Volume 8 Supplement 1

5th European Workshop on Immune-Mediated Inflammatory Diseases

Open Access

Variants of PBEF predispose to systemic sclerosis and pulmonary arterial hypertension development

  • JCA Broen1,
  • P Gourh2,
  • M C Vonk1,
  • L Beretta3,
  • F Niederer4,
  • B Rueda5,
  • L Geurts-van Bon1,
  • C Brouwer1,
  • R Hesselstrand6,
  • A Herrick7,
  • J Worthington7,
  • N Hunzelman8,
  • C Denton9,
  • C Fonseca9,
  • G Riemekasten10,
  • H Kiener11,
  • R Scorza3,
  • C P Simeon12,
  • V Fonollosa12,
  • P Carreira13,
  • N Ortego-Centeno14,
  • M A Gonzalez-Gay15,
  • P Airò16,
  • MJH Coenen17,
  • M Mayes2,
  • D Kyburz4,
  • F C Arnett2,
  • J Martin5 and
  • TRDJ Radstake1
Contributed equally
Journal of Translational Medicine20108(Suppl 1):P46


Published: 25 November 2010


Pre B-cell colony-enhancing factor (PBEF) is intricately involved in inflammation and fibrosis, functional polymorphisms of PBEF have been previously shown to influence PBEF expression and pulmonary damage. Systemic sclerosis (SSc) is a disease in which inflammation, fibrosis and pulmonary deterioration are prominent hallmarks. Therefore we here investigate the role of the PBEF -1001T>G and PBEF -1543C>T polymorphisms in the genetic predisposition to systemic sclerosis (SSc) susceptibility and pulmonary involvement.

Patients and methods

We genotyped DNA from 2737 SSc patients and 1913 matched healthy controls, both from 8 different ethnic populations. Genotyping was performed using custom Taqman 5´allelic discrimination assays. In addition, PBEF serum expression levels were measured by ELISA and correlated with genotypes.


In two separate populations and in a meta-analysis, the combined PBEF -1543CC -1001TT genotype, hence carrying no minor alleles, was found associated with SSc susceptibility (P=0.009 OR 1.20 (95% CI 1.05-1.37). In addition, these subjects showed an increased decline in forced vital capacity (FVC) over 15 years follow-up (P=0.02) (HR 1.64, 95%CI: 1.02-2.64) and a higher PBEF serum concentration (P<0.01), compared to carriers of minor alleles. On the other hand, patients with genotype PBEF -1001TT were at lower risk for PAH development within 15 years of disease onset compared to the carriers with genotypes PBEF-1001GG and PBEF-1001TG (P<0.001) (HR 3.29, 95%CI: 1.52-7.12).


Our data identify PBEF as a novel candidate gene that influences SSc susceptibility, pulmonary function and the development of PAH.


Authors’ Affiliations

Dept. of Rheumatology, Radboud University Nijmegen Medical Center
Division of Rheumatology and Clinical Immunogenetics, Dept. of Internal Medicine, University of Texas Health Science Center at Houston (UTHSC-H)
Referral Center for Systemic Autoimmune Diseases, University of Milan
University Hospital Zurich Div. of Rheumatology Zurich
Instituto de Parasitología y Biomedicina, CSIC
Dept. of Rheumatology, Lund University Hospital
Rheumatic Diseases Centre, University of Manchester, Salford Royal NHS Foundation Trust
Dept. of Dermatology, University of Cologne
Centre for Rheumatology, Royal Free and University College Medical School
Dept.of Rheumatology and Clinical Immunology, Charité University Hospital and German Rheumatism Research Centre, a Leibniz institute
Dept. of Internal Medicine, division of Rheumatology, University of Vienna
Servicio de Medicina Interna, Hospital Vall d’Hebron
Servicio de Reumatologia, Hospital 12 de Octubre
Servicio de Medicina Interna, Hospital Clinico Universitario
Servicio de Reumatologia, Hospital Marques de Valdecillas
Servizio di Reumatologia ed Immunologia Clinica
Dept. of Human Genetics, Radboud University Nijmegen Medical Center


© Broen et al; licensee BioMed Central Ltd. 2010

This article is published under license to BioMed Central Ltd.