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THU0046 Abatacept Decreases Disease Activity in the Absence of CD4+ T-Cells in the Collagen Induced Arthritis Model
  1. D. Jansen1,
  2. H. el Bannoudi1,
  3. R. Arens2,
  4. K. Habets1,
  5. M. Hameetman1,
  6. T. Huizinga1,
  7. J. Stoop1,
  8. R. Toes1
  1. 1Rheumatology
  2. 2Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands

Abstract

Background Abatacept is a fusion protein of human CTLA-4 and the Fc portion of human IgG1. It is believed to be effective in the treatment of rheumatoid arthritis by blocking the co-stimulation of T-cells via blocking CD28-B7 interaction as CTLA-4 binds to both B7.1 (CD80) and B7.2 (CD86). However, the interaction of CD28 with B7 is crucial for the activation of naïve cells, whereas it is unclear whether the action of already activated CD4+ T-cells, which are readily present in established disease, also depend on this interaction.

Objectives The aim of this study was to determine whether the mode of action of Abatacept depends on its ability to halt T-cell activation in established disease.

Methods Arthritis was induced in thymectomized male DBA/1 mice by immunisation with bovine collagen type II. The mice were subsequently depleted for CD4+ T-cells. Abatacept or control treatment was started when 80% of the mice showed signs of arthritis. Arthritis severity was monitored by clinical scoring of the paws and anti-collagen antibody levels over time were determined by ELISA.

Results Treatment with Abatacept in the absence of CD4+ T-cells resulted in lower disease activity. This was associated with decreasing levels of collagen specific IgG1 and IgG2a antibodies while the antibody levels in control- or CD4+ T-cell-depleted mice increased over time.

Conclusions These results show that Abatacept decreased disease activity in the absence of CD4+ T-cells indicating that the mode of action of Abatacept in established arthritis does not entirely depend on its effects on CD4+ T-cell activation.

Disclosure of Interest None declared

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