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AB0202 Galectin-9 is a Robust Biomarker for Disease Activity in Juvenile Dermatomyositis and Acts as a T Cell Activator
  1. F. Bellutti Enders1,2,
  2. J. Wienke2,
  3. W. de Jager2,
  4. L. Wedderburn3,
  5. K. Nistala3,
  6. C. Pilkington3,
  7. B. Prakken2,
  8. A. van Royen-Kerkhof2,
  9. F. van Wijk2
  1. 1Pediatrics, Centre Hospitalier Universitaire Vaudois, University hospital, Lausanne, Switzerland
  2. 2Pediatric immunology, Laboratory of translational immunology, UMC Utrecht, Utrecht, Netherlands
  3. 3Pediatric rheumatology, UCL Institute of Child Health, London, United Kingdom

Abstract

Background Juvenile dermatomyositis (JDM) is a rare, but severe chronic systemic autoimmune disease in children, characterized by muscle weakness and a typical skin rash. Clinical evaluation of disease activity remains challenging. Recently, we identified a protein that highly correlates with disease activity in a Dutch JDM cohort: galectin-9 (gal-9). The immunobiological role of gal-9 in autoimmune diseases is still controversial. On the one hand it is known for its immunosuppressive effects by inducing apoptosis in T-helper (Th) 1 and Th17 cells and activating regulatory T cells, on the other hand it has been implicated in T cell activation and Th1 skewing.

Objectives To validate the potential of gal-9 as a biomarker in JDM and investigate its immunobiological effects on T cell skewing and activation.

Methods Gal-9 was measured in patient's serum of an independent JDM cohort by multiplex immunoassay. For functional experiments, naive CD4 T cells were isolated and stimulated with different concentrations of gal-9, plus anti-CD3 and antigen presenting cells. To test specificity, a gal-9 blocking agent (TIM-3 fusion protein) as well as a control from the galectin family (galectin-8) were included. Flow cytometric analysis of proliferation and T cell activation markers was performed on day 3 and 5 of culture. Cytokines TNFα, IFNγ, IL-13, IL-17 and IL-10 were measured in the culture supernatants of days 3, 5 and 7 by multiplex immunoassay.

Results Measurement of gal-9 in serum confirmed its high discriminative value for active disease versus remission (P=.0001; AUC 0.894; OR 9.17) even under medication, as well as a strong correlation with the clinical disease activity scores CMAS and Physician's Global VAS.

On a functional level, the presence of gal-9 induced a slight but significant increase in naive CD4 T cell proliferation after 3 days of culture. The T cell activation markers CD25, CD69 and TIM-3 showed the same pattern. Gal-9 also increased production of IFNγ, TNFα and IL-10, mainly at day 7. These effects were not seen in the control conditions.

Conclusions We confirmed the potential use of a very robust biomarker, galectin-9, that highly correlates with disease activity in juvenile dermatomyositis. Introduction of this biomarker into clinical practice will help to personalize treatment. Functionally, we found that gal-9 is a T cell activator, causing increased proliferation, cytokine production and expression of T cell activation markers. The high levels of circulating gal-9 in JDM patients may therefore contribute to the immunopathogenesis of JDM.

References

  1. Bellutti Enders et al. Correlation of CXCL10, TNFRII, and Galectin-9 With Disease Activity in Juvenile Dermatomyositis. Arthritis Rheumatol. 2014 Aug;66(8):2281-9.

Disclosure of Interest None declared

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