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THU0063 IL-1 family cytokines and receptors in IGG4-related disease
  1. R Capecchi1,
  2. P Italiani2,
  3. I Puxeddu1,
  4. F Pratesi1,
  5. A Tavoni3,
  6. D Boraschi2,
  7. P Migliorini1
  1. 1Clinical and Experimental Medicine, Clinical Immunology Unit, university of Pisa, pisa
  2. 2Institute of Protein Biochemistry, National Research Council, Naples
  3. 3Clinical and Experimental Medicine, University of Pisa, Clinical Immunology Unit, university of Pisa, pisa, Italy


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

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