T-cell expression of CD91 - a marker of unresponsiveness to anti-TNF therapy in rheumatoid arthritis

APMIS. 2010 Nov;118(11):837-45. doi: 10.1111/j.1600-0463.2010.02677.x. Epub 2010 Sep 2.

Abstract

The aim of this study was to investigate the expression of thrombospondin-1 (TSP-1) and its receptors, lipoprotein receptor-related protein/cluster of differentiation (CD)91, calreticulin (CRT), and CD47, on T cells and monocytes from patients with rheumatoid arthritis (RA) treated with anti-tumor necrosis factor (TNF) therapy. The surface expression of CD91 and associated components on CD3- and CD14-positive cells was examined using flow cytometry in 12 patients with established RA before and after beginning therapy and compared with that of 9 healthy controls and 12 patients with early RA treated with conventional therapies. CD3-positive cells from anti-TNF non-responders showed significantly greater expression of CD91 expression than those from responders (p<0.05) after 6 weeks and when all measurements were pooled (p<0.001). CD91 expression on CD3-positive cells from non-responders to other therapies was at the same level as in healthy controls. In contrast, CD14-positive cells showed no differences in CD91 expression between patients and controls or between responders and non-responders to anti-TNF therapy. The expression of TSP-1, CRT, and CD47 showed no differences between responders and non-responders. The results suggest T-lymphocyte expression of CD91 to be a biomarker that signifies unresponsiveness to anti-TNF therapy in patients with RA and may be used to identify potential responders and non-responders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / administration & dosage*
  • Antigens, CD / biosynthesis*
  • Antigens, CD / blood
  • Antigens, CD / immunology
  • Antirheumatic Agents / administration & dosage*
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / immunology*
  • CD47 Antigen / biosynthesis
  • CD47 Antigen / blood
  • CD47 Antigen / immunology
  • Calreticulin / biosynthesis
  • Calreticulin / blood
  • Calreticulin / immunology
  • Female
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Infliximab
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Male
  • Middle Aged
  • Statistics, Nonparametric
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Thrombospondin 1 / biosynthesis
  • Thrombospondin 1 / blood
  • Thrombospondin 1 / immunology
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Antirheumatic Agents
  • CD47 Antigen
  • Calreticulin
  • LRP1 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Thrombospondin 1
  • Tumor Necrosis Factor-alpha
  • Infliximab