Immunophenotype involved in IgG4-related disease

Figures & data

Table 1. Immune cells in IgG4-related disease.

Cell type	Involvement in the pathogenesis of IgG4-RD	References
Th2 cells	Th2 responses may result from concomitant atopic manifestations.	Mattoo H. et al. Allergy. 2014 [18]
	IL-33 might contribute to the pathogenesis via aberrant activation of Th2 immune responses.	Furukawa S. et al. Sci Rep. 2017 [20]
Treg cells	Treg cells were frequently found in AIPC by immunohistochemically.	Zen Y. et al. Hepatology. 2007 [25]
	Foxp3-positive cells were higher AIP in patients by immunohistochemically.	Kusuda T. et al. Pancreas. 2011 [27]
	Expression of both Th2 and Treg cells was higher in patients with Mikulicz disease	Tanaka A. et al. Arthritis Rheum. 2012 [30]
Tfh cells	mRNA expression of Bcl-6 in LSGs from patients with IgG4-DS was significantly higher.	Maehara T. et al. Ann Rheum Dis. 2012 [16]
	The number of Tfh2 cells was significantly higher in IgG4-RD	Akiyama M. et al. Arthritis Res Ther. 2016 [17]
	Tfh cells in the peripheral blood reflected the degree of Tfh cells infiltration into the tissue.	Kubo S. et al. Rheumatology (Oxford). 2018 [36]
CD4^+ CTL	CD4^+ CTL were clonally expanded in the IgG4-RD tissue.	Mattoo H. et al. J Allergy Clin Immunol. 2016 [33]
	The pathogenesis of IgG4-DS is associated with tissue infiltration by CD4^+ CTL.	Maehara T. et al. Ann Rheum Dis. 2017 [34]
Plasmablast	The IgG4-RD patients had substantially elevated total plasmablast counts.	Wallace ZS. et al. Ann Rheum Dis. 2015 [14]
	Numbers of plasmablasts, which are largely IgG4^+, are increased in patients with IgG4-RD.	Mattoo H. et al. J Allergy Clin Immunol. 2014 [13]

Figure 1 Scheme of two important clinical findings in patients with IgG4-RD.

Mattoo H, Della-Torre E, Mahajan VS, Stone JH, Pillai S. Circulating Th2 memory cells in IgG4-related disease are restricted to a defined subset of subjects with atopy. Allergy 2014;69(3):399–402.

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Furukawa S, Moriyama M, Miyake K, Nakashima H, Tanaka A, Maehara T, et al. Interleukin-33 produced by M2 macrophages and other immune cells contributes to Th2 immune reaction of IgG4-related disease. Sci Rep. 2017;7:42413.

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Zen Y, Fujii T, Harada K, Kawano M, Yamada K, Takahira M, et al. Th2 and regulatory immune reactions are increased in immunoglobin G4-related sclerosing pancreatitis and cholangitis. Hepatology. 2007;45(6):1538–46.

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Kusuda T, Uchida K, Miyoshi H, Koyabu M, Satoi S, Takaoka M, et al. Involvement of inducible costimulator- and interleukin 10-positive regulatory T cells in the development of IgG4-related autoimmune pancreatitis. Pancreas 2011;40(7):1120–30.

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Tanaka A, Moriyama M, Nakashima H, Miyake K, Hayashida JN, Maehara T, et al. Th2 and regulatory immune reactions contribute to IgG4 production and the initiation of Mikulicz disease. Arthritis Rheum. 2012;64(1):254–63.

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Maehara T, Moriyama M, Nakashima H, Miyake K, Hayashida JN, Tanaka A, et al. Interleukin-21 contributes to germinal centre formation and immunoglobulin G4 production in IgG4-related dacryoadenitis and sialoadenitis, so-called Mikulicz's disease. Ann Rheum Dis. 2012;71(12):2011–9.

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Akiyama M, Yasuoka H, Yamaoka K, Suzuki K, Kaneko Y, Kondo H, et al. Enhanced IgG4 production by follicular helper 2T cells and the involvement of follicular helper 1T cells in the pathogenesis of IgG4-related disease. Arthritis Res Ther. 2016;18:167.

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Kubo S, Nakayamada S, Zhao J, Yoshikawa M, Miyazaki Y, Nawata A, et al. Correlation of T follicular helper cells and plasmablasts with the development of organ involvement in patients with IgG4-related disease. Rheumatology (Oxford). 2018;57(3):514–24.

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Mattoo H, Mahajan VS, Maehara T, Deshpande V, Della-Torre E, Wallace ZS, et al. Clonal expansion of CD4(+) cytotoxic T lymphocytes in patients with IgG4-related disease. J Allergy Clin Immunol. 2016;138(3):825–38.

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Maehara T, Mattoo H, Ohta M, Mahajan VS, Moriyama M, Yamauchi M, et al. Lesional CD4+ IFN-γ+ cytotoxic T lymphocytes in IgG4-related dacryoadenitis and sialoadenitis. Ann Rheum Dis. 2017;76(2):377–85.

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Wallace ZS, Mattoo H, Carruthers M, Mahajan VS, Della Torre E, Lee H, et al. Plasmablasts as a biomarker for IgG4-related disease, independent of serum IgG4 concentrations. Ann Rheum Dis. 2015;74(1):190–5.

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Mattoo H, Mahajan VS, Della-Torre E, Sekigami Y, Carruthers M, Wallace ZS, et al. De novo oligoclonal expansions of circulating plasmablasts in active and relapsing IgG4-related disease. J Allergy Clin Immunol. 2014;134(3):679–87.

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