Background IgG4-related disease (IgG4-RD) is a fibroinflammatory condition that can affect almost any organ, characterized by lymphoplasmocytoid infiltrate, obliterative phlebitis and storiform fibrosis often associated with eosinophilia and increased levels of IgG4. Cytotoxic CD4 T cells producing IL-1b [D1], TGFb1 and IFN-gare detectable in peripheral blood of patients and high IL-18 expression has been found in affected organs.
Objectives To evaluate the role of IL-1 family cytokines in IgG4-RD, by analyzing cytokines and receptors in sera.
Methods Nine patients fulfilling the proposed criteria (Umehara, 2012) for the diagnosis of IgG4-RD were recruited. Cytokines of the IL-1 family (IL-1a, IL-1b, IL-33, IL-18), soluble receptors (sIL-1R1, sIL-1R2, sIL-1R3, sIL-1R4) and antagonists (IL-1Ra, IL-18BP) were measured in sera by multiarray ELISA assay. Free IL-18 was calculated using the law of mass action.
Results Most patients had a multiorgan disease; retroperitoneum, salivary glands, pancreas and lymph nodes were most frequently affected. IL-18 (p=0.007) and free IL-18 (p<0.0001), sIL-1R1 (p=0.0005), sIL-1R2 (p=0.0013), and sIL-1R4 (p=0.0006) were significantly increased in IgG4-RD sera compared with healthy controls.
Conclusions In IgG4-RD patients, at variance with other autoimmune or autoinflammatory conditions, the increase in IL-18 levels is not counterbalanced by IL-18BP, leading to high levels of free IL-18.The free cytokine may affect T cell subset balance and induce IFN-g production. The parallel increase of sIL-1R1 and sIL-1R2 suggests an efficient dampening of inflammatory IL-1bsignaling at the tissue level, while high levels of sIL-1R4 may be associated with vascular remodeling and fibrosis, as observed in animal models of obesity and in human cardiovascular disorders.
Disclosure of Interest None declared