Peripheral CD4+ T cells showing a Th2 phenotype in a patient with Mikulicz's disease associated with lymphadenopathy and pleural effusion

Miyake, Katsuhisa; Moriyama, Masafumi; Aizawa, Kumiko; Nagano, Shuji; Inoue, Yasushi; Sadanaga, Atsushi; Nakashima, Hitoshi; Nakamura, Seiji

doi:10.1007/s10165-007-0010-3

Cited by 52 publications

(40 citation statements)

References 19 publications

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“…We previously reported that peripheral CD4 T cells from patients with IgG4-DS have deviation of Th1/Th2 balance to Th2 and elevated expression of Th2-type cytokines,19 suggesting that IgG4-DS has a Th2-predominant phenotype 20. We also demonstrated a close association of IL-4 and IL-10 expression with IgG4 production in the labial salivary glands (LSGs) of patients with IgG4-DS 21 22.…”

mentioning

confidence: 76%

Interleukin-21 contributes to germinal centre formation and immunoglobulin G4 production in IgG4-related dacryoadenitis and sialoadenitis, so-called Mikulicz's disease

Mitsui

Moriyama

Nakashima

et al. 2012

Annals of the Rheumatic Diseases

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146

110

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Objectives Interleukin (IL)-21 is mainly produced by CD4 T helper (Th) cells including Th2, Th17 and follicular helper T (Tfh) cells. Recent studies have reported that IL-21 is involved in the formation of germinal centres (GCs) and class switching of IgG4. It has been suggested that IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS), so-called Mikulicz's disease (MD), is distinct from Sjögren's syndrome (SS) and shows a high frequency of GC formation in salivary glands. In this study the expression of IL-21 in IgG4-DS and SS patients was examined. Methods Twelve patients with IgG4-DS, 15 with SS and 15 healthy subjects were screened for (1) ectopic GC formation in formalin-fixed labial salivary gland (LSG) biopsy samples; (2) expression of IL-21, Th2-, Th17-and Tfh-related molecules (cytokines, chemokine receptors and transcription factors) in LSGs; (3) relationship between IgG4/IgG ratio and mRNA expression of IL-21 in LSGs.Results mRNA expression of IL-21 and Bcl-6 in LSGs from patients with IgG4-DS was significantly higher than in patients with SS and controls. IL-21 and CXCR5 were detected by immunohistochemistry in or around GC in patients with SS and those with IgG4-DS. IL-21 was detected in infiltrating lymphocytes outside GC only in patients with IgG4-DS. Expression of IL-21 was consistent with that of Th2-related molecules while IL-17 was rarely seen in IgG4-DS. Furthermore, the expression of IL-21 in LSGs was correlated with the number of GC formations and the IgG4/IgG ratio in patients with IgG4-DS. Conclusions These results suggest that overexpression of IL-21 by Th2 cells might play a key role in GC formation and IgG4 production in IgG4-DS.

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confidence: 76%

Interleukin-21 contributes to germinal centre formation and immunoglobulin G4 production in IgG4-related dacryoadenitis and sialoadenitis, so-called Mikulicz's disease

Mitsui

Moriyama

Nakashima

et al. 2012

Annals of the Rheumatic Diseases

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146

110

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“…2). Recently, Miyake et al [13] have also reported a case of MD with elevated IgE levels, eosinophilia and an elevated Th2 cytokine expression in peripheral blood mononuclear cells. These findings suggest that Th2 cells are involved in the pathogenesis of IgG4-related diseases.…”

Section: Discussionmentioning

confidence: 99%

“…Regarding the pathogenesis of IgG4-related plasmacytic syndrome, Th2 cells have been reported to be increased at the site of IgG4-related autoimmune pancreatitis [12]. More recently, a case of IgG4-related MD with enhanced Th2 cytokine production was reported [13]. However, the role of Th2 cells and their cytokines in the pathogenesis of IgG4-related diseases is still largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Role of Th2 Cells in IgG4-Related Lacrimal Gland Enlargement

Kanari¹,

Kagami

Kashiwakuma

et al. 2010

Int Arch Allergy Immunol

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Background: Lacrimal gland enlargement (LGE) is one of the characteristics of Mikulicz’s disease (MD). Recently, marked serum IgG4 elevation and infiltration of IgG4-positive plasmacytes in the enlarged exocrine glands have been reported in MD patients. However, little is known about the role of CD4+ T cells and their cytokines in IgG4-related diseases. The aim of this study was to evaluate the characteristics of CD4+ T cells in patients with IgG4-related diseases. Methods: We investigated the clinical characteristics of 9 patients with LGE and elevated serum IgG4 levels (named IgG4-related LGE). We also examined mRNA expression of cytokines and transcription factors of peripheral blood CD4+ T cells in patients with IgG4-related LGE. Results: All patients with IgG4-related LGE showed elevated serum IgE levels. In addition, 5 of 9 patients with IgG4-related LGE exhibited eosinophilia and asthma-like symptoms. In patients with IgG4-related LGE, mRNA expression of IL-4, IL-5, IL-10 and GATA-3 but not IFN-γ or T-bet was enhanced on CD4+ T cells compared with that in healthy controls. Conclusions: Th2 cells may be involved in the pathogenesis of IgG4-related diseases.

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“…IgG4-RD with pleural effusion (5-14) has been previously described. Although Choi et al (12) reported a case of IgG4-RRD that presented with massive pleural effusion as the only pulmonary manifestation, IgG4-RRD more commonly has other types of pulmonary involvement (15).…”

Section: Discussionmentioning

confidence: 99%

IgG4-related Pleuritis with Elevated Adenosine Deaminase in Pleural Effusion

et al. 2018

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An 81-year-old man was admitted with bilateral pleural effusion. A clinical examination showed lymphocytic pleura effusion and elevated serum IgG4 levels, so that IgG4-related disease was suggested, whereas tuberculous pleurisy was suspected because of high adenosine deaminase (ADA) levels in the pleural effusion. A surgical pleural biopsy revealed that there were large numbers of IgG4-positive cells and IgG4/IgG positive cell ratio exceeded 40% in several sites. Accordingly, we diagnosed IgG4-related pleuritis and treated with the patient with glucocorticoid therapy. The ADA levels in pleural effusion can increase in IgG4-related pleuritis, and it is therefore important to perform a pleural biopsy.

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Peripheral CD4+ T cells showing a Th2 phenotype in a patient with Mikulicz's disease associated with lymphadenopathy and pleural effusion

Cited by 52 publications

References 19 publications

Interleukin-21 contributes to germinal centre formation and immunoglobulin G4 production in IgG4-related dacryoadenitis and sialoadenitis, so-called Mikulicz's disease

Interleukin-21 contributes to germinal centre formation and immunoglobulin G4 production in IgG4-related dacryoadenitis and sialoadenitis, so-called Mikulicz's disease

Role of Th2 Cells in IgG4-Related Lacrimal Gland Enlargement

IgG4-related Pleuritis with Elevated Adenosine Deaminase in Pleural Effusion

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