Clinical studies and biomarkers in SSc

Aligning with the CCISS cohort we have set up a research line that aims to identify biomarkers that improve patient prognostication and contribute to better understanding of these heterogeneity in SSc. Here, we have a focus on SSc-specific autoantibodies, and other variables that become available in clinical practice like nailfoldcapillaroscopy and electrocardiography.

SSc is a severe, but heterogeneous autoimmune disease characterized by the presence of SSc-specific anti-nuclear antibodies. Most SSc patients are either anti-topoisomerase 1 antibody (ATA) or anti-centromere antibody (ACA) positive. These autoantibodies are mutually exclusive and associate with distinct clinical phenotypes, e.g. ATA-positive SSc patients have high risk to develop severe skin involvement and interstitial lung disease, whereas ACA-positive disease is associated with limited skin involvement and gastro-intestinal symptoms. Despite this clear clinical association between autoantibody subtype and clinical phenotype, the role of these autoantibodies to disease pathogenesis has not been established.

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SSc is a severe, but heterogeneous autoimmune disease characterized by the presence of SSc-specific anti-nuclear antibodies. Most SSc patients are either anti-topoisomerase 1 antibody (ATA) or anti-centromere antibody (ACA) positive. These autoantibodies are mutually exclusive and associate with distinct clinical phenotypes, e.g. ATA-positive SSc patients have high risk to develop severe skin involvement and interstitial lung disease, whereas ACA-positive disease is associated with limited skin involvement and gastro-intestinal symptoms. Despite this clear clinical association between autoantibody subtype and clinical phenotype, the role of these autoantibodies to disease pathogenesis has not been established.

Within this research theme we focus, from a clinical perspective, on the association between autoantibody responses and clinical disease manifestations.

We have evaluated ATA IgG, IgM and IgA isotypes in association to disease progression and show that expression of ATA IgM can predict disease progression in the next year.

Following this study we have also performed in-depth evaluation of ACA responses showing that higher ACA IgG level increase the risk of development of SSc.

Currently, we focus on autoantibody isotypes and expression in preclinical / very early SSc, and aim to expand our research line to other disease specific antibodies.

Projects

Themes for innovation/societal outreach

Key publictaions

Our team members

  • Dr. J.K. de Vries-Bouwstra, Rheumatologist, group leader
  • Dr. C.M. Fehres, Postdoctoral researcher
  • Dr. H.U. Scherer, rheumatologist
  • Prof. dr R.E.M. Toesl, Immunologist, head of the Lab on expirmatal rheuamtology LUMC
  • Drs. S.I.E. Liem, Phd-student
  • Drs. S. Ahmed, Phd-student
  • Dr. J. Ciaffi, Rheumatologist, PhD candidate