Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.

CXCL4, a Novel Marker for Systemic Sclerosis That Clearly Correlates with the Clinical Hallmarks and Pathological Events.

Radstake3,  Timothy Ruben, van Bon2,  Lenny, Broen2,  Jasper, Beatriz-Christmann1,  Romy, Affandi1,  Alsya, Vonk2,  Madelon, York1,  Mike

Boston Medical Center
Radboud University Nijmegen Medical Center
Radboud University Nijmegen Medical Center/Boston Medical Center, Nijmegen, The Netherlands
University Hospital Groninge
University Hospital Groningen
University Hospital Houston, TX
University Hospital Lund, Sweden


Despite recent advances in our understanding of systemic sclerosis (SSc) many patients still suffer from progressive disease leading to severe complications and premature death. Currently predictors for disease phenotype and prognosis are lacking.


We exploited proteome-wide analysis (SELDI-TOF) of secreted proteome from plasmacytoid dendritic cells (pDCs) from clinically well-defined groups of SSc patients (n = 214) to study the differential expression of proteins between SSc subsets. We confirmed the presence of the most predominant protein CXCL4 by ELISA in the supernatant and plasma of SSc patients in comparison with healthy individuals (n=129) and other autoimmune (SLE, n = 109), auto-inflammatory (AS, n = 93) and fibrosing (liver fibrosis, n = 93) clinical conditions. Using SSc phenotypic data including the presence of autoantibodies, skin- and lung fibrosis and pulmonary arterial hypertension (PAH) we examined the potential correlation between these clinical hallmarks and circulating CXCL4 levels. Finally, we studied the direct effects of CXCL4 on skin fibroblasts and HUVEC by investigating COMP expression and secretion of endothelin-1, respectively.


Circulating pDCs were found at higher frequencies in SSc patients but did not spontaneously produce higher levels of IFNa compared to controls. Proteome-wide analysis of SSc pDC supernatants revealed the chemokine CXCL4 as the most abundant protein detected, seen predominantly in patients having early diffuse disease. Validation using ELISA confirmed this observation and also showed that circulating CXCL4 levels were significantly higher in SSc patients compared to controls and other conditions such as SLE, AS and liver fibrosis. CXCL4 levels were higher in diffuse SSc compared with limited SSc but showed by far the highest levels in those patients having early diffuse SSc. CXCL4 levels correlated well with the extent of skin fibrosis and the presence of lung fibrosis and PAH. These correlations could be explained by the ability of CXCL4 to induce myofibroblast transformation of skin fibroblasts and the secretion of endothelin-1 by human endothelial cells (HUVEC).


The anti-angiogenic chemokine CXCL4 is highly expressed in SSc patients and correlates well with the clinical hallmarks of SSc skin- and lung fibrosis and PAH and therefore provides a novel biomarker for SSc phenotype but also other fibrosing diseases.

To cite this abstract, please use the following information:
Radstake, Timothy Ruben, van Bon, Lenny, Broen, Jasper, Beatriz-Christmann, Romy, Affandi, Alsya, Vonk, Madelon, et al; CXCL4, a Novel Marker for Systemic Sclerosis That Clearly Correlates with the Clinical Hallmarks and Pathological Events. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1210
DOI: 10.1002/art.28976

Abstract Supplement

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