Rheumatology

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Increased production of soluble CTLA-4 in patients with spondylarthropathies correlates with disease activity
Arthritis Research & Therapy, 07/08/09

Toussirot E et al. – Spondylarthropathies (SpA) patients exhibit high levels of circulating soluble form of CTLA-4 (sCTLA-4) that may result from an alternative splicing of CTLA-4 transcripts; may influence immune activation and regulation in SpA.

• Main objectives of this study were to:
  • Evaluate the circulating levels of sCTLA-4 as a marker of immune dysregulation in SpA
  • Study the intracellular CTLA-4 and levels of CTLA-4 transcript expression in peripheral blood lymphocytes (PBL)
• Sera from 165 pts were evaluated for sCTLA-4 measurements
• Results were compared to those from 71 RA pts and 88 healthy subjects
• In 32 pts with SpA, 22 pts with RA and 15 healthy controls, intracellular CTLA-4 expression in:
  • CD4+ T cells
  • CD8+ T cells
  • Activated (HLA-DR+Foxp3-) CD4+ T cells
  • CD4+ regulatory (CD25+Foxp3+) T cells and in
  • CD3 negative cells
    were analyzed by flow cytometry
• Expression of the full length and spliced form of CTLA-4 transcripts in PBL were analyzed by qRT-PCR

• High levels of sCTLA-4 were found in the SpA group vs RA group and healthy controls
• Soluble CTLA-4 serum levels strongly correlated with clinical index of disease activity BASDAI and CRP levels
• In contrast to RA pts, SpA pts did not exhibit changes in intracellular CTLA-4 expression in the different PBL subsets tested
• Finally, the SpA group showed a preferential expression of the spliced CTLA-4 mRNA in PBL

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