Contents lists available at ScienceDirect Cytokine journal homepage: www.elsevier.com/locate/cytokine Adipokine expression in systemic sclerosis lung and gastrointestinal organ involvement Elena Neumann a, ⁎ , Nina Lepper a , Massimiliano Vasile a,b , Valeria Riccieri b , Marvin Peters a , Florian Meier a , Marie-Lisa Hülser a , Oliver Distler c , Steffen Gay c , Poornima Mahavadi d , Andreas Günther d , Elke Roeb e , Klaus W. Frommer a , Magnus Diller a , Ulf Müller-Ladner a a Dept of Rheumatology and Clinical Immunology, Campus Kerckhoff, Justus-Liebig-University, Giessen, Germany b Dept Internal Medicine and Medical Specialties, Sapienza University Rome, Rome, Italy c Div Rheumatology, University Hospital Zurich, Zurich, Switzerland d Med Clinic II, Pneumology, Justus-Liebig-University Giessen, Germany e Med Clinic II, Gastroenterology, Justus-Liebig-University Giessen, Germany ARTICLE INFO Keywords: Systemic sclerosis Idiopathic pulmonary fibrosis Adiponectin Visfatin Resistin 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 pul- monary samples of patients suffering from idiopathic pulmonary fibrosis (IPF) as comparison. Methods: Gastric samples (antrum, corpus) of SSc were analyzed immunohistochemically for adiponectin, re- sistin 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 com- pared 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 com- parable 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. 1. Introduction Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease. Its multifaceted pathophysiology involves an overactive im- mune system with increased matrix deposition in skin and internal organs alongside disturbed angiogenesis and general vasculopathy. SSc can affect the majority of internal organs. SSc patients are classified as diffuse cutaneous SSc (dcSSc) with early, more severe internal organ involvement or as limited cutaneous SSc (lcSSc) with less severe and a later onset of organ involvement [1,2]. The severity of organ involve- ment is the main reason for SSc-related morbidity and mortality. Be- sides the skin as primarily involved organ, gastrointestinal tract (GI), lung and heart are most commonly involved. At least 90% of SSc pa- tients report GI symptoms caused by increasing stiffness and reduced https://doi.org/10.1016/j.cyto.2018.11.013 Received 4 May 2018; Received in revised form 12 October 2018; Accepted 12 November 2018 ⁎ Corresponding author at: Justus-Liebig-University Giessen, Internal Medicine and Rheumatology, Kerckhoff-Klinik GmbH, Benekestr. 2-8, D-61231 Bad Nauheim, Germany. E-mail address: e.neumann@kerckhoff-klinik.de (E. Neumann). Cytokine 117 (2019) 41–49 1043-4666/ © 2019 Elsevier Ltd. All rights reserved. T