Abatacept mechanism of action: concordance with its clinical profile

Reumatol Clin. 2012 Mar-Apr;8(2):78-83. doi: 10.1016/j.reuma.2011.08.002. Epub 2011 Nov 21.

Abstract

The double and simultaneous molecular interaction between antigen-presentig cells (APC) and T lymphocytes is essential for the optimal activation of the immunological response and requires the participation of two membrane receptor groups. Abatacept is a fusion protein that selectively modulates one of these two ways, by binding to CD80 and CD86 receptors on APC. In this way, the drug inhibits T cell activation, selectively blocking the specific interaction of CD80/CD86 receptors to CD28 and, therefore, inhibiting T cell proliferation and B cell immunological response. This pharmacological action results in the normalization of inflammatory mediators in rheumatoid arthritis patients and in a safe and efficacious clinical response. Abatacept in combination with methotrexate prevents the progression of joint damage and improves physical function in rheumatoid arthritis patients.

Publication types

  • Review

MeSH terms

  • Abatacept
  • Animals
  • Antigen Presentation / drug effects*
  • Antigen-Presenting Cells / drug effects*
  • Antigen-Presenting Cells / immunology
  • Antirheumatic Agents / administration & dosage
  • Antirheumatic Agents / metabolism
  • Antirheumatic Agents / pharmacology*
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / immunology
  • B-Lymphocytes / immunology
  • B7-1 Antigen / immunology
  • B7-1 Antigen / metabolism
  • B7-2 Antigen / immunology
  • B7-2 Antigen / metabolism
  • Binding, Competitive
  • CD28 Antigens / immunology
  • CD28 Antigens / metabolism
  • CTLA-4 Antigen / chemistry
  • CTLA-4 Antigen / physiology
  • Clinical Trials as Topic
  • Drug Evaluation, Preclinical
  • Humans
  • Immunoconjugates / administration & dosage
  • Immunoconjugates / metabolism
  • Immunoconjugates / pharmacology*
  • Immunoconjugates / therapeutic use
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / therapeutic use
  • Lymphocyte Activation
  • Methotrexate / administration & dosage
  • Methotrexate / therapeutic use
  • Mice
  • Models, Immunological
  • T-Cell Antigen Receptor Specificity
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology

Substances

  • Antirheumatic Agents
  • B7-1 Antigen
  • B7-2 Antigen
  • CD28 Antigens
  • CD86 protein, human
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Immunoconjugates
  • Immunosuppressive Agents
  • Abatacept
  • Methotrexate