T-cell expression of CD91 - a marker of unresponsiveness to anti-TNF therapy in rheumatoid arthritis.
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.
Department of Clinical Immunology, University Hospital, Umeå, Sweden. catharina.eriksson@vll.se
Catharina
C
Eriksson
Solbritt
S
Rantapää-Dahlqvist
Karl-Gösta
KG
Sundqvist
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D015703:Antigens, CD / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology*; D051928:CD47 Antigen / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D037282:Calreticulin / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D000069285:Infliximab; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D019700:Thrombospondin 1 / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018501:Antirheumatic Agents; D051928:CD47 Antigen; D037282:Calreticulin; C475476:LRP1 protein, human; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D019700:Thrombospondin 1; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab