Abstract
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.
Highlights
Pernicious anemia (PA) is an haematological disorder characterized by immunological and gastric pathologies [1, 2]
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
PA is an autoimmune disease consisting of gastric atrophy, macrocytic anemia, and reduction of parietal cells producing the intrinsic factor which is essential for vitamin B12 absorption
Summary
Pernicious anemia (PA) is an haematological disorder characterized by immunological and gastric pathologies [1, 2]. PA is an autoimmune disease consisting of gastric atrophy, macrocytic anemia, and reduction of parietal cells producing the intrinsic factor which is essential for vitamin B12 absorption. The autoreactive process of PA proceeds during decades up to a severe state associated with a lack of vitamin B12 starting from a mild chronic autoimmune body gastritis (AIG). PA is usually characterized by anemia of the megaloblastic type and gastric atrophy which can be anticipated by neuropathies. The presence in PA of autoantibodies against intrinsic factor (secreted by the gastric parietal cells), and the coexistence in PA patients of other autoimmune disorders (e.g. autoimmune thyroiditis) support the immunopathological autoimmune bases of PA and AIG [4]. PA and AIG patients have documented both gastric mucosal infiltration of activated CD4+ T cells, macrophages and atrophy of the gastric corpus [5]
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