title: CD4+CD28nullT Cells are related to previous cytomegalovirus infection but not to accelerated atherosclerosis in ANCA-associated vasculitis.
abstract: Previous studies have suggested an increased risk for cardiovascular events in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). We analyzed the presence of atherosclerotic damage in patients with AAV in relation to the presence of CD4+CD28nullT cells and antibodies against cytomegalovirus (CMV) and human Heat-Shock Protein 60 (hHSP60). In this cross-sectional study, patients with inactive AAV were compared with healthy controls (HC). Carotid intima-media thickness (IMT) and aortic pulse-wave velocity (PWV) were measured. In addition, CD4+CD28nullT cells, anti-CMV, and anti-hHSP60 levels were determined. Forty patients with AAV were included. Patients' spouses were recruited as HC (N = 38). CD4+CD28nullT cells are present in patients with AAV in a higher percentage (median 3.1, range 0.01-85) than in HC (0.28, 0-36, P < 0.0001). No significant difference in IMT (mm) between patients and controls was detected (mean 0.77 ± standard deviation 0.15 and 0.73 ± 0.11, respectively, P = 0.20). PWV standardized for MAP was increased in AAV patients (9.80 ± 2.50 m/s, compared to 8.72 ± 1.68 in HC, P = 0.04). There was a strong association between a previous CMV infection and the presence and percentage of CD4+CD28nullT cells (0.33 vs 13.8, P < 0.001). There was no relationship between CD4+CD28nullT cells and/or a previous CMV infection and IMT or PWV. There was no relation between anti-hHSP60 and CD4+CD28nullT cells. Increased PWV values suggest atherosclerotic damage in patients with AAV. Plaque size, as determined by IMT, did not differ. CD4+CD28nullT cells are increased in AAV and related to the previous CMV infection.
authors.affiliation: Department of Clinical and Experimental Immunology, University Hospital Maastricht, Maastricht, The Netherlands. m.slot1@vumc.nl.|Department of Internal Medicine, VU Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. m.slot1@vumc.nl.
authors.forename: Marjan C
authors.identifier: http://orcid.org/0000-0002-9487-4758
authors.initials: MC
authors.lastname: Slot
authors.affiliation: Department of Vascular Medicine, University Hospital Maastricht, Maastricht, The Netherlands.
authors.forename: Abraham A
authors.initials: AA
authors.lastname: Kroon
authors.affiliation: Department of Clinical and Experimental Immunology, University Hospital Maastricht, Maastricht, The Netherlands.
authors.forename: Jan G M C
authors.initials: JGMC
authors.lastname: Damoiseaux
authors.affiliation: Department of Clinical and Experimental Immunology, University Hospital Maastricht, Maastricht, The Netherlands.
authors.forename: Ruud
authors.initials: R
authors.lastname: Theunissen
authors.affiliation: Department of Vascular Medicine, University Hospital Maastricht, Maastricht, The Netherlands.
authors.forename: Alfons J H M
authors.initials: AJHM
authors.lastname: Houben
authors.affiliation: Department of Vascular Medicine, University Hospital Maastricht, Maastricht, The Netherlands.
authors.forename: Peter W
authors.initials: PW
authors.lastname: de Leeuw
authors.affiliation: Department of Clinical and Experimental Immunology, University Hospital Maastricht, Maastricht, The Netherlands.
authors.forename: Jan Willem Cohen
authors.initials: JWC
authors.lastname: Tervaert
mesh_terms: D000328:Adult; D000368:Aged; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000276:immunology* / Q000473:pathology; D050197:Atherosclerosis / Q000150:complications / Q000276:immunology* / Q000473:pathology; D018106:CD28 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes; D059168:Carotid Intima-Media Thickness; D003430:Cross-Sectional Studies; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000150:complications / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D018106:CD28 Antigens
keywords: ANCA; Atherosclerosis; CD4+CD28 T cells; Cytomegalovirus; Intima-media thickness; Vasculitis