The Experts below are selected from a list of 603 Experts worldwide ranked by ideXlab platform
Chernkang Perng - One of the best experts on this subject based on the ideXlab platform.
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clinicopathology of immunoglobulin g4 related chronic sclerosing sialadenitis a single center study
Otolaryngology-Head and Neck Surgery, 2016Co-Authors: Dunhao Chang, Yuchen Wang, Chinhsuan Lin, Chernkang PerngAbstract:ObjectivesTo investigate the clinicopathologic characteristics of patients with immunoglobulin G4–related chronic sclerosing sialadenitis (IgG4-RCSS), a recently recognized disease.Study DesignCase series with chart review and pathology study.SettingsTertiary care hospital.Subjects and MethodsWe evaluated chronic sialadenitis specimens obtained over 11 years using pathologic examination and IgG4 immunohistochemistry staining. The specimens were assigned a revised diagnosis of IgG4-RCSS or chronic sialadenitis not otherwise specified, and clinicopathologic data from each group were compared.ResultsOf the 84 patients, 21 were diagnosed with IgG4-RCSS and 63 with chronic sialadenitis not otherwise specified. IgG4-RCSS patients were older (68.2 ± 13.9 vs 54.2 ± 15.8 years, P = .001), predominantly male (85.7% vs 61.9%, P = .036), and more likely to present with painless swelling (75% vs 44.3%, P = .001) and bilateral involvement (52.4% vs 6.3%, P < .001). Ratio of IgG4-positive plasma cells to IgG-positive pl...
Dunhao Chang - One of the best experts on this subject based on the ideXlab platform.
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clinicopathology of immunoglobulin g4 related chronic sclerosing sialadenitis a single center study
Otolaryngology-Head and Neck Surgery, 2016Co-Authors: Dunhao Chang, Yuchen Wang, Chinhsuan Lin, Chernkang PerngAbstract:ObjectivesTo investigate the clinicopathologic characteristics of patients with immunoglobulin G4–related chronic sclerosing sialadenitis (IgG4-RCSS), a recently recognized disease.Study DesignCase series with chart review and pathology study.SettingsTertiary care hospital.Subjects and MethodsWe evaluated chronic sialadenitis specimens obtained over 11 years using pathologic examination and IgG4 immunohistochemistry staining. The specimens were assigned a revised diagnosis of IgG4-RCSS or chronic sialadenitis not otherwise specified, and clinicopathologic data from each group were compared.ResultsOf the 84 patients, 21 were diagnosed with IgG4-RCSS and 63 with chronic sialadenitis not otherwise specified. IgG4-RCSS patients were older (68.2 ± 13.9 vs 54.2 ± 15.8 years, P = .001), predominantly male (85.7% vs 61.9%, P = .036), and more likely to present with painless swelling (75% vs 44.3%, P = .001) and bilateral involvement (52.4% vs 6.3%, P < .001). Ratio of IgG4-positive plasma cells to IgG-positive pl...
Takayuki Sumida - One of the best experts on this subject based on the ideXlab platform.
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the anergy induction of m3 muscarinic acetylcholine receptor reactive cd4 t cells suppresses experimental sialadenitis like sjogren s syndrome
Arthritis & Rheumatism, 2015Co-Authors: Hiromitsu Asashima, Mana Iizuka, Hiroto Tsuboi, Tomoya Hirota, Yuya Kondo, Isao Matsumoto, Hiroyuki Takahashi, Minoru Matsui, Takayuki SumidaAbstract:Objective Autoreactive CD4+ T cells are involved in the pathogenesis of Sjogren's syndrome (SS). The aim of the present study was to clarify the dominant T cell epitopes of M3 muscarinic acetylcholine receptor (M3R) and to establish a new antigen-specific therapy for SS using an experimental mouse model. Methods Production of cytokines from M3R-reactive CD4+ T cells, after culture with various M3R peptides, was analyzed by enzyme-linked immunosorbent assay. Adoptive cell transfer was performed using splenocytes from M3R−/− mice that were immunized with M3R peptides or phosphate buffered saline plus H37Ra as a control. Rag1−/− mice were inoculated with the splenocytes and examined for the development of sialadenitis. Altered peptide ligands (APLs) of the T cell epitopes, with substitutions in amino acid residues at T cell receptor contact sites, were synthesized, and the ability of the APLs to suppress sialadenitis was evaluated. The mechanisms underlying such effects were assessed. Results CD4+ M3R-reactive T cells produced interleukin-17 (IL-17) and interferon-γ (IFNγ) in response to the N-terminal 1 (N1) and 1st extracellular loop peptides of M3R, and Rag1−/− mice that received N1- and/or 1st peptide–immunized splenocytes developed sialadenitis. Among the designed APLs, N1-APL7 (NS at amino acid 15) significantly suppressed IFNγ production in vitro, and also suppressed sialadenitis in vivo. Levels of early growth response 2 in CD4+ T cells from the cervical lymph nodes of N1-APL7–treated mice were significantly higher than those of control mice, and cell proliferation was reversed by administration of exogenous IL-2. Levels of the anergy-related molecules itchy homolog E3 ubiquitin-protein ligase, Casitas B-lineage lymphoma b, gene related to anergy in lymphocytes, and Deltex-1 were significantly higher in CD4+ T cells cultured with N1-APL7. Conclusion The major T cell epitopes were from the N1 and 1st peptide regions. Moreover, N1-APL7, selected as the antagonistic APL in vitro, also suppressed sialadenitis through the induction of anergy. This is a potentially useful strategy for regulating pathogenic T cell infiltration in SS.
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a crucial role of rorγt in the development of spontaneous sialadenitis like sjogren s syndrome
Journal of Immunology, 2015Co-Authors: Mana Iizuka, Hiroto Tsuboi, Naomi Matsuo, Hiromitsu Asashima, Tomoya Hirota, Yuya Kondo, Yoichiro Iwakura, Satoru Takahashi, Isao Matsumoto, Takayuki SumidaAbstract:The nuclear receptor retinoic acid-related orphan receptor (ROR)γt is required for the generation of Th17 cells, which are involved in various autoimmune diseases, including Sjogren's syndrome (SS). However, the pathological role of RORγt in SS remains to be elucidated. The present study was designed to clarify the role of RORγt in the pathogenesis of sialadenitis-like SS. Histological analysis of RORγt transgenic (Tg) mice was determined, and then Tg mice developed severe spontaneous sialadenitis-like SS. The analysis of infiltrating cells showed that most infiltrating cells were CD4(+) T cells. RORγt-overexpressing CD4(+) T cells induced sialadenitis as a result of transferred CD4(+) T cells from Tg mice into Rag2(-/-) mice. The examination of IL-17-deficient Tg mice indicated that IL-17 was not essential for the development of sialadenitis. The number of CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells was significantly decreased in Tg mice, and CD25 expression and IL-2 stimulated STAT5 activation were inhibited in Treg cells. The inhibitory function of Treg cells of Tg mice was equal to that of wild-type mice in vitro. The abundant Treg cells of Tg mice could suppress the development of sialadenitis, but the reduced Treg cells of Tg mice could not inhibit the induction of sialadenitis in Rag2(-/-) mice transferred with effector cells from Tg mice. These results suggest that both RORγt-overexpressed CD4(+) T cells and reduced Treg cells might contribute to the development of SS-like sialadenitis.
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the role of m3 muscarinic acetylcholine receptor reactive t cells in sjogren s syndrome a critical review
Journal of Autoimmunity, 2014Co-Authors: Takayuki Sumida, Mana Iizuka, Hiroto Tsuboi, Hiromitsu Asashima, Tomoya Hirota, Isao MatsumotoAbstract:CD4+ T cells constitute the majority of infiltrating cells in salivary glands and lachrymal glands of patients with Sjogren's syndrome (SS). The pathophysiology of SS involves T cell recognition of antigens through the T cell antigen receptor, which triggers cytokine production and chronic inflammation. The M3 muscarinic acetylcholine receptor (M3R) molecule is expressed in exocrine glands, such as salivary glands and lachrymal glands, and plays an important role in exocrine secretion. Previous studies indicated the presence of M3R reactive T cells in peripheral blood of 40% of patients with SS and autoantibodies against M3R in sera of 9-100% of the same patients. Thus, M3R is considered a candidate receptor for autoantigen recognition by T and B cells. The relationship between B cell epitopes and the function of anti-M3R antibodies has been reported, suggesting the pathogenic role of anti-M3R antibodies in xerostomia commonly seen in SS patients. We generated new experimental mouse model, M3R-induced sialadenitis (MIS), using Rag1(-/-) mice inoculated with splenocytes from M3R(-/-) mice immunized with M3R synthetic peptides. Mice with MIS developed severe SS-like sialadenitis. Cell transfer experiments using M3R(-/-)xIFNγ(-/-) mice and M3R(-/-)xIL-17(-/-) mice showed that IFNγ and IL-17 are key cytokines in the pathogenesis of sialadenitis. These findings indicate the crucial roles of M3R-reactive Th1 and Th17 cells in autoimmune sialadenitis, and suggest that these cells, in addition to anti-M3R antibodies, are potential targets in new treatments for SS.
Jeongseok Choi - One of the best experts on this subject based on the ideXlab platform.
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salivary gland function after sialendoscopy for treatment of chronic radioiodine induced sialadenitis
Head and Neck-journal for The Sciences and Specialties of The Head and Neck, 2016Co-Authors: Young-mo Kim, Jeongseok Choi, In Young Hyun, Seong Bin Hong, Jaeyoul LimAbstract:Background The purpose of this study was to determine whether sialendoscopy could ameliorate radioactive iodine-induced obstructive sialadenitis and restore the salivary gland dysfunction in recalcitrant radioactive iodine sialadenitis. Methods Ten patients with 15 parotid glands of chronic radioactive iodine sialadenitis who did not respond to medical treatment were enrolled in this prospective study. We assessed subjective symptom scores and evaluated the objective salivary gland functions before and 3 months after sialendoscopy. Results The post-sialendoscopic obstructive symptoms were significantly improved relative to pre-sialendoscopy (p = .009). Xerostomia-related symptom scores post-sialendoscopy did not differ significantly from the pre-sialendoscopy scores. Stimulated salivary flow rate post-sialendoscopy tended to increase relative to pre-sialendoscopy. No pre-sialendoscopic parameters associated with salivary uptake and secretion by salivary gland scintigraphy were significantly improved post-sialendoscopy. Conclusion These results show that sialendoscopy can improve obstructive symptoms; however, it seems to have some limitations for relief of xerostomia and improvement of salivary gland dysfunctions in recalcitrant chronic radioactive iodine sialadenitis. © 2015 Wiley Periodicals, Inc. Head Neck 38: 51–58, 2016
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usefulness of magnetic resonance sialography for the evaluation of radioactive iodine induced sialadenitis
Annals of Surgical Oncology, 2015Co-Authors: Jeongseok ChoiAbstract:Purpose Radioactive iodine (RAI) ablation therapy after thyroidectomy commonly leads to obstructive sialadenitis. Magnetic resonance (MR) sialography is an emerging imaging modality that enables morphological and functional changes to be evaluated. This study was conducted to investigate the usefulness of MR sialography for the evaluation of RAI sialadenitis. In addition, the authors evaluated the correlation of MR sialographic grading with symptom severity using a symptom questionnaire (SQ), and salivary gland (SG) functions as determined by salivary flow rates (SFRs) and salivary scintigraphy (SSG) parameters.
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usefulness of magnetic resonance sialography for the evaluation of radioactive iodine induced sialadenitis
Annals of Surgical Oncology, 2015Co-Authors: Jeongseok Choi, Young-mo Kim, Hyun Gon Lim, Myung Kwan Lim, Ha Young Lee, Jae Yol LimAbstract:Radioactive iodine (RAI) ablation therapy after thyroidectomy commonly leads to obstructive sialadenitis. Magnetic resonance (MR) sialography is an emerging imaging modality that enables morphological and functional changes to be evaluated. This study was conducted to investigate the usefulness of MR sialography for the evaluation of RAI sialadenitis. In addition, the authors evaluated the correlation of MR sialographic grading with symptom severity using a symptom questionnaire (SQ), and salivary gland (SG) functions as determined by salivary flow rates (SFRs) and salivary scintigraphy (SSG) parameters. Eighteen patients with RAI sialadenitis who underwent MR sialography imaging were retrospectively enrolled. Subjective symptom scores were assessed and objective SG functions were evaluated. MR sialographic characteristics were analyzed and correlations between MR sialographic findings and clinicopathologic data, SQ, SFRs, and SSG parameters were investigated. MR sialography demonstrated diagnostic findings of ductal stenosis and sialectasis, non-visualized ducts, and glandular atrophy mainly involving parotid glands. A significant correlation was found between obstructive symptom scores and ductal stenosis and sialectasis grades (both p < 0.05). Degrees of ductal stenosis and sialectasis were significantly correlated with SSG excretory variables [time from stimulation to minimum count (t min) and maximum secretion; all p < 0.05]. Significant linear correlations were found between duct nonvisualization and uptake variables [uptake ratio (UR) and maximum accumulation (MA); both p < 0.05]. Glandular volumes were also significantly correlated with UR and MA (both p < 0.05). MR sialography images are useful for evaluating RAI sialadenitis, and its findings are in accordance with disease severity. An MR sialographic grading system is suggested to describe the severity of obstructive sialadenitis and SG dysfunction.
Isao Matsumoto - One of the best experts on this subject based on the ideXlab platform.
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the anergy induction of m3 muscarinic acetylcholine receptor reactive cd4 t cells suppresses experimental sialadenitis like sjogren s syndrome
Arthritis & Rheumatism, 2015Co-Authors: Hiromitsu Asashima, Mana Iizuka, Hiroto Tsuboi, Tomoya Hirota, Yuya Kondo, Isao Matsumoto, Hiroyuki Takahashi, Minoru Matsui, Takayuki SumidaAbstract:Objective Autoreactive CD4+ T cells are involved in the pathogenesis of Sjogren's syndrome (SS). The aim of the present study was to clarify the dominant T cell epitopes of M3 muscarinic acetylcholine receptor (M3R) and to establish a new antigen-specific therapy for SS using an experimental mouse model. Methods Production of cytokines from M3R-reactive CD4+ T cells, after culture with various M3R peptides, was analyzed by enzyme-linked immunosorbent assay. Adoptive cell transfer was performed using splenocytes from M3R−/− mice that were immunized with M3R peptides or phosphate buffered saline plus H37Ra as a control. Rag1−/− mice were inoculated with the splenocytes and examined for the development of sialadenitis. Altered peptide ligands (APLs) of the T cell epitopes, with substitutions in amino acid residues at T cell receptor contact sites, were synthesized, and the ability of the APLs to suppress sialadenitis was evaluated. The mechanisms underlying such effects were assessed. Results CD4+ M3R-reactive T cells produced interleukin-17 (IL-17) and interferon-γ (IFNγ) in response to the N-terminal 1 (N1) and 1st extracellular loop peptides of M3R, and Rag1−/− mice that received N1- and/or 1st peptide–immunized splenocytes developed sialadenitis. Among the designed APLs, N1-APL7 (NS at amino acid 15) significantly suppressed IFNγ production in vitro, and also suppressed sialadenitis in vivo. Levels of early growth response 2 in CD4+ T cells from the cervical lymph nodes of N1-APL7–treated mice were significantly higher than those of control mice, and cell proliferation was reversed by administration of exogenous IL-2. Levels of the anergy-related molecules itchy homolog E3 ubiquitin-protein ligase, Casitas B-lineage lymphoma b, gene related to anergy in lymphocytes, and Deltex-1 were significantly higher in CD4+ T cells cultured with N1-APL7. Conclusion The major T cell epitopes were from the N1 and 1st peptide regions. Moreover, N1-APL7, selected as the antagonistic APL in vitro, also suppressed sialadenitis through the induction of anergy. This is a potentially useful strategy for regulating pathogenic T cell infiltration in SS.
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a crucial role of rorγt in the development of spontaneous sialadenitis like sjogren s syndrome
Journal of Immunology, 2015Co-Authors: Mana Iizuka, Hiroto Tsuboi, Naomi Matsuo, Hiromitsu Asashima, Tomoya Hirota, Yuya Kondo, Yoichiro Iwakura, Satoru Takahashi, Isao Matsumoto, Takayuki SumidaAbstract:The nuclear receptor retinoic acid-related orphan receptor (ROR)γt is required for the generation of Th17 cells, which are involved in various autoimmune diseases, including Sjogren's syndrome (SS). However, the pathological role of RORγt in SS remains to be elucidated. The present study was designed to clarify the role of RORγt in the pathogenesis of sialadenitis-like SS. Histological analysis of RORγt transgenic (Tg) mice was determined, and then Tg mice developed severe spontaneous sialadenitis-like SS. The analysis of infiltrating cells showed that most infiltrating cells were CD4(+) T cells. RORγt-overexpressing CD4(+) T cells induced sialadenitis as a result of transferred CD4(+) T cells from Tg mice into Rag2(-/-) mice. The examination of IL-17-deficient Tg mice indicated that IL-17 was not essential for the development of sialadenitis. The number of CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells was significantly decreased in Tg mice, and CD25 expression and IL-2 stimulated STAT5 activation were inhibited in Treg cells. The inhibitory function of Treg cells of Tg mice was equal to that of wild-type mice in vitro. The abundant Treg cells of Tg mice could suppress the development of sialadenitis, but the reduced Treg cells of Tg mice could not inhibit the induction of sialadenitis in Rag2(-/-) mice transferred with effector cells from Tg mice. These results suggest that both RORγt-overexpressed CD4(+) T cells and reduced Treg cells might contribute to the development of SS-like sialadenitis.
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the role of m3 muscarinic acetylcholine receptor reactive t cells in sjogren s syndrome a critical review
Journal of Autoimmunity, 2014Co-Authors: Takayuki Sumida, Mana Iizuka, Hiroto Tsuboi, Hiromitsu Asashima, Tomoya Hirota, Isao MatsumotoAbstract:CD4+ T cells constitute the majority of infiltrating cells in salivary glands and lachrymal glands of patients with Sjogren's syndrome (SS). The pathophysiology of SS involves T cell recognition of antigens through the T cell antigen receptor, which triggers cytokine production and chronic inflammation. The M3 muscarinic acetylcholine receptor (M3R) molecule is expressed in exocrine glands, such as salivary glands and lachrymal glands, and plays an important role in exocrine secretion. Previous studies indicated the presence of M3R reactive T cells in peripheral blood of 40% of patients with SS and autoantibodies against M3R in sera of 9-100% of the same patients. Thus, M3R is considered a candidate receptor for autoantigen recognition by T and B cells. The relationship between B cell epitopes and the function of anti-M3R antibodies has been reported, suggesting the pathogenic role of anti-M3R antibodies in xerostomia commonly seen in SS patients. We generated new experimental mouse model, M3R-induced sialadenitis (MIS), using Rag1(-/-) mice inoculated with splenocytes from M3R(-/-) mice immunized with M3R synthetic peptides. Mice with MIS developed severe SS-like sialadenitis. Cell transfer experiments using M3R(-/-)xIFNγ(-/-) mice and M3R(-/-)xIL-17(-/-) mice showed that IFNγ and IL-17 are key cytokines in the pathogenesis of sialadenitis. These findings indicate the crucial roles of M3R-reactive Th1 and Th17 cells in autoimmune sialadenitis, and suggest that these cells, in addition to anti-M3R antibodies, are potential targets in new treatments for SS.