K Koskenpato1,2, M Ainola1, B Przybyla1, V-P Kouri1, L Virkki1, J Koskenpato3,4, A Ristimäki4,5, Y T Konttinen1,4,6. 1. a Department of Medicine , University of Helsinki , Helsinki , Finland. 2. b Department of Anatomy , University of Helsinki , Helsinki , Finland. 3. c Department of Gastroenterology , University of Helsinki , Helsinki , Finland. 4. d Helsinki University Central Hospital , Helsinki , Finland. 5. e Department of Pathology , University of Helsinki , Helsinki , Finland. 6. f ORTON Orthopaedic Hospital , ORTON Foundation , Helsinki , Finland.
Abstract
OBJECTIVES: Healthy human labial salivary glands produce epidermal growth factor (EGF). In Sjögren's syndrome (SS), EGF staining is diminished. SS is also associated with chronic autoimmune corpus gastritis. We therefore hypothesized that EGF secretion would be diminished in SS and that this could affect gastric target cells. METHODS: Salivary EGF secretion in SS was compared to that in healthy controls using an enzyme-linked immunosorbent assay (ELISA). EGF receptor (EGFR) immunoreactive cells in the gastric corpus of healthy human subjects were analysed using immunostaining. RESULTS: Salivary secretion of EGF was diminished in SS patients (232.4, range 52.6-618.4, vs. 756.6, range 105.3-1631.6 pg/min, p = 0.002). Proton-pump positive parietal cells were mostly EGFR immunoreactive whereas very few pepsinogen I (PGI)-positive cells were EGFR positive. CONCLUSIONS: As EGF is relatively acid resistant, salivary gland-derived EGF might participate in an exo/endocrine mode of parietal cell maintenance in the gastric corpus. Deficiency of salivary gland-derived EGF in SS patients may cause impairment of gastric parietal cells resulting in exposure of immunogenic cryptic antigens and loss of immunological self-tolerance.
OBJECTIVES: Healthy human labial salivary glands produce epidermal growth factor (EGF). In Sjögren's syndrome (SS), EGF staining is diminished. SS is also associated with chronic autoimmune corpus gastritis. We therefore hypothesized that EGF secretion would be diminished in SS and that this could affect gastric target cells. METHODS: Salivary EGF secretion in SS was compared to that in healthy controls using an enzyme-linked immunosorbent assay (ELISA). EGF receptor (EGFR) immunoreactive cells in the gastric corpus of healthy human subjects were analysed using immunostaining. RESULTS: Salivary secretion of EGF was diminished in SS patients (232.4, range 52.6-618.4, vs. 756.6, range 105.3-1631.6 pg/min, p = 0.002). Proton-pump positive parietal cells were mostly EGFR immunoreactive whereas very few pepsinogen I (PGI)-positive cells were EGFR positive. CONCLUSIONS: As EGF is relatively acid resistant, salivary gland-derived EGF might participate in an exo/endocrine mode of parietal cell maintenance in the gastric corpus. Deficiency of salivary gland-derived EGF in SS patients may cause impairment of gastric parietal cells resulting in exposure of immunogenic cryptic antigens and loss of immunological self-tolerance.
Authors: Iris L A Bodewes; Peter J van der Spek; Leticia G Leon; Annemarie J M Wijkhuijs; Cornelia G van Helden-Meeuwsen; Liselotte Tas; Marco W J Schreurs; Paul L A van Daele; Peter D Katsikis; Marjan A Versnel Journal: Front Immunol Date: 2019-02-26 Impact factor: 7.561
Authors: Antonio Cano-Ortiz; Aurora Laborda-Illanes; Isaac Plaza-Andrades; Alberto Membrillo Del Pozo; Alberto Villarrubia Cuadrado; Marina Rodríguez Calvo de Mora; Isabel Leiva-Gea; Lidia Sanchez-Alcoholado; María Isabel Queipo-Ortuño Journal: Int J Mol Sci Date: 2020-11-19 Impact factor: 5.923