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Targeting Costimulatory Pathways in Systemic Sclerosis.

Gonçalo Boleto1,2, Yannick Allanore1,2, Jérôme Avouac1,2

  • 1Université Paris Descartes, Sorbonne Paris Cité, INSERM U1016, Institut Cochin, CNRS UMR8104, Paris, France.

Frontiers in Immunology
|January 9, 2019
PubMed
Summary
This summary is machine-generated.

Targeting T-cell costimulatory pathways shows promise for treating systemic sclerosis (SSc). Blocking these pathways, like with abatacept, may reduce fibrosis and inflammation in SSc patients.

Keywords:
adaptive immunitycostimulatory pathwaysfibrosisinflammationsystemic sclerosis

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Area of Science:

  • Immunology
  • Rheumatology
  • Dermatology

Background:

  • Systemic sclerosis (SSc) is an autoimmune T-cell disease marked by fibrosis.
  • T-cell costimulatory pathways are crucial for immune responses and may drive SSc pathogenesis.
  • Key molecules like CD28, CTLA-4, ICOS, and OX40L are overexpressed in SSc patients.

Purpose of the Study:

  • To investigate the role of T-cell costimulatory pathways in SSc.
  • To evaluate the therapeutic potential of blocking these pathways in SSc.

Main Methods:

  • Review of pre-clinical models and clinical studies involving T-cell costimulation blockade.
  • Analysis of molecular targets such as CD28/CTLA-4, ICOS-B7RP1, CD70-CD27, CD40-CD154, and OX40-OX40L.
  • Examination of abatacept (CTLA-4-Ig) and OX40L blockade effects.

Main Results:

  • Pre-clinical SSc models showed that abatacept prevented/reversed fibrosis and improved organ involvement.
  • OX40L blockade demonstrated anti-fibrotic effects by reducing inflammation and fibroblast activation.
  • Preliminary clinical data suggest abatacept's efficacy in joint and skin manifestations of SSc.

Conclusions:

  • T-cell costimulatory pathways are viable therapeutic targets for SSc.
  • Targeted blockade offers a potentially safer alternative to broad immunosuppression for SSc treatment.
  • Ongoing clinical trials, like the ASSET trial, will further assess abatacept's efficacy in SSc.