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Identification of Thyroglobulin and its Isoforms as Target Antigens for IgG4 Thyroiditis

2018; OMICS Publishing Group; Volume: 09; Issue: 05 Linguagem: Inglês

10.4172/2155-9899.1000568

2155-9899

Keiko Inomata, Hironori Kurisaki, Hiroyuki Yamashita, Shinya Sato, Seigo Tachibana, Kennichi Kakudo, Yaqiong Li, Hidenobu Koga, Seiho Nagafuchi,

Neuroendocrine Tumor Research Advances

Background: Immunoglobulin G4-related disease (IgG4-RD) presents a systemic autoimmune disorder affecting various organs either simultaneously or solitarily, characterized by the prominent infiltration of IgG4-positive plasma cells into target organs, usually associated with increased circulating IgG4 concentrations.The disease affects any organ such as pancreas, biliary tract, hypophysis, salivary gland, lung, kidney, meninges, eye, prostate, lymph nodes, retroperitoneum, aorta, skin and thyroid gland.Among them, IgG4 thyroiditis has been recognized as a representative organ-specific form of IgG4-RD.However, the immunologic basis of organ specific involvement of IgG4 thyroiditis including target molecules of autoimmune reactivity to thyroid is not known. Methods:In order to examine the pathogenesis of IgG4 thyroiditis, we histologically examined 53 thyroiditis patients out of 2,436 patients who underwent thyroidectomy.Immunohistochemical staining of IgG and IgG4 was used to determine surface markers of infiltrated lymphocytes.Western blotting followed by MALDI-TOF/MS analysis was conducted to identify target antigens.Results: Among 2,436 histologically examined thyroid disease patients, 53 cases were diagnosed as thyroiditis (2.2%); 38 patients with Hashimoto thyroiditis (HT) (71.7%; 38/53) and 15 patients with Graves' disease (GD) (28.3%; 15/53).Only 19 among 53 cases (35.8%) presented significant lymphoplasmacytic infiltrate rich in IgG4positive plasma cells fulfilling the diagnostic criteria for IgG4 thyroiditis, of which 13 were Hashimoto thyroiditis and 6 were Graves' disease.Only 8 among the 19 (42.1%) had increased serum IgG4 levels.Furthermore, target antigens of IgG4 thyroiditis were identified as thyroglobulin and its isoforms. Conclusion:Since thyroglobulin is an organ-specific protein, the observation is consistent with the solitary nature of IgG4 thyroiditis.Even some patients without increased serum IgG4 develop IgG4 thyroiditis, indicating that increased serum IgG4 is not an indispensable marker of IgG4 thyroiditis.The search for target antigens in IgG4-RD is essentially important to clarify the pathogenesis of IgG4-RD.(tuburointerstitial nephritis), meninges (pachymeningitis), eye (dacryoadenitis, retroorbital pseudotumor), prostate (prostatitis), lymph nodes (Castleman's disease), retroperitoneum (retroperitoneal fibrosis), aorta (inflammatory aortic aneurysm), skin (cutaneous pseudolymphoma) and thyroid gland (Riedel thyroiditis, Hashimoto thyroiditis) [2,3,7].In addition, although many putative autoantigens