Elena Neumann1, Nina Lepper2, Massimiliano Vasile3, Valeria Riccieri4, Marvin Peters2, Florian Meier2, Marie-Lisa Hülser2, Oliver Distler5, Steffen Gay5, Poornima Mahavadi6, Andreas Günther6, Elke Roeb7, Klaus W Frommer2, Magnus Diller2, Ulf Müller-Ladner2. 1. Dept of Rheumatology and Clinical Immunology, Campus Kerckhoff, Justus-Liebig-University, Giessen, Germany. Electronic address: e.neumann@kerckhoff-klinik.de. 2. Dept of Rheumatology and Clinical Immunology, Campus Kerckhoff, Justus-Liebig-University, Giessen, Germany. 3. Dept of Rheumatology and Clinical Immunology, Campus Kerckhoff, Justus-Liebig-University, Giessen, Germany; Dept Internal Medicine and Medical Specialties, Sapienza University Rome, Rome, Italy. 4. Dept Internal Medicine and Medical Specialties, Sapienza University Rome, Rome, Italy. 5. Div Rheumatology, University Hospital Zurich, Zurich, Switzerland. 6. Med Clinic II, Pneumology, Justus-Liebig-University Giessen, Germany. 7. Med Clinic II, Gastroenterology, Justus-Liebig-University Giessen, Germany.
Abstract
OBJECTIVES: The immunomodulatory properties of adipokines have previously been reported in autoimmune disorders. Less is known about the role of adipokines in systemic sclerosis (SSc). Lung and gastrointestinal tract are frequently involved in SSc; therefore, these organs were analyzed for adipokine expression as well as pulmonary samples of patients suffering from idiopathic pulmonary fibrosis (IPF) as comparison. METHODS: Gastric samples (antrum, corpus) of SSc were analyzed immunohistochemically for adiponectin, resistin and visfatin compared with non-SSc related gastritis. Inflammatory cells were quantified in gastric samples and correlated with adipokine expression. Lung samples of SSc, IPF and healthy controls were also analyzed. Protein levels of lung tissue lysates and bronchoalveolar lavages (BAL) in minor fibrotic stages were measured by ELISA. RESULTS: Lung sections of donor parenchyma showed significantly stronger adiponectin signals as IPF and SSc (donor vs. IPF: p < 0.0001). In SSc and IPF, resistin and visfatin were increased within immune cell infiltrates, but overall no difference in expression for resistin or visfatin compared to controls was observed. In BAL and lung protein lysates of early stages of fibrosis, adiponectin and visfatin were not reduced in IPF and SSc compared to controls. In gastric samples collected by standard endoscopic gastric biopsy, adiponectin was also significantly reduced in SSc- compared to non-SSc gastritis (p = 0.049) while resistin and visfatin were comparable although deeper fibrotic layers were not included in the respective samples. Adiponectin-positive tissues showed higher amounts of CD4+ but not CD8+ T cells. Controls showed no correlation between CD4+ T cells and resistin, whereas SSc showed significantly more CD4+ T cells in resistin-negative tissues. CONCLUSION: Adipokines are expressed in gastric and lung samples of patients with SSc and in lung samples affected by IPF. Prominently, adiponectin levels were reduced in fibrotic SSc gastritic tissue as well as in IPF and SSc lung tissue. Consequently, adiponectin expression seems to be associated with fibrotic progression in the context of SSc and IPF.
OBJECTIVES: The immunomodulatory properties of adipokines have previously been reported in autoimmune disorders. Less is known about the role of adipokines in systemic sclerosis (SSc). Lung and gastrointestinal tract are frequently involved in SSc; therefore, these organs were analyzed for adipokine expression as well as pulmonary samples of patients suffering from idiopathic pulmonary fibrosis (IPF) as comparison. METHODS: Gastric samples (antrum, corpus) of SSc were analyzed immunohistochemically for adiponectin, resistin and visfatin compared with non-SSc related gastritis. Inflammatory cells were quantified in gastric samples and correlated with adipokine expression. Lung samples of SSc, IPF and healthy controls were also analyzed. Protein levels of lung tissue lysates and bronchoalveolar lavages (BAL) in minor fibrotic stages were measured by ELISA. RESULTS: Lung sections of donor parenchyma showed significantly stronger adiponectin signals as IPF and SSc (donor vs. IPF: p < 0.0001). In SSc and IPF, resistin and visfatin were increased within immune cell infiltrates, but overall no difference in expression for resistin or visfatin compared to controls was observed. In BAL and lung protein lysates of early stages of fibrosis, adiponectin and visfatin were not reduced in IPF and SSc compared to controls. In gastric samples collected by standard endoscopic gastric biopsy, adiponectin was also significantly reduced in SSc- compared to non-SSc gastritis (p = 0.049) while resistin and visfatin were comparable although deeper fibrotic layers were not included in the respective samples. Adiponectin-positive tissues showed higher amounts of CD4+ but not CD8+ T cells. Controls showed no correlation between CD4+ T cells and resistin, whereas SSc showed significantly more CD4+ T cells in resistin-negative tissues. CONCLUSION: Adipokines are expressed in gastric and lung samples of patients with SSc and in lung samples affected by IPF. Prominently, adiponectin levels were reduced in fibrotic SSc gastritic tissue as well as in IPF and SSc lung tissue. Consequently, adiponectin expression seems to be associated with fibrotic progression in the context of SSc and IPF.
Authors: Monica M Yang; Lauren C Balmert; Roberta Goncalves Marangoni; Mary Carns; Monique Hinchcliff; Benjamin D Korman; John Varga Journal: Arthritis Care Res (Hoboken) Date: 2021-07-12 Impact factor: 5.178
Authors: Tejaswini Kulkarni; Kaiyu Yuan; Thi K Tran-Nguyen; Young-Il Kim; Joao A de Andrade; Tracy Luckhardt; Vincent G Valentine; Daniel J Kass; Steven R Duncan Journal: PLoS One Date: 2019-10-04 Impact factor: 3.240