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:10.3109/s10165-007-0010-3

Cited by 71 publications

(40 citation statements)

References 15 publications

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“…In our previous studies, we demonstrated that Th2 immune reactions contributed to Mikulicz disease and IgG4-related tubulointerstitial nephritis (23,24,35). The expression profile of cytokines demonstrated in this study suggested that Mikulicz disease was characterized by an intense expression of Th2 and regulatory cytokines (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

“…We previously reported that peripheral CD4ϩ T cells from patients with Mikulicz disease revealed deviation of the Th1/Th2 balance to Th2 and elevated the expression of Th2-type cytokines (23,24). Moreover, recent studies have indicated that peripheral blood CD4ϩ T cells in patients with IgG4-related lacrimal gland enlargement showed a Th2 bias and elevated serum IgE levels (24).…”

Section: Conclusion These Results Suggest That the Pathogenesis Of Mmentioning

confidence: 99%

“…In order to provide a meaningful comparison between different individuals or samples, we calculated the relative amounts of the PCR products of these molecules to the amounts of the PCR products of CD3␦ (for the standardization of T cell mRNA) or the PCR products of ␤-actin (for the standardization of total cellular mRNA) in each sample, as previously described (22,23,35,36). The CD3␦ PCR product levels were used for T cell-specific molecules, such as IL-2, IL-5, IL-12, and IFN␥, while the ␤-actin PCR product levels were used for T cell-nonspecific molecules, such as IL-4, IL-6, IL-10, IL-17, and chemokines, which were produced by a variety of cell types.…”

Section: Methodsmentioning

confidence: 99%

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Th2 and regulatory immune reactions contribute to IgG4 production and the initiation of Mikulicz disease

Tanaka¹,

Moriyama²,

Nakashima³

et al. 2011

Arthritis & Rheumatism

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Objective Mikulicz disease has been considered to be a subtype of Sjögren's syndrome (SS). However, recent studies have suggested that Mikulicz disease is an IgG4‐related disease and is distinguishable from SS. In addition, it has been reported that both interleukin‐4 (IL‐4) and IL‐10 induce IgG4 production and inhibit IgE. This study was undertaken to examine the expression of these cytokines in patients with Mikulicz disease and patients with SS. Methods Labial salivary gland (LSG) sections from 15 patients with Mikulicz disease and 18 patients with SS were examined for subsets of the infiltrating lymphocytes, expression patterns of messenger RNA (mRNA) for cytokines/chemokines, and relationships between the IgG4:IgG ratio and the expression of mRNA for IL‐4 or IL‐10. Results Immunohistochemical analysis showed lymphocyte infiltration of various subsets in the LSGs of SS patients, and the selective infiltration of IgG4‐positive plasma cells and Treg cells in the LSGs of Mikulicz disease patients. The levels of mRNA for both Th1 and Th2 cytokines and chemokines in LSGs from patients with SS were significantly higher than in controls, while the expression of both Th2 and Treg cells was significantly higher in the patients with Mikulicz disease than in controls. Furthermore, the expression of IL‐4 or IL‐10 in the LSGs was correlated with the IgG4:IgG ratio. Conclusion These results suggest that the pathogenesis of Mikulicz disease is different from that of SS. Mikulicz disease is a unique inflammatory disorder characterized by Th2 and regulatory immune reactions that might play key roles in IgG4 production.

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Section: Discussionmentioning

confidence: 99%

Section: Conclusion These Results Suggest That the Pathogenesis Of Mmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Th2 and regulatory immune reactions contribute to IgG4 production and the initiation of Mikulicz disease

Tanaka¹,

Moriyama²,

Nakashima³

et al. 2011

Arthritis & Rheumatism

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217

159

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“…3a, b) [28], and honeycombing in the lower lung field [40]. While IgG4-related respiratory lesions of interstitial pneumonia, nodular lesions, localized ground glass-opacity (GGO), and pleural lesions sometimes occurred without a pancreatic lesion [16,[41][42][43][44][45], a definitive diagnosis of IgG4-related respiratory lesions was difficult in patients with intrathoracic lesions alone, as IgG4-bearing plasma cells have also been observed in other types of lung lesions [46].…”

Section: (Level Of Recommendation: B)mentioning

confidence: 99%

Amendment of the Japanese Consensus Guidelines for Autoimmune Pancreatitis, 2013 II. Extrapancreatic lesions, differential diagnosis

et al. 2014

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“…The immune reaction in SS and MD appeared to be deviations to Th1 and Th2, respectively. Miyake et al (13) analyzed peripheral CD4+ T cells from a patient with MD associated with lymphadenopathy and pleural effusion and demonstrated a Th2-predominant phenotype. In addition, they also analyzed cytokine mRNA expression levels in salivary gland specimens from the patient and the Th2 cytokines, IL-4, IL-5 and IL-10, were elevated.…”

Section: B C D Amentioning

confidence: 99%

A Case of Mikulicz's Disease, IgG4-related Plasmacytic Syndrome, Successfully Treated by Corticosteroid and Mizoribine, Followed by Mizoribine Alone

et al. 2010

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We report a case of Mikulicz's disease, IgG4-related plasmacytic syndrome, successfully treated with corticosteroid and mizoribine, followed by mizoribine alone. A 56-year-old woman experienced persistent bilateral swelling in the eyelids and submandibular region accompanied by lymphadenopathy without pain. The patient was diagnosed as having Mikulicz's disease since her bilateral lacrimal glands showed persistent swelling and biopsy specimens of the submandibular glands and lymph node showed diffuse infiltration of lymphocytes and plasma cells. Symptoms and laboratory data were improved with corticosteroids (30 mg). However, after tapering prednisolone to 5 mg, submandibular swelling developed. Adding mizoribine resulted in clinical improvement. Prednisolone was tapered and finally discontinued. Since the levels of IgG4 in peripheral blood were increased even after corticosteroid therapy and IgG4 was positive in a submandibular gland specimen obtained before the start of corticoid therapy. Thus, this case may be associated with IgG4. The present case is the first case in which mizoribine was effective for Mikulicz's disease and IgG4-related plasmacytic syndrome.

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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 71 publications

References 15 publications

Th2 and regulatory immune reactions contribute to IgG4 production and the initiation of Mikulicz disease

Th2 and regulatory immune reactions contribute to IgG4 production and the initiation of Mikulicz disease

Amendment of the Japanese Consensus Guidelines for Autoimmune Pancreatitis, 2013 II. Extrapancreatic lesions, differential diagnosis

A Case of Mikulicz's Disease, IgG4-related Plasmacytic Syndrome, Successfully Treated by Corticosteroid and Mizoribine, Followed by Mizoribine Alone

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