Distinct disease-specific Tfh cell populations in 2 different fibrotic diseases: IgG4-related disease and Kimura disease

Munemura, Ryusuke; Mitsui, Takashi; Murakami, Yasuki; Koga, Risako; Aoyagi, Ryuichi; Kaneko, Naoki; Doi, Akira; Perugino, Cory A.; Della-Torre, Emanuel; Saeki, Takako; Sato, Yasuharu; Yamamoto, Hidetaka; Kiyoshima, Tamotsu; Stone, John H.; Pillai, Shiv; Nakamura, Seiji

doi:10.1016/j.jaci.2022.03.034

Cited by 37 publications

(27 citation statements)

References 45 publications

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“…48 This theory needs validation in studies showing IL-10expressing Tfh cells in ectopic germinal centers within the EoE mucosa, as documented in IgG4-related diseases. 55 Regardless, our findings speak against the idea that IgG4 induction is a univocal consequence of IL-10 expression in the EoE mucosa. No statistical association was in fact apparent between the two variables, and negligible frequencies of IgG4 + cells, with correspondingly low serum sIgG4 levels, were found in ˜50% of specimens harboring substantial numbers of IL-10 + cells.…”

Section: Discussionmentioning

confidence: 53%

Changes in IgG4 and IL-10 expression in adults with eosinophilic esophagitis on a two-food elimination diet

Santonicola

Appanna

Gargano

et al. 2023

Preprint

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Background: Eosinophilic esophagitis (EoE) is increasingly diagnosed in patients with dysphagia and upper gastroenteric symptoms. Elimination diets and/or pharmacologic agents may accomplish temporary remission, but long-term control is challenging. Type-2 immunity to ingested antigens can induce EoE histopathology via non-IgE-dependent mechanisms, possibly involving IgG4 and IL-10 production. To elucidate the contribution of IgG4- and IL-10-producing cells to EoE pathogenesis, we examined their frequencies and association with clinical and histologic endpoints in adult EoE patients given a two-food elimination diet (TFED). Methods: Sixteen patients with EoE were prescribed a TFED. Biopsies collected at baseline and follow-up were used for immunofluorescent detection of IgG4- and IL-10-expressing cells and serum food-specific IgG4 were measured. All variables were correlated with established histologic measures of disease activity. Results: Patients exhibited significant clinical improvement and significant reduction in esophageal eosinophilia and overall histology. A significant decrease in the frequencies of IL-10-expressing cells was also observed, which correlated with histologic changes. In contrast, a concomitant decline in serum and esophageal IgG4, while substantial, did not correlate with IL-10 -cell frequencies or any histologic parameter of EoE activity. Conclusions: The close association of esophageal IL-10 expression with histologic features and their changes after a TFED suggests a critical role of this cytokine in EoE pathogenesis. Conversely, IgG4 serum and mucosal expression, while reflecting the level of exposure to relevant food antigens, is not obviously related to EoE histopathology or IL-10 expression. Studies are needed to characterize IL-10 cellular sources and their functions in EoE progression and treatment response.

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Section: Discussionmentioning

confidence: 53%

Changes in IgG4 and IL-10 expression in adults with eosinophilic esophagitis on a two-food elimination diet

Santonicola

Appanna

Gargano

et al. 2023

Preprint

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“… 15 Involvement of specific T cells has been described in Kimura‘s disease, 24 25 and many differences in comparison to IgG4-related disease. 25 Taken together, there were several overlapping manifestations in that study, but histopathological examination revealed meaningful differences in the types of fibrosis, eosinophils and IgG4-positive cell counts.…”

Section: Discussionmentioning

confidence: 60%

Bilateral swelling of the salivary glands and sicca symptoms: an unusual differential diagnosis—Kimura’s disease, a rare allergic condition with a high IgE serum level—a case report and review of the literature

et al. 2023

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A 68-year-old woman presented with bilateral swelling of the salivary glands, sicca symptoms of eyes and mouth, itching, fatigue and weight gain of about 5 kg in the last 2–3 years. As part of a careful diagnostic work up including lab tests for antinuclear antibodies (ANA), antibodies to extractable nuclear antigens (ENA), anti-neutrophilic cytoplasmatic antiobodies (ANCA), immunoglobulin (Ig)G4, a whole body computed tomography (CT) and a parotid biopsy several rheumatic diseases such as Sjoegren’s syndrome, IgG4-related disease and sarcoidosis were ruled out and, considering a very high titre of IgE, Kimura’s disease was diagnosed. The case and a short review of the literature are presented.

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“…While the predominant source of IgG4 in KD is presumably Th2 cells ( 23 ), it was recently revealed that a subset of profibrotic CD4 + cytotoxic T cells are the major instigators of IgG4-RD ( 24 ). Most recently, while investigating the nature of follicular T (Tfh) cells, researchers found two disease-specific conditions associated with distinct subsets of Tfh cells ( 25 ). It has been suggested that KD represents a process of “allergic fibrosis” that is Th2-driven, whereas IgG4-RD involves a form of “inflammatory fibrosis” orchestrated by cytotoxic T cells ( 25 ).…”

Section: Discussionmentioning

confidence: 99%

“…Most recently, while investigating the nature of follicular T (Tfh) cells, researchers found two disease-specific conditions associated with distinct subsets of Tfh cells ( 25 ). It has been suggested that KD represents a process of “allergic fibrosis” that is Th2-driven, whereas IgG4-RD involves a form of “inflammatory fibrosis” orchestrated by cytotoxic T cells ( 25 ).…”

Section: Discussionmentioning

confidence: 99%

Kimura’s disease: A clinicopathological study of 23 cases

Lee

Chan

2022

Front. Med.

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IntroductionKimura’s disease (KD) is an uncommon lymphoproliferative fibroinflammatory disorder. Patients present with head and neck subcutaneous nodules with or without lymphadenopathy. Peripheral blood eosinophilia and elevated serum immunoglobulin E (IgE) levels are typical. This study was designed to delineate the clinicopathological features, pattern of care, and disease course of 23 Taiwanese patients with KD.MethodsWe retrospectively analyzed the clinical data of 23 consecutive cases (16 male and 7 female; age at diagnosis: 12–77 years) of KD diagnosed at our institution from 2015 to 2020.ResultsThe median time from presentation to diagnosis was 1 month. Twenty-one patients presented with unilateral or bilateral head and neck masses. The remaining two presented with right flank and right arm lesions, respectively. Peripheral blood eosinophilia was observed in nine, and elevated IgE levels were observed in four. All were diagnosed using either excisional or core-needle biopsy. Seven patients underwent fine needle aspiration without a diagnostic yield. Salivary gland and lymph node involvement was observed in three and seven patients, respectively. Most lesions showed tissue eosinophilia (100%) and florid follicular hyperplasia (78.26%). Three cases had histological KD-IgG4-RD overlap and three had comorbid IgG4-RD were recognized. Thirteen patients underwent surgical resection, one received adjuvant therapy, and two received prednisolone monotherapy.ConclusionKD should be considered in patients with subcutaneous masses, eosinophilia, and elevated IgE levels. Biopsy remains the gold standard of diagnosis. Increased recruitment of IgG4+ plasma cells is a common feature. Consideration of IgG4-RD in all KD patients may be prudent.

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Distinct disease-specific Tfh cell populations in 2 different fibrotic diseases: IgG4-related disease and Kimura disease

Cited by 37 publications

References 45 publications

Changes in IgG4 and IL-10 expression in adults with eosinophilic esophagitis on a two-food elimination diet

Changes in IgG4 and IL-10 expression in adults with eosinophilic esophagitis on a two-food elimination diet

Bilateral swelling of the salivary glands and sicca symptoms: an unusual differential diagnosis—Kimura’s disease, a rare allergic condition with a high IgE serum level—a case report and review of the literature

Kimura’s disease: A clinicopathological study of 23 cases

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