ hybridization to detect EBV in tissues could be prognostically relevant in patients with features of IgG4-RD, especially in presence of systemic or unusual manifestations. However, further investigations are required to better clarify the pathogenetic link between EBV and IgG4-RD.