Increased expression of CD40 ligand (CD154) on CD4+ T cells as a marker of disease activity in rheumatoid arthritis

• Published in: Annals of the rheumatic diseases Vol. 59; no. 3; pp. 190 - 195
• Main Authors: Berner, Beate, Wolf, Gabriele, Hummel, Klaus M, Müller, Gerhard A, Reuss-Borst, Monika A
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and European League Against Rheumatism 01.03.2000; BMJ; BMJ Publishing Group LTD
• Subjects: Adult; Aged; Antigens; Antigens, CD - blood; Arthritis, Rheumatoid - immunology; Biological and medical sciences; Biomarkers - blood; CD4+ T cells; CD4-Positive T-Lymphocytes - immunology; CD40 Ligand; Cell growth; Chronic illnesses; Cloning; Dendritic cells; Diseases of the osteoarticular system; Extended Report; Female; Flow Cytometry; Fluorescent Antibody Technique, Direct; Humans; Hypotheses; Immunity, Cellular; Immunoglobulins; Inflammatory joint diseases; Ligands; Lymphocyte Activation - immunology; Lymphocytes; Male; Medical sciences; Membrane Glycoproteins - blood; Middle Aged; Patients; Prognosis; Rheumatoid arthritis; Human; Immunopathology; Flow cytometry; Immune response; Pathogenesis; Diseases of the osteoarticular system; Evolutivity; Biological marker; Autoimmune disease; Inflammatory joint disease; Cellular immunity; Chronic; Rheumatoid arthritis; T-Lymphocyte
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/ard.59.3.190

OBJECTIVES The interaction between the activation induced surface glycoprotein CD40L (ligand) (CD154) on CD4+ T cells and its receptor CD40, which is expressed on various cell types, plays a crucial part in numerous cell mediated and humoral immune reactions that may be of pathogenetic importance in rheumatoid arthritis (RA). To further evaluate the pathogenetic role of CD40L in RA, expression of CD40L and various other T cell activation antigens as well as costimulatory molecules was investigated on CD4+ T cells in RA by flow cytometry. METHODS Two colour flow cytometry was used to determine the percentage of CD4+ T cells expressing CD40L, CD69, CD25, HLA-DR, CD39, CD27 and CD28 in peripheral blood (PB) of 62 RA patients in comparison to 20 healthy controls (HC). Disease activity was assessed by clinical, laboratory and radiological examination. Status of clinical remission of RA was evaluated according to the ACR preliminary criteria for complete clinical remission of RA. RESULTS CD40L was expressed on > 10% of CD4+ T cells in 29% of RA patients thus defining a CD40Lhigh+ patient group. Disease activity as estimated by C reactive protein, rheumatoid factor and status of clinical remission of disease (p = 0.049) was higher in this subgroup than in the RA CD40Llow+ group. Expression of CD69, CD25, and HLA-DR was significantly increased in both RA patient groups in comparison with HC. However, the percentage of CD39+ CD4+ T cells was increased only in the RA CD40Lhigh+ subgroup (versus HC p = 0.019, versus RA CD40Llow+ p = 0.044). Furthermore, expression of CD40L and CD39 on CD4+ T cells correlated positively as estimated by Spearman rank correlation (p < 0.001). The percentage of CD4+ T cells lacking the costimulatory molecules CD27 (p = 0.002) and CD28 (p = 0.026) was increased in RA CD40Llow+ patients in comparison with HC. CONCLUSIONS These data suggest that increased expression of CD40L on CD4+ T cells in RA indicates prolonged and increased activation of CD4+ T lymphocytes and is associated with active disease and possibly an unfavourable prognosis. Whether this phenotypically defined RA CD40Lhigh+ subgroup will preferentially respond to an anti-CD40L antibody treatment remains to be elucidated.