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Published in: Arthritis Research & Therapy 1/2016

Open Access 01-12-2016 | Research article

Enhanced IgG4 production by follicular helper 2 T cells and the involvement of follicular helper 1 T cells in the pathogenesis of IgG4-related disease

Authors: Mitsuhiro Akiyama, Hidekata Yasuoka, Kunihiro Yamaoka, Katsuya Suzuki, Yuko Kaneko, Harumi Kondo, Yoshiaki Kassai, Keiko Koga, Takahiro Miyazaki, Rimpei Morita, Akihiko Yoshimura, Tsutomu Takeuchi

Published in: Arthritis Research & Therapy | Issue 1/2016

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Abstract

Background

The aim of this study was to elucidate the function of circulating follicular helper T (Tfh) cell subsets in helping B cells in patients with active, untreated IgG4-related disease (IgG4-RD) and determine their relationship with disease activity.

Methods

Seventeen consecutive patients with active, untreated IgG4-RD, 20 with primary Sjögren syndrome (pSS), 5 with multicentric Castleman’s disease (MCD), and 12 healthy controls (HC) were enrolled. Tfh cell subset function was evaluated by co-culture with naïve B cells in vitro. Activated Tfh cell subsets were defined as a CCR7lowPD-1high subset among Tfh cell subsets. Disease activity was evaluated by IgG4-RD responder index (IgG4-RD RI) score.

Results

The number of Tfh2 cells was significantly higher in IgG4-RD compared to pSS, MCD, or HC, and correlated with serum IgG4 level or the number of plasmablasts. In vitro, Tfh2 cells more efficiently induced the differentiation of naïve B cells into plasmablasts compared to Tfh1 or Tfh17 cells. Of note, while IgG production in culture supernatants of Tfh2 cells was comparable between IgG4-RD and HC, IgG4 production was significantly higher with Tfh2 cells from patients with IgG4-RD than in those from HC. Accordingly, the IgG4:IgG ratio in culture supernatants was also significantly higher with Tfh2 cells from IgG4-RD compared to HC. Moreover, the number of activated Tfh2 cells was higher in IgG4-RD compared to pSS, MCD, or HC, and strongly correlated with IgG4-RD RI score in the baseline active phase. Particularly, the number of activated Tfh2 cells was associated with the number of affected organs and serum IgG4 level. Importantly, the number of activated Tfh2 cells was decreased after glucocorticoid treatment and paralleled disease improvement. Moreover, the number of activated Tfh1 cells was also increased in IgG4-RD compared to pSS, MCD, or HC, correlating with IgG4-RD RI score, but not with serum IgG4 level.

Conclusions

Tfh2 cells, but not Tfh1 or Tfh17 cells, induce the differentiation of naïve B cells into plasmablasts and enhanced production of IgG4 in patients with active, untreated IgG4-RD. Furthermore, activated Tfh2 cells reflect disease activity, suggesting the involvement of this T cell subset in the pathogenesis of IgG4-RD. Interestingly, the number of activated Tfh1 cells was also increased in IgG4-RD, correlating with disease activity but not with serum IgG4 level, suggesting the involvement of Tfh1 cells but not in the process of IgG4 production in patients with IgG4-RD.
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Literature
2.
go back to reference Islam AD, Selmi C, Datta-Mitra A, Sonu R, Chen M, Gershwin ME, et al. The changing faces of IgG4-related disease: clinical manifestations and pathogenesis. Autoimmun Rev. 2015;14:914–22.CrossRefPubMed Islam AD, Selmi C, Datta-Mitra A, Sonu R, Chen M, Gershwin ME, et al. The changing faces of IgG4-related disease: clinical manifestations and pathogenesis. Autoimmun Rev. 2015;14:914–22.CrossRefPubMed
4.
go back to reference Umehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T, et al. A novel clinical entity, IgG4-related disease (IgG4RD): general concept and details. Mod Rheumatol. 2012;22:1–14.CrossRefPubMed Umehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T, et al. A novel clinical entity, IgG4-related disease (IgG4RD): general concept and details. Mod Rheumatol. 2012;22:1–14.CrossRefPubMed
5.
go back to reference Masaki Y, Dong L, Kurose N, Kitagawa K, Morikawa Y, Yamamoto M, et al. Proposal for a new clinical entity, IgG4-positive multiorgan lymphoproliferative syndrome: analysis of 64 cases of IgG4-related disorders. Ann Rheum Dis. 2009;68:1310–5.CrossRefPubMed Masaki Y, Dong L, Kurose N, Kitagawa K, Morikawa Y, Yamamoto M, et al. Proposal for a new clinical entity, IgG4-positive multiorgan lymphoproliferative syndrome: analysis of 64 cases of IgG4-related disorders. Ann Rheum Dis. 2009;68:1310–5.CrossRefPubMed
6.
go back to reference Yamamoto M, Takahashi H, Sugai S, Imai K. Clinical and pathological characteristics of Mikulicz’s disease (IgG4-related plasmacytic exocrinopathy). Autoimmun Rev. 2005;4:195–200.CrossRefPubMed Yamamoto M, Takahashi H, Sugai S, Imai K. Clinical and pathological characteristics of Mikulicz’s disease (IgG4-related plasmacytic exocrinopathy). Autoimmun Rev. 2005;4:195–200.CrossRefPubMed
7.
go back to reference Sato Y, Kojima M, Takata K, Morito T, Asaoku H, Takeuchi T, et al. Systemic IgG4-related lymphadenopathy: a clinical and pathologic comparison to multicentric Castleman’s disease. Mod Pathol. 2009;22:589–99.CrossRefPubMed Sato Y, Kojima M, Takata K, Morito T, Asaoku H, Takeuchi T, et al. Systemic IgG4-related lymphadenopathy: a clinical and pathologic comparison to multicentric Castleman’s disease. Mod Pathol. 2009;22:589–99.CrossRefPubMed
8.
go back to reference Sato Y, Kojima M, Takata K, Morito T, Mizobuchi K, Tanaka T, et al. Multicentric Castleman’s disease with abundant IgG4-positive cells: a clinical and pathological analysis of six cases. J Clin Pathol. 2010;63:1084–9.CrossRefPubMed Sato Y, Kojima M, Takata K, Morito T, Mizobuchi K, Tanaka T, et al. Multicentric Castleman’s disease with abundant IgG4-positive cells: a clinical and pathological analysis of six cases. J Clin Pathol. 2010;63:1084–9.CrossRefPubMed
9.
go back to reference Takeuchi M, Sato Y, Takata K, Kobayashi K, Ohno K, Iwaki N, et al. Cutaneous multicentric Castleman’s disease mimicking IgG4-related disease. Pathol Res Pract. 2012;208:746–9.CrossRefPubMed Takeuchi M, Sato Y, Takata K, Kobayashi K, Ohno K, Iwaki N, et al. Cutaneous multicentric Castleman’s disease mimicking IgG4-related disease. Pathol Res Pract. 2012;208:746–9.CrossRefPubMed
10.
go back to reference Izumi Y, Takeshita H, Moriwaki Y, Hisatomi K, Matsuda M, Yamashita N, et al. Multicentric Castleman disease mimicking IgG4-related disease: a case report. Mod Rheumatol. 2014;1–4. [Epub ahead of print]. Izumi Y, Takeshita H, Moriwaki Y, Hisatomi K, Matsuda M, Yamashita N, et al. Multicentric Castleman disease mimicking IgG4-related disease: a case report. Mod Rheumatol. 2014;1–4. [Epub ahead of print].
11.
go back to reference Ogoshi T, Kido T, Yatera K, Oda K, Kawanami T, Ishimoto H, et al. Assessment of pathologically diagnosed patients with Castleman’s disease associated with diffuse parenchymal lung involvement using the diagnostic criteria for IgG4-related disease. Lung. 2013;191:575–83.CrossRefPubMed Ogoshi T, Kido T, Yatera K, Oda K, Kawanami T, Ishimoto H, et al. Assessment of pathologically diagnosed patients with Castleman’s disease associated with diffuse parenchymal lung involvement using the diagnostic criteria for IgG4-related disease. Lung. 2013;191:575–83.CrossRefPubMed
12.
go back to reference Takenaka K, Takada K, Kobayashi D, Moriguchi M, Harigai M, Miyasaka N. A case of IgG4-related disease with features of Mikulicz’s disease, and retroperitoneal fibrosis and lymphadenopathy mimicking Castleman’s disease. Mod Rheumatol. 2011;21:410–4.CrossRefPubMed Takenaka K, Takada K, Kobayashi D, Moriguchi M, Harigai M, Miyasaka N. A case of IgG4-related disease with features of Mikulicz’s disease, and retroperitoneal fibrosis and lymphadenopathy mimicking Castleman’s disease. Mod Rheumatol. 2011;21:410–4.CrossRefPubMed
13.
go back to reference Wallace ZS, Deshpande V, Mattoo H, Mahajan VS, Kulikova M, Pillai S, et al. IgG4-related disease: clinical and laboratory features in one hundred twenty-five patients. Arthritis Rheumatol. 2015;67:2466–75.CrossRefPubMed Wallace ZS, Deshpande V, Mattoo H, Mahajan VS, Kulikova M, Pillai S, et al. IgG4-related disease: clinical and laboratory features in one hundred twenty-five patients. Arthritis Rheumatol. 2015;67:2466–75.CrossRefPubMed
14.
go back to reference 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;74:190–5.CrossRefPubMed 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;74:190–5.CrossRefPubMed
15.
go back to reference 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;134:679–87.CrossRefPubMedPubMedCentral 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;134:679–87.CrossRefPubMedPubMedCentral
16.
go back to reference Vinuesa CG, Sanz I, Cook MC. Dysregulation of germinal centres in autoimmune disease. Nat Rev Immunol. 2009;9:845–57.CrossRefPubMed Vinuesa CG, Sanz I, Cook MC. Dysregulation of germinal centres in autoimmune disease. Nat Rev Immunol. 2009;9:845–57.CrossRefPubMed
18.
go back to reference 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;71:2011–9.CrossRefPubMed 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;71:2011–9.CrossRefPubMed
19.
go back to reference Morita R, Schmitt N, Bentebibel SE, Ranganathan R, Bourdery L, Zurawski G, et al. Human blood CXCR5(+)CD4(+) T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion. Immunity. 2011;34:108–21.CrossRefPubMedPubMedCentral Morita R, Schmitt N, Bentebibel SE, Ranganathan R, Bourdery L, Zurawski G, et al. Human blood CXCR5(+)CD4(+) T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion. Immunity. 2011;34:108–21.CrossRefPubMedPubMedCentral
20.
go back to reference Akiyama M, Suzuki K, Yamaoka K, Yasuoka H, Takeshita M, Kaneko Y, et al. Number of circulating follicular helper 2 T cells correlates with IgG4 and interleukin-4 levels and plasmablast numbers in IgG4-related disease. Arthritis Rheumatol. 2015;67:2476–81.CrossRefPubMed Akiyama M, Suzuki K, Yamaoka K, Yasuoka H, Takeshita M, Kaneko Y, et al. Number of circulating follicular helper 2 T cells correlates with IgG4 and interleukin-4 levels and plasmablast numbers in IgG4-related disease. Arthritis Rheumatol. 2015;67:2476–81.CrossRefPubMed
21.
go back to reference Akiyama M, Kaneko Y, Yamaoka K, Hayashi Y, Yasuoka H, Suzuki K, et al. Subclinical labial salivary gland involvement in IgG4-related disease affected with vital organs. Clin Exp Rheumatol. 2015;33:949–50.PubMed Akiyama M, Kaneko Y, Yamaoka K, Hayashi Y, Yasuoka H, Suzuki K, et al. Subclinical labial salivary gland involvement in IgG4-related disease affected with vital organs. Clin Exp Rheumatol. 2015;33:949–50.PubMed
22.
go back to reference Simpson N, Gatenby PA, Wilson A, Malik S, Fulcher DA, Tangye SG, et al. Expansion of circulating T cells resembling follicular helper T cells is a fixed phenotype that identifies a subset of severe systemic lupus erythematosus. Arthritis Rheum. 2010;62:234–44.CrossRefPubMed Simpson N, Gatenby PA, Wilson A, Malik S, Fulcher DA, Tangye SG, et al. Expansion of circulating T cells resembling follicular helper T cells is a fixed phenotype that identifies a subset of severe systemic lupus erythematosus. Arthritis Rheum. 2010;62:234–44.CrossRefPubMed
26.
go back to reference He J, Tsai LM, Leong YA, Hu X, Ma CS, Chevalier N, et al. Circulating precursor CCR7(lo)PD-1(hi) CXCR5+ CD4+ T cells indicate Tfh cell activity and promote antibody responses upon antigen reexposure. Immunity. 2013;39:770–81.CrossRefPubMed He J, Tsai LM, Leong YA, Hu X, Ma CS, Chevalier N, et al. Circulating precursor CCR7(lo)PD-1(hi) CXCR5+ CD4+ T cells indicate Tfh cell activity and promote antibody responses upon antigen reexposure. Immunity. 2013;39:770–81.CrossRefPubMed
27.
go back to reference Umehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T, et al. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol. 2012;22:21–30.CrossRefPubMed Umehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T, et al. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol. 2012;22:21–30.CrossRefPubMed
28.
go back to reference Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, et al. Classification criteria for Sjögren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis. 2002;61:554–8.CrossRefPubMedPubMedCentral Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, et al. Classification criteria for Sjögren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis. 2002;61:554–8.CrossRefPubMedPubMedCentral
29.
go back to reference Nishimoto N, Kanakura Y, Aozasa K, Johkoh T, Nakamura M, Nakano S, et al. Humanized anti-interleukin-6 receptor antibody treatment of multicentric Castleman disease. Blood. 2005;106:2627–32.CrossRefPubMed Nishimoto N, Kanakura Y, Aozasa K, Johkoh T, Nakamura M, Nakano S, et al. Humanized anti-interleukin-6 receptor antibody treatment of multicentric Castleman disease. Blood. 2005;106:2627–32.CrossRefPubMed
31.
go back to reference Matsubayashi H, Uesaka K, Kanemoto H, Asakura K, Kakushima N, Tanaka M, et al. Soluble IL-2 receptor, a new marker for autoimmune pancreatitis. Pancreas. 2012;41:493–6.CrossRefPubMed Matsubayashi H, Uesaka K, Kanemoto H, Asakura K, Kakushima N, Tanaka M, et al. Soluble IL-2 receptor, a new marker for autoimmune pancreatitis. Pancreas. 2012;41:493–6.CrossRefPubMed
32.
go back to reference Nakatsuka Y, Handa T, Nakamoto Y, Nobashi T, Yoshihuji H, Tanizawa K, et al. Total lesion glycolysis as an IgG4-related disease activity marker. Mod Rheumatol. 2015;25:579–84.CrossRefPubMed Nakatsuka Y, Handa T, Nakamoto Y, Nobashi T, Yoshihuji H, Tanizawa K, et al. Total lesion glycolysis as an IgG4-related disease activity marker. Mod Rheumatol. 2015;25:579–84.CrossRefPubMed
33.
go back to reference Abe A, Takano K, Seki N, Jitsukawa S, Yamamoto M, Takahashi H, et al. The clinical characteristics of patients with IgG4-related disease with infiltration of the labial salivary gland by IgG4-positive cells. Mod Rheumatol. 2014;24:949–52.CrossRefPubMed Abe A, Takano K, Seki N, Jitsukawa S, Yamamoto M, Takahashi H, et al. The clinical characteristics of patients with IgG4-related disease with infiltration of the labial salivary gland by IgG4-positive cells. Mod Rheumatol. 2014;24:949–52.CrossRefPubMed
34.
go back to reference Motokura T, Kobayashi Y, Fujita A, Nakamura Y, Taniguchi T, Uchimaru K, et al. Clinical significance of serial measurement of serum levels of soluble interleukin-2 receptor and soluble CD8 in malignant lymphoma. Leuk Lymphoma. 1995;16:355–62.CrossRefPubMed Motokura T, Kobayashi Y, Fujita A, Nakamura Y, Taniguchi T, Uchimaru K, et al. Clinical significance of serial measurement of serum levels of soluble interleukin-2 receptor and soluble CD8 in malignant lymphoma. Leuk Lymphoma. 1995;16:355–62.CrossRefPubMed
35.
go back to reference Miyake K, Moriyama M, Aizawa K, Nagano S, Inoue Y, Sadanaga A, et al. Peripheral CD4+ T cells showing a Th2 phenotype in a patient with Mikulicz’s disease associated with lymphadenopathy and pleural effusion. Mod Rheumatol. 2008;18:86–90.CrossRefPubMed Miyake K, Moriyama M, Aizawa K, Nagano S, Inoue Y, Sadanaga A, et al. Peripheral CD4+ T cells showing a Th2 phenotype in a patient with Mikulicz’s disease associated with lymphadenopathy and pleural effusion. Mod Rheumatol. 2008;18:86–90.CrossRefPubMed
36.
go back to reference Kanari H, Kagami S, Kashiwakuma D, Oya Y, Furuta S, Ikeda K, et al. Role of Th2 cells in IgG4-related lacrimal gland enlargement. Int Arch Allergy Immunol. 2010;152:47–53.CrossRefPubMed Kanari H, Kagami S, Kashiwakuma D, Oya Y, Furuta S, Ikeda K, et al. Role of Th2 cells in IgG4-related lacrimal gland enlargement. Int Arch Allergy Immunol. 2010;152:47–53.CrossRefPubMed
37.
go back to reference 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;45:1538–46.CrossRefPubMed 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;45:1538–46.CrossRefPubMed
38.
go back to reference 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;64:254–63.CrossRefPubMed 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;64:254–63.CrossRefPubMed
39.
go back to reference 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;40:1120–30.CrossRefPubMed 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;40:1120–30.CrossRefPubMed
40.
go back to reference Akiyama M, Suzuki K, Kassai Y, Miyazaki T, Morita R, Yoshimura A, et al. Resolution of elevated circulating regulatory T cells by corticosteroids in patients with IgG4-related dacryoadenitis and sialoadenitis. Int J Rheum Dis. 2016;19:430–2.CrossRefPubMed Akiyama M, Suzuki K, Kassai Y, Miyazaki T, Morita R, Yoshimura A, et al. Resolution of elevated circulating regulatory T cells by corticosteroids in patients with IgG4-related dacryoadenitis and sialoadenitis. Int J Rheum Dis. 2016;19:430–2.CrossRefPubMed
41.
go back to reference Good-Jacobson KL, Szumilas CG, Chen L, Sharpe AH, Tomayko MM, Shlomchik MJ. PD-1 regulates germinal center B cell survival and the formation and affinity of long-lived plasma cells. Nat Immunol. 2010;11:535–42.CrossRefPubMedPubMedCentral Good-Jacobson KL, Szumilas CG, Chen L, Sharpe AH, Tomayko MM, Shlomchik MJ. PD-1 regulates germinal center B cell survival and the formation and affinity of long-lived plasma cells. Nat Immunol. 2010;11:535–42.CrossRefPubMedPubMedCentral
42.
go back to reference Arai Y, Yamashita K, Kuriyama K, Shiokawa M, Kodama Y, Sakurai T, et al. Plasmacytoid dendritic cell activation and IFN-α production are prominent features of murine autoimmune pancreatitis and human IgG4-related autoimmune pancreatitis. J Immunol. 2015;195:3033–44.CrossRefPubMed Arai Y, Yamashita K, Kuriyama K, Shiokawa M, Kodama Y, Sakurai T, et al. Plasmacytoid dendritic cell activation and IFN-α production are prominent features of murine autoimmune pancreatitis and human IgG4-related autoimmune pancreatitis. J Immunol. 2015;195:3033–44.CrossRefPubMed
43.
go back to reference Mashima E, Inoue A, Sakuragi Y, Yamaguchi T, Sasaki N, Hara Y, et al. Nivolumab in the treatment of malignant melanoma: review of the literature. Onco Targets Ther. 2015;8:2045–51.PubMedPubMedCentral Mashima E, Inoue A, Sakuragi Y, Yamaguchi T, Sasaki N, Hara Y, et al. Nivolumab in the treatment of malignant melanoma: review of the literature. Onco Targets Ther. 2015;8:2045–51.PubMedPubMedCentral
44.
go back to reference Terawaki S, Chikuma S, Shibayama S, Hayashi T, Yoshida T, Okazaki T, et al. IFN-α directly promotes programmed cell death-1 transcription and limits the duration of T cell-mediated immunity. J Immunol. 2011;186:2772–9.CrossRefPubMed Terawaki S, Chikuma S, Shibayama S, Hayashi T, Yoshida T, Okazaki T, et al. IFN-α directly promotes programmed cell death-1 transcription and limits the duration of T cell-mediated immunity. J Immunol. 2011;186:2772–9.CrossRefPubMed
45.
go back to reference Sah RP, Chari ST. Serologic issues in IgG4-related systemic disease and autoimmune pancreatitis. Curr Opin Rheumatol. 2011;23:108–13.CrossRefPubMed Sah RP, Chari ST. Serologic issues in IgG4-related systemic disease and autoimmune pancreatitis. Curr Opin Rheumatol. 2011;23:108–13.CrossRefPubMed
46.
go back to reference Carruthers MN, Khosroshahi A, Augustin T, Deshpande V, Stone JH. The diagnostic utility of serum IgG4 concentrations in IgG4-related disease. Ann Rheum Dis. 2015;74:14–8.CrossRefPubMed Carruthers MN, Khosroshahi A, Augustin T, Deshpande V, Stone JH. The diagnostic utility of serum IgG4 concentrations in IgG4-related disease. Ann Rheum Dis. 2015;74:14–8.CrossRefPubMed
47.
go back to reference Le Pottier L, Devauchelle V, Fautrel A, Daridon C, Saraux A, Youinou P, et al. Ectopic germinal centers are rare in Sjogren’s syndrome salivary glands and do not exclude autoreactive B cells. J Immunol. 2009;182:3540–7.CrossRefPubMed Le Pottier L, Devauchelle V, Fautrel A, Daridon C, Saraux A, Youinou P, et al. Ectopic germinal centers are rare in Sjogren’s syndrome salivary glands and do not exclude autoreactive B cells. J Immunol. 2009;182:3540–7.CrossRefPubMed
48.
go back to reference Yajima H, Yamamoto M, Shimizu Y, Sakurai N, Suzuki C, Naishiro Y, et al. Loss of interleukin-21 leads to atrophic germinal centers in multicentric Castleman’s disease. Ann Hematol. 2016;95:35–40.CrossRefPubMed Yajima H, Yamamoto M, Shimizu Y, Sakurai N, Suzuki C, Naishiro Y, et al. Loss of interleukin-21 leads to atrophic germinal centers in multicentric Castleman’s disease. Ann Hematol. 2016;95:35–40.CrossRefPubMed
49.
go back to reference Fajgenbaum DC, van Rhee F, Nabel CS. HHV-8-negative, idiopathic multicentric Castleman disease: novel insights into biology, pathogenesis, and therapy. Blood. 2014;123:2924–33.CrossRefPubMed Fajgenbaum DC, van Rhee F, Nabel CS. HHV-8-negative, idiopathic multicentric Castleman disease: novel insights into biology, pathogenesis, and therapy. Blood. 2014;123:2924–33.CrossRefPubMed
50.
go back to reference Okazaki K, Uchida K, Ohana M, Nakase H, Uose S, Inai M, et al. Autoimmune related pancreatitis is associated with autoantibodies and a Th1/Th2-type cellular immune response. Gastroenterology. 2000;118:573–81.CrossRefPubMed Okazaki K, Uchida K, Ohana M, Nakase H, Uose S, Inai M, et al. Autoimmune related pancreatitis is associated with autoantibodies and a Th1/Th2-type cellular immune response. Gastroenterology. 2000;118:573–81.CrossRefPubMed
51.
go back to reference Ohta N, Makihara S, Okano M, Kurakami K, Ishida A, Furukawa T, et al. Roles of IL-17, Th1, and Tc1 cells in patients with IgG4-related sclerosing sialadenitis. Laryngoscope. 2012;122:2169–74.CrossRefPubMed Ohta N, Makihara S, Okano M, Kurakami K, Ishida A, Furukawa T, et al. Roles of IL-17, Th1, and Tc1 cells in patients with IgG4-related sclerosing sialadenitis. Laryngoscope. 2012;122:2169–74.CrossRefPubMed
52.
go back to reference Vinuesa CG, Linterman MA, Goodnow CC, Randall KL. T cells and follicular dendritic cells in germinal center B-cell formation and selection. Immunol Rev. 2010;237:72–89.CrossRefPubMed Vinuesa CG, Linterman MA, Goodnow CC, Randall KL. T cells and follicular dendritic cells in germinal center B-cell formation and selection. Immunol Rev. 2010;237:72–89.CrossRefPubMed
53.
go back to reference Aalberse RC, Stapel SO, Schuurman J, Rispens T. Immunoglobulin G4: an odd antibody. Clin Exp Allergy. 2009;39:469–77.CrossRefPubMed Aalberse RC, Stapel SO, Schuurman J, Rispens T. Immunoglobulin G4: an odd antibody. Clin Exp Allergy. 2009;39:469–77.CrossRefPubMed
54.
go back to reference Carruthers MN, Topazian MD, Khosroshahi A, Witzig TE, Wallace ZS, Hart PA, et al. Rituximab for IgG4-related disease: a prospective, open-label trial. Ann Rheum Dis. 2015;74:1171–7.CrossRefPubMed Carruthers MN, Topazian MD, Khosroshahi A, Witzig TE, Wallace ZS, Hart PA, et al. Rituximab for IgG4-related disease: a prospective, open-label trial. Ann Rheum Dis. 2015;74:1171–7.CrossRefPubMed
Metadata
Title
Enhanced IgG4 production by follicular helper 2 T cells and the involvement of follicular helper 1 T cells in the pathogenesis of IgG4-related disease
Authors
Mitsuhiro Akiyama
Hidekata Yasuoka
Kunihiro Yamaoka
Katsuya Suzuki
Yuko Kaneko
Harumi Kondo
Yoshiaki Kassai
Keiko Koga
Takahiro Miyazaki
Rimpei Morita
Akihiko Yoshimura
Tsutomu Takeuchi
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2016
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-016-1064-4

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