Intrinsic factor recognition promotes T helper 17/T helper 1 autoimmune gastric inflammation in patients with pernicious anemia
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Arianna Troilo1,*, Alessia Grassi1,*, Luisa Petrone2, Fabio Cianchi3, Marisa Benagiano1, Chiara Della Bella1, Nagaja Capitani4, Jacopo Bitetti1, Sofia D’Elios5, Simona Tapinassi1, Annalisa Azzurri6, Heba Alnwaisri1, Jacopo Romagnoli7, Nicola Bizzaro8, Mathijs Bergman9, Cosima Tatiana Baldari4 and Mario Milco D’Elios1
1 Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
2 Endocrinology Unit, Careggi Hospital, Florence, Italy
3 Department of Surgery, University of Florence, Florence, Italy
4 Department of Life Sciences, University of Siena, Siena, Italy
5 Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
6 Toscana Centro Hospital, Firenze-Prato, Italy
7 Surgery Unit, Rome Catholic University, Italy
8 San Antonio Hospital, Tolmezzo, Italy
9 Amsterdam Institute for Molecules, Medicines and Systems, Vrije University, Amsterdam, The Netherlands
* These authors contributed equally to this work
|Mario Milco D’Elios,||email:||firstname.lastname@example.org|
Keywords: intrinsic factor; interferon-gamma; interleukin-17; pernicious anemia; atrophic gastritis
Abbreviations: AIG: autoimmune gastritis; ATPase: H+,K+-adenosine triphosphatase; IF: intrinsic factor; Hp-CG: type B chronic gastritis without atrophy; PA: pernicious anemia
Received: January 17, 2019 Accepted: April 03, 2019 Published: April 23, 2019
The intrinsic factor is the major humoral autoantigen in pernicious anemia/autoimmune gastritis. Although many studies have examined the autoantibody response to intrinsic factor and H+,K+-ATPase, no information is available on possible pathogenic mechanisms mediated by intrinsic factor - specific gastric T cells. Aim of this study was to investigate intrinsic factor-specific T cells in the gastric mucosa of pernicious anemia patients and define their functional properties. For the first time we provide evidence that gastric mucosa of pernicious anemia patients harbour a high proportion (20%) of autoreactive activated CD4+ T-cell clones that specifically recognize intrinsic factor. Most of these clones (94%) showed a T helper 17 or T helper 1 profile. All intrinsic factor-specific clones produced tumor necrosis factor-α, interleukin-21 and provided substantial help for B-cell immunoglobulin production. Most mucosa-derived intrinsic factor-specific T-cell clones expressed cytotoxicity against target cells. Our results indicate that activation of intrinsic factor-specific T helper 17 and T helper 1 T cells in the gastric mucosa represent a key effector mechanism in pernicious anemia suggesting that the T helper 17/T helper 1 pathway may represent a novel target for the prevention and treatment of the disease.
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