Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Systemic Sclerosis Organ Involvement Is Associated with Increased Adipokine Expression
Neumann1, Elena, Frommer1, Klaus, Vasile2, Massimiliano, Schmeiser1, Tim, Distler3, Oliver, Gay3, Steffen, Riccieri2, Valeria
Justus-Liebig-University of Giessen, Internal Medicine and Rheumatology. Kerckhoff-Klinik, Bad Nauheim, Germany
Cattedra di Reumatologia, Dip Clinica e Terapia Medica, Sapienza Università di Roma, Roma, Italy
Ctr Exp Rheum, Univ Hosp Zurich/Zurich Ctr Integr Hum Physiol (ZIHP), Zurich, Switzerland
Internal Medicine/Pneumology, University of Giessen, Gießen, Germany
Internal Medicine/Gastroenterology, University of Giessen, Gießen, Germany
Systemic sclerosis (SSc) is a connective tissue disorder characterized by progressive fibrosis of the skin and remodeling of the microvasculature. Increased extracellular matrix deposition also affects most internal organs including the gastrointestinal (GI) tract and lungs. Lung fibrosis represents the most common cause of death in SSc. We recently showed that severe fibrosis, increased expression of profibrotic cytokines and numbers of inflammatory cells are important hallmarks in the gastric wall (GW) of SSc patients. Adipokines such as adiponectin, visfatin/PBEF or resistin are immunomodulatory cytokine-like mediators. The present study analyzed whether adipokines are present in SSc-associated inflammation.
Gastric biopsy samples obtained during esophagogastroscopy (corpus, esophagus, antrum) of 5 SSc patients and 2 healthy controls; lung tissues from patients with IPF, EAA/NSIP, controls as well as skin biopsy samples (2 SSc; 2 controls) were obtained. In bronchoalveolar lavages (BAL) of healthy controls (9), patients with SSc (22), IPF (6), and EAA/NSIP (4) adiopokines were measured (ELISA). Adiponectin, visfatin and resistin immunohistochemistry and double stainings with CD45 (LCA), CD3 (T cells), CD20 (mature B cells), CD68 (macrophages), vimentin (fibroblasts), CD31 (endothelial cells) were performed. Affymetrix analysis was performed using skin fibroblasts stimulated with adiponectin.
Expression of adipokines in fibrotic skin, fibrotic lung tissue and the GI-tract of SSc was increased as compared to controls. In the GW, adipokines were localized at sites of inflammation in the mucosal layer without fibrosis in this area. Strongest expression showed adiponectin and visfatin. Adipokines were expressed by fibroblasts, inflammatory cells (CD45) and perivascular. In fibrotic lung tissue increased amounts of adipokines were detectable. Adipokine levels were increased in the BAL of fibrotic lungs when compared to controls (2.5fold) and to idopathic pulmonary fibrosis (1.7fold). Affymetrix array results showed a reduced expression of matrix components and an upregulation of matrix-degrading enzymes (MMPs).
The data show that in SSc patients adipokines are increased at sites of fibrosis in skin and lung. In contrast, adipokines are expressed in the GW at site of inflammation without fibrosis. Further analysis of the role of adipokines in fibrosis and inflammation may help to understand the pathophysiological mechanisms in SSc. Especially the role of adipokines with anti-fibrotic potential are of distinct interest for future investigations.
To cite this abstract, please use the following information:
Neumann, Elena, Frommer, Klaus, Vasile, Massimiliano, Schmeiser, Tim, Distler, Oliver, Gay, Steffen, et al; Systemic Sclerosis Organ Involvement Is Associated with Increased Adipokine Expression [abstract]. Arthritis Rheum 2009;60 Suppl 10 :47