[Retroperitoneal fibrosis: development of a biomarker profile for diagnosis and therapy monitoring]

Abstract

Introduction: Retroperitoneal fibrosis (RPF) is a rare chronic inflammatory disease which is characterized by fibrotic tissue in the retroperitoneal space. There have only been a few studies on serum markers of this disease. The main goal of the current investigation was to identify biological markers which are increased in the serum of patients suffering from RPF and which may correlate with the extent of fibrosis.

Material and methods: The serum of 42 patients with primary and yet untreated retroperitoneal fibrosis was examined for biomarkers known to be specific for fibrotic diseases and compared to a control group. In addition, patients were stratified according to the extent and volume of the retroperitoneal mass using cross-sectional imaging. To estimate the discriminatory power of the evaluated biomarkers, receiver operating characteristic (ROC) curves were created.

Results: Independent of the extent of fibrosis, calprotectin, fibrinogen, osteopontin, matrix metallopeptidase 9 (MMP-9), tenascin C and TIMP metallopeptidase inhibitor 1 (TIMP-1) were significantly increased (p<0.01) in patients suffering from RPF compared to the control group. Connective tissue growth factor (CTGF) was significantly elevated (p<0.01) in patients with high RPF burden only but monocyte chemoattractant protein 1 (MCP-1) and heart-type fatty acid binding protein (H-FABP) showed no increase in serum levels. The discriminatory power of these parameters was ranked by the ROC analysis which demonstrated an area under the curve (AUC) >0.87 for MMP-9, TIMP-1, osteopontin, tenascin C, asymmetric dimethylarginine (ADMA), fibrinogen and calprotectin and an AUC <0.64 for MMP-2, CTGF, H-FABP and MCP-1.

Conclusion: Several biomarkers of fibrogenesis were significantly elevated in patients suffering from RPF as compared to a control group. These biomarker candidates will be further evaluated for their potential to allow a differentiation between other diseases or if they could be used for disease monitoring.