Download PDF
Exp Clin Endocrinol Diabetes 2020; 128(02): 119-124
DOI: 10.1055/a-0669-9333
Article
© Georg Thieme Verlag KG Stuttgart · New York

Changes in Serum Immunoglobulin G4 Levels in Patients with Newly Diagnosed Graves’ Disease

Izumi Hiratsuka
1   Department of Endocrinology & Metabolism, Fujita Health University School of Medicine 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, Japan
,
Hiroya Yamada
2   Department of Hygiene, Fujita Health University School of Medicine 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, Japan
,
Mitsuyasu Itoh
1   Department of Endocrinology & Metabolism, Fujita Health University School of Medicine 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, Japan
,
Megumi Shibata
1   Department of Endocrinology & Metabolism, Fujita Health University School of Medicine 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, Japan
,
Takeshi Takayanagi
1   Department of Endocrinology & Metabolism, Fujita Health University School of Medicine 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, Japan
,
Masaki Makino
1   Department of Endocrinology & Metabolism, Fujita Health University School of Medicine 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, Japan
,
Yoshihisa Sugimura
1   Department of Endocrinology & Metabolism, Fujita Health University School of Medicine 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, Japan
,
Nobuki Hayakawa
3   Clinical Pharmacotherapeutics I, Faculty of Pharmacy, Meijo University, 1-501 Shiogamaguchi, Tempaku-ku, Nagoya, Aichi, Japan
,
Shuji Hashimoto
2   Department of Hygiene, Fujita Health University School of Medicine 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, Japan
,
Atsushi Suzuki
1   Department of Endocrinology & Metabolism, Fujita Health University School of Medicine 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, Japan
› Author Affiliations Funding: This work was supported by JSPS KAKENHI Grant Number 17K18220.
Further Information

Publication History

received 06 June 2018
revised  28 July 2018

accepted 06 August 2018

Publication Date:
20 September 2018 (online)

Also available at
    Permissions and Reprints

Abstract

Objective Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is an immune-mediated condition that can affect almost any organ. We investigated the association between IgG4-RD and the main characteristics of Graves’ disease (GD) at the time of diagnosis. Additionally, we evaluated whether serum IgG4 levels change during treatment.

Design and patients Twenty-eight patients with newly diagnosed GD were enrolled into this longitudinal follow-up study. Serum IgG4 levels and thyroid function were measured in all the participants at the time of diagnosis. Further, the serum IgG4 levels of nine of 28 patients with untreated GD were measured after the achievement of euthyroid state (through the use of methimazole).

Results Two (7.1%) of 28 patients with untreated GD had elevated serum IgG4 levels of >135 mg/dL. There was no significant difference in the average IgG4 levels before and after the achievement of euthyroid state (66.2±74.0 mg/dL vs. 50.5±47.3 mg/dL). In two patients, the elevated serum IgG4 levels returned to normal after treatment. However, one patient had an elevated serum IgG4 level of 136.6 mg/dL after treatment.

Conclusions This study showed that serum IgG4 levels varied with treatment in patients with GD, independent of thyroid function, suggesting that IgG4 might be indirectly related to GD.

Key words

serum IgG4 level - thyroid - longitudinal study - IgG4-RD
 

  • References

  • 1 Kuś A, Szymański K, Peeters RP. et al. The association of thyroid peroxidase antibody risk loci with susceptibility to and phenotype of Graves’ disease. Clin Endocrinol (Oxf) 2015; 83: 556-562
    CrossrefPubMedSearch in Google Scholar
  • 2 Hiratsuka I, Yamada H, Munetsuna E. et al. Circulating microRNAs in Graves' disease in relation to clinical activity. Thyroid 2016; 26: 1431-1440
    CrossrefPubMedSearch in Google Scholar
  • 3 Yamada H, Itoh M, Hiratsuka I. et al. Circulating microRNAs in autoimmune thyroid diseases. Clin Endocrinol (Oxf) 2014; 81: 276-281
    CrossrefPubMedSearch in Google Scholar
  • 4 Hamano H, Kawa S, Horiuchi A. et al. High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med 2001; 344: 732-738
    CrossrefPubMedSearch in Google Scholar
  • 5 Stone JH, Khosroshahi A, Deshpande V. et al. Recommendations for the nomenclature of IgG4-related disease and its individual organ system manifestations. Arthritis Rheum 2012; 64: 3061-3067
    CrossrefPubMedSearch in Google Scholar
  • 6 Li Y, Bai Y, Liu Z. et al. Immunohistochemistry of IgG4 can help subclassify Hashimoto's autoimmune thyroiditis. Pathol Int 2009; 59: 636-641
    CrossrefPubMedSearch in Google Scholar
  • 7 Li Y, Nishihara E, Hirokawa M. et al. Distinct clinical, serological, and sonographic characteristics of Hashimoto's thyroiditis based with and without IgG4-positive plasma cells. J Clin Endocrinol Metab 2010; 95: 1309-1317
    CrossrefPubMedSearch in Google Scholar
  • 8 Dahlgren M, Khosroshahi A, Nielsen GP. et al. Riedel’s thyroiditis and multifocal fibrosclerosis are part of the IgG4-related systemic disease spectrum. Arthritis Care Res (Hoboken) 2010; 62: 1312-1318
    PubMedSearch in Google Scholar
  • 9 Pusztaszeri M, Triponez F, Pache JC. et al. Riedel’s thyroiditis with increased IgG4 plasma cells: Evidence for an underlying IgG4-related sclerosing disease?. Thyroid 2012; 22: 964-968
    CrossrefPubMedSearch in Google Scholar
  • 10 Takeshima K, Inaba H, Ariyasu H. et al. Clinicopathological features of Riedel's thyroiditis associated with IgG4-related disease in Japan. Endocr J 2015; 62: 725-731
    CrossrefPubMedSearch in Google Scholar
  • 11 Takeshima K, Inaba H, Furukawa Y. et al. Elevated serum immunoglobulin G4 levels in patients with Graves' disease and their clinical implications. Thyroid 2014; 24: 736-743
    CrossrefPubMedSearch in Google Scholar
  • 12 Bozkirli E, Bakiner OS, Ersozlu Bozkirli ED. et al. Serum Immunoglobulin G4 levels are elevated in patients with Graves' ophthalmopathy. Clin Endocrinol 2015; 83: 962-967
    CrossrefPubMedSearch in Google Scholar
  • 13 Hiratsuka I, Itoh M, Yamada H. et al. Simultaneous measurement of serum chemokines in autoimmune thyroid diseases: Possible role of IP-10 in the inflammatory response. Endocr J 2015; 62: 1059-1066
    CrossrefPubMedSearch in Google Scholar
  • 14 Umehara H, Okazaki K, Masaki Y. et al. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol 2012; 22: 21-30
    CrossrefPubMedSearch in Google Scholar
  • 15 Torimoto K, Okada Y, Kurozumi A. et al. Clinical features of patients with Basedow’s disease and high serum IgG4 levels. Intern Med 2017; 56: 1009-1013
    CrossrefPubMedSearch in Google Scholar
  • 16 Carruthers MN, Khosroshahi A, Augustin T. et al. The diagnostic utility of serum IgG4 concentrations in IgG4-related disease. Ann Rheum Dis 2015; 74: 14-18
    CrossrefPubMedSearch in Google Scholar
  • 17 Khosroshahi A, Stone JH. A clinical overview of IgG4-related systemic disease. Curr Opin Rheumatol 2011; 23: 57-66
    CrossrefPubMedSearch in Google Scholar
  • 18 Zen Y, Nakanuma Y. IgG4-related disease: A cross-sectional study of 114 cases. Am J Surg Pathol 2010; 34: 1812-1819
    CrossrefPubMedSearch in Google Scholar
  • 19 Aucouturier P, Danon F, Daveau M. et al. Measurement of serum IgG4 levels by a competitive immunoenzymatic assay with monoclonal antibodies. J Immunol Methods 1984; 74: 151-162
    CrossrefPubMedSearch in Google Scholar
  • 20 Carballo I, Alvela L, Pérez LF. et al. Serum concentrations of IgG4 in the Spanish adult population: Relationship with age, gender, and atopy. PLoS One 2016; 11: e0149330
    CrossrefPubMedSearch in Google Scholar
  • 21 Aalberse RC, Stapel SO, Schuurman J. et al. Immunoglobulin G4: An odd antibody. Clin Exp Allergy 2009; 39: 469-477
    CrossrefPubMedSearch in Google Scholar
  • 22 Nirula A, Glaser SM, Kalled SL. et al. What is IgG4? A review of the biology of a unique immunoglobulin subtype. Curr Opin Rheumatol 2011; 23: 119-124
    CrossrefPubMedSearch in Google Scholar
  • 23 Koike T. IgG4-related disease: Why high IgG4 and fibrosis?. Arthritis Res Ther 2013; 15: 103
    CrossrefPubMedSearch in Google Scholar
  • 24 Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med 2012; 366: 539-551
    CrossrefPubMedSearch in Google Scholar
  • 25 Phenekos C, Vryonidou A, Gritzapis AD. et al. Th1 and Th2 serum cytokine profiles characterize patients with Hashimoto’s thyroiditis (Th1) and Graves’ disease (Th2). Neuroimmunomodulation 2004; 11: 209-213
    CrossrefPubMedSearch in Google Scholar
  • 26 Wakelkamp IMMJ, Gerding MN, van der Meer JWC. et al. Both Th1- and Th2- derived cytokines in serum are elevated in Graves’ ophthalmopathy. Clin Exp Immunol 2000; 121: 453-457
    CrossrefPubMedSearch in Google Scholar
  • 27 Salvi M, Pedrazzoni M, Girasole G. et al. Serum concentrations of proinflammatory cytokines in Graves’ disease: Effect of treatment, thyroid function, ophthalmopathy and cigarette smoking. Eur J Endocrinol 2000; 143: 197-202
    PubMedSearch in Google Scholar
  • 28 Miyauchi S, Matsuura B, Onji M. Increased levels of serum interleukin-18 in Graves’ disease. Thyroid 2000; 10: 815-819
    CrossrefPubMedSearch in Google Scholar
  • 29 Yamamoto K, Itoh M, Okamura T. et al. Relative levels of the inflammatory cytokine TNFα and the soluble CD40 ligand profile in serum correlate with the thyrotoxic activity of Graves’ Diseases. Thyroid 2012; 2: 516-521
    PubMedSearch in Google Scholar