Systemic Sclerosis: Chemokine CXCL4 as a Biomarker of Progression and Phenotype

Prof. Dr. T.R.D.J. Radstake, MD, PhD Staff Rheumatologist / head translational Immunology Department of Rheumatology & Clinical Immunology EULAR Center of Excellence Director, UMC Utrecht Infection and Immunity FOCIS Center of Excellence University Medical Center Utrecht, The Netherlands MedicalResearch.com Interview with:
Prof. Dr. T.R.D.J. Radstake, MD, PhD
Staff Rheumatologist / head translational Immunology
Department of Rheumatology & Clinical Immunology EULAR Center of Excellence
Director, UMC Utrecht Infection and Immunity FOCIS Center of Excellence
University Medical Center Utrecht, The Netherlands

MedicalResearch.com: What are the main findings of the study?

Prof. Radstake: We observed that the chemokine CXCL4 is highly produced by so-called plasmacytoid dendritic cells in systemic sclerosis (Ssc). CXCL4 is associated with the progression and clinical phenotype of Ssc and thus provides a tool for clinicians to identify those patients in need for aggressive therapy and on the other hand, avoid unnecessary side-effects for those who have mild disease. Moreover, the identified roles for CXCL4 in SSc sparks our knowledge on the pathogenic pathways at hand in this terrible conditions. Now, we and other groups will have to further unravel the precise roles for CXCL4 in SSc and possibly other fibrotic and immune mediated conditions that cover the spectrum of medicine.
MedicalResearch.com: Were any of the findings unexpected?

Prof. Radstake: The role of plasmacytoid dendritic cells was already suggested by their production of various inflammatory mediators such as type I Interferon which has been shown to play a role in this condition. That CXCL4 is made in large quantities is completely new. This suggests an important role for pDC other than the expected production if type I IFNs and one that need to be unravelled further.

MedicalResearch.com: What should clinicians and patients take away from your report?

Prof. Radstake: The clinical relevance of this work is pretty high as there is no current effective therapy available for Ssc. Also, there are no biomakers who are able to predict which patient will have severe disease or those who will not. This is utterly important since therapy that is available as kind of last resort for these patients eg. Cyclophosphamide or autologous stem cell transplantation has a high rate of mortality and/or morbidity. Not lastly, the role of CXCL4 we show in the paper provides more insights into the possible pathogenesis of disease. We are now following up onto these observations were we focus onto a better understanding of the precise roles of CXCL4 in the diverse pathological hallmarks of Scleroderma but also to develop CXCL4 as a candidate for future therapeutic targeting.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Prof. Radstake: I believe we should further focus on the precise role of CXCL4 in the pathological circuitry in Ssc which is complex. We now only revealed a tip of the veil. Furthermore, we should focus on CXCL4 as a potential therapeutic target for this condition as well as other medical conditions typified by fibrosis and/or chronic inflammation

Citation:

Proteome-wide Analysis and CXCL4 as a Biomarker in Systemic Sclerosis

Lenny van Bon, M.D., Alsya J. Affandi, M.Sc., Jasper Broen, M.D., Ph.D., Romy B. Christmann, M.D., Ph.D., Renoud J. Marijnissen, Ph.D., Lukasz Stawski, M.Sc., Giuseppina A. Farina, M.D., Ph.D., Giuseppina Stifano, M.D., Allison L. Mathes, Ph.D., Marta Cossu, M.D., Michael York, M.D., Cindy Collins, M.A., Mark Wenink, M.D., Richard Huijbens, M.Sc., Roger Hesselstrand, M.D., Ph.D., Tore Saxne, M.D., Ph.D., Mike DiMarzio, M.Sc., Dirk Wuttge, M.D., Ph.D., Sandeep K. Agarwal, M.D., Ph.D., John D. Reveille, M.D., Ph.D., Shervin Assassi, M.D., Maureen Mayes, M.D., M.P.H., Yanhui Deng, Ph.D., Joost P.H. Drenth, M.D., Ph.D., Jacqueline de Graaf, M.D., Ph.D., Martin den Heijer, M.D., Ph.D., Cees G.M. Kallenberg, M.D., Ph.D., Marc Bijl, M.D., Ph.D., Arnoud Loof, M.Sc., Wim B. van den Berg, Ph.D., Leo A.B. Joosten, Ph.D., Vanessa Smith, M.D., Ph.D., Filip de Keyser, M.D., Ph.D., Rafaella Scorza, M.D., Ph.D., Claudio Lunardi, M.D., Ph.D., Piet L.C.M. van Riel, M.D., Ph.D., Madelon Vonk, M.D., Ph.D., Waander van Heerde, Ph.D., Stephan Meller, M.D., Bernhard Homey, M.D., Lorenzo Beretta, M.D., Ph.D., Mark Roest, Ph.D., Maria Trojanowska, Ph.D., Robert Lafyatis, M.D., and Timothy R.D.J. Radstake, M.D., Ph.D.

December 18, 2013DOI: 10.1056/NEJMoa1114576