Session Title: Rheumatoid Arthritis - Human Etiology and Pathogenesis
Session Type: Abstract Submissions (ACR)
CD4+ T cells which lack CD28 co-expression (CD28null cells) account for less than 2.5% of CD4+ T cells in healthy individuals. These cells are pro-inflammatory, resistant to apoptosis and have cytolytic properties. Increased circulating numbers are found in some RA patients and their presence is associated with extra-articular disease. In unstable angina patients, CD28null cells are independently associated with recurrent cardiac events and are thought to promote atherosclerotic plaque rupture. The aims of the current study were to quantify CD28null cells in RA patients and to investigate the association with RA disease characteristics and subclinical cardiovascular disease.
RA patients with active arthritis, who were not taking a statin, were recruited to a prospective observational study. Clinical and serological evaluation of RA disease characteristics was undertaken including extra-articular involvement, the disease activity 28 score (DAS-28) and the health assessment questionnaire (HAQ). Presence of carotid plaque was evaluated using B-mode doppler ultrasound. Plaque was defined as 2 out of 3: intimal medial thickness>1.5mm, luminal protrusion, increased wall echogenicity.
CD28null cells were quantified using flow cytometry. In brief, fluorescently labelled CD45, CD28 and CD4 antibodies were added to whole blood. Following red cell lysis, flow cytometry was used to measure the proportion of CD45+CD4+ lymphocytes which lacked CD28 expression. Presence of an expanded CD28null cell population was defined as >2.5% of CD45+CD4+ T cells lacking CD28 expression. Descriptive and non-parametric statistics were used to analyse the data.
91 RA patients were included in the study and 68 (74.2%) were female. Median (IQR) age and disease duration was 56(48, 62) and 9(4, 19) years respectively. 64 patients (70.3%) were rheumatoid factor positive and 74 patients (81.3%) were ACPA positive. 1 patient had a history of clinical cardiovascular disease.
Expanded CD28null cell populations were found in 28 patients (30.8%). Presence of CD28 null cells were associated with rheumatoid factor positivity (p=0.02) but not with ACPA positivity. No association was found with age, disease activity, HAQ, biologic use, extra-articular disease or with carotid plaque.
The current study confirms that this abnormal T cell subset is expanded in a significant proportion of RA patients. There was no association between CD28null cells and carotid plaque but these cells may contribute to plaque destabilisation and rupture rather than plaque development. Prospective evaluation of cardiovascular outcomes in this population is underway.
I. N. Bruce,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/numbers-of-circulating-cd4-positive-cd28null-t-cells-are-increased-in-patients-with-rheumatoid-arthritis-and-are-associated-with-rheumatoid-factor-positivity-but-not-subclinical-cardiovascular-disease/