CD4+CD28– T-cell expansions in ANCA-associated vasculitis and association with arterial stiffness: baseline data from a randomised controlled trial

Abstract Background Cardiovascular risk is increased in the anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV). CD4+CD28– T cells are expanded in patients with AAV who are seropositive for cytomegalovirus (CMV), and are associated with increased mortality. CMV seropositivity in other conditions is associated with arterial stiffness, a marker of cardiovascular risk. We assessed whether CD4+CD28– T cells in CMV seropositive patients with AAV are associated with arterial stiffness and whether treatment with valaciclovir reduces this cell population. Methods In this open-label phase 2 trial, patients were randomised (1:1) by computer to valaciclovir (8 g daily) or no additional treatment for 6 months. Primary outcome was proportion of patients with CMV reactivation. Arterial stiffness (carotid to femoral pulse wave velocity [PWV]) was measured and peripheral blood CD4+CD28– T cells analysed by flow cytometry at baseline and 6 months. CD4+CD28– T-cell interferon γ (IFNγ) secretion was stimulated with CMV lysate. Data are presented as median (IQR). Between-group differences were tested by Mann-Whitney U test and correlations by Spearman's rank. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT01633476. Findings Baseline data are presented from the first 28 patients enrolled, with 6 months' follow-up completed in five treatment and six control patients. More CD4+CD28– than CD4+CD28+ T cells expressed T-bet (83·5% [47·5–89·9] vs 12·9 [4·7–22·2], p