Elevated IL-19 Serum Levels in Patients With Pernicious Anemia and Autoimmune Gastritis

Bella, Chiara Della; Antico, Antonio; Panozzo, M.P.; Capitani, Nagaja; Benagiano, Marisa; Petrone, Luisa; Azzurri, Annalisa; Pratesi, Sara; D’Elios, Sofia; Cianchi, Fabio; Ortiz-Princz, Diana; Bizzaro, Nicola; D’Elios, Mario Milco

doi:10.3389/fimmu.2022.887256

Cited by 8 publications

(3 citation statements)

References 30 publications

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“…Gastric specimens from eight AIG patients (having no other autoimmune disease) and four HCs were used as source of LPMCs. Specifically, LPMCs were isolated by the dithiothreitol- ethylenediaminetetraacetic acid (DTT-EDTA)-collagenase sequence ( 18 , 19 ). To investigate the proliferative response to gastric H + /K + -ATPase, purified as reported ( 12 ), LPMCs were labeled with carboxyfluorescein succinimidyl ester (CFSE) (CellTrace CFSE dye, Invitrogen, USA) following manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

Gastric Th17 Cells Specific for H+/K+-ATPase and Serum IL-17 Signature in Gastric Autoimmunity

Bella

Antico²,

Panozzo³

et al. 2022

Front. Immunol.

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Human gastric autoimmunity [autoimmune gastritis (AIG)] is characterized by inflammation of the gastric mucosa and parietal cell loss. The gastric parietal cell proton pump H+/K+-adenosine triphosphatase (H+/K+-ATPase) is the major autoantigen in AIG. Our work aimed to investigate the gastric H+/K+-ATPase-specific T helper 17 (Th17) responses in AIG and serum interleukin (IL)-17 cytokine subfamily in AIG patients, in healthy subjects [healthy controls (HCs)], and in patients with iron deficiency anemia (IDA) without AIG. We analyzed the activation of gastric lamina propria mononuclear cells (LPMCs) by H+/K+-ATPase and the IL-17A and IL-17F cytokine production in eight patients with AIG and four HCs. Furthermore, we compared serum levels of IL-17A, IL-17F, IL-21, IL-17E, IL-22, and IL-23 in 43 AIG patients, in 47 HCs, and in 20 IDA patients without AIG. Gastric LPMCs from all AIG patients, but not those from HCs, were activated by H+/K+-ATPase and were able to proliferate and produce high levels of IL-17A and IL-17F. AIG patients have significantly higher serum IL-17A, IL-17F, IL-21, and IL-17E (393.3 ± 410.02 pg/ml, 394.0 ± 378.03 pg/ml, 300.46 ± 303.45 pg/ml, 34.92 ± 32.56 pg/ml, respectively) than those in HCs (222.99 ± 361.24 pg/ml, 217.49 ± 312.1 pg/ml, 147.43 ± 259.17 pg/ml, 8.69 ± 8.98 pg/ml, respectively) and those in IDA patients without AIG (58.06 ± 107.49 pg/ml, 74.26 ± 178.50 pg/ml, 96.86 ± 177.46 pg/ml, 10.64 ± 17.70 pg/ml, respectively). Altogether, our results indicate that IL-17A and IL-17F are produced in vivo in the stomach of AIG patients following activation with H+/K+-ATPase and that serum IL-17A, IL-17F, IL-21, and IL-17E levels are significantly elevated in AIG patients but not in patients without AIG. These data suggest a Th17 signature in AIG and that IL-17A, IL-17F, IL-21, and IL-17E may represent a relevant tool for AIG management.

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Section: Methodsmentioning

confidence: 99%

Gastric Th17 Cells Specific for H+/K+-ATPase and Serum IL-17 Signature in Gastric Autoimmunity

Bella

Antico²,

Panozzo³

et al. 2022

Front. Immunol.

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“…A study on the cytokine profile of patients with pernicious anemia demonstrated a notable elevation in their serum IL-19 levels compared with healthy controls [19]. Furthermore, an in vitro investigation of gastric lamina propria mononuclear cells derived from patients with pernicious anemia revealed their capacity to produce augmented levels of IL-19.…”

Section: Lymphocytes and Cytokinesmentioning

confidence: 99%

Update in Molecular Aspects and Diagnosis of Autoimmune Gastritis

Iwamuro

Tanaka

Otsuka

2023

CIMB

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Recent studies have advanced our understanding of the pathophysiology of autoimmune gastritis, particularly its molecular aspects. The most noteworthy recent advancement lies in the identification of several candidate genes implicated in the pathogenesis of pernicious anemia through genome-wide association studies. These genes include PTPN22, PNPT1, HLA-DQB1, and IL2RA. Recent studies have also directed attention towards other genes such as ATP4A, ATP4B, AIRE, SLC26A7, SLC26A9, and BACH2 polymorphism. In-depth investigations have been conducted on lymphocytes and cytokines, including T helper 17 cells, interleukin (IL)-17A, IL-17E, IL-17F, IL-21, IL-19, tumor necrosis factor-α, IL-15, transforming growth factor-β1, IL-13, and diminished levels of IL-27. Animal studies have explored the involvement of roseolovirus and H. pylori in relation to the onset of the disease and the process of carcinogenesis, respectively. Recent studies have comprehensively examined the involvement of autoantibodies, serum pepsinogen, and esophagogastroduodenoscopy in the diagnosis of autoimmune gastritis. The current focus lies on individuals demonstrating atypical presentations of the disease, including those diagnosed in childhood, those yielding negative results for autoantibodies, and those lacking the typical endoscopic characteristics of mucosal atrophy. Here, we discuss the recent developments in this field, focusing on genetic predisposition, epigenetic modifications, lymphocytes, cytokines, oxidative stress, infectious agents, proteins, microRNAs, autoantibodies, serum pepsinogen, gastrin, esophagogastroduodenoscopy and microscopic findings, and the risk of gastric neoplasm.

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“…However, there are no clues on the pathogenic process mediated by Helicobacter pylori specific T helper 17 lymphocytes in human gastric intestinal metaplasia and gastric dysplasia. Inflammatory mediators (such as cytokines) which in situ originate in the stomach may diffuse into the blood and then be detected [ 38 ]. Serum cytokine levels of gastric premalignant patients somehow mirror the inflammatory milieu , which is ongoing in the gastric mucosa, suggesting that measurement of serum IL-17A might be useful for monitoring the mucosa inflammation of Helicobacter pylori -infected individuals.…”

Section: Introductionmentioning

confidence: 99%

Increased IL-17A Serum Levels and Gastric Th17 Cells in Helicobacter pylori-Infected Patients with Gastric Premalignant Lesions

Bella

D’Elios

Coletta

et al. 2023

Cancers

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Background: Helicobacter pylori infection is characterized by an inflammatory infiltrate that might be an important antecedent of gastric cancer. The purpose of this study was to evaluate whether interleukin (IL)-17 inflammation is elicited by gastric T cells in Helicobacter pylori patients with gastric intestinal metaplasia and dysplasia (IM/DYS). We also investigated the serum IL-17A levels in Helicobacter pylori patients with gastric intestinal metaplasia and dysplasia, and patients with Helicobacter pylori non-atrophic gastritis (NAG). Methods: the IL-17 cytokine profile of gastric T cells was investigated in six patients with IM/DYS and Helicobacter pylori infection. Serum IL-17A levels were measured in 45 Helicobacter pylori-infected IM/DYS patients, 45 Helicobacter pylori-infected patients without IM/DYS and in 45 healthy controls (HC). Results: gastric T cells from all IM/DYS patients with Helicobacter pylori were able to proliferate in response to Helicobacter pylori and to produce IL-17A. The Luminex analysis revealed that IL-17A levels were significantly increased in Helicobacter pylori IM/DYS patients compared to healthy controls and to Helicobacter pylori gastritis patients without IM/DYS (452.34 ± 369.13 pg/mL, 246.82 ± 156.06 pg/mL, 169.26 ± 73.82 pg/mL, respectively; p < 0.01, p < 0.05). Conclusions: the results obtained indicate that Helicobacter pylori is able to drive gastric IL-17 inflammation in IM/DYS Helicobacter pylori-infected patients, and that IL-17A serum levels are significantly increased in Helicobacter pylori-infected patients with IM/DYS.

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Elevated IL-19 Serum Levels in Patients With Pernicious Anemia and Autoimmune Gastritis

Cited by 8 publications

References 30 publications

Gastric Th17 Cells Specific for H+/K+-ATPase and Serum IL-17 Signature in Gastric Autoimmunity

Gastric Th17 Cells Specific for H+/K+-ATPase and Serum IL-17 Signature in Gastric Autoimmunity

Update in Molecular Aspects and Diagnosis of Autoimmune Gastritis

Increased IL-17A Serum Levels and Gastric Th17 Cells in Helicobacter pylori-Infected Patients with Gastric Premalignant Lesions

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