Circulating pro-inflammatory CD4posCD28null T cells are independently associated with cardiovascular disease in ESRD patients.
BACKGROUND
Cytomegalovirus seropositivity is associated with an increased risk for cardiovascular disease in end-stage renal disease (ESRD) patients. Circulating pro-inflammatory CD4posCD28null T cells are expanded in cytomegalovirus-seropositive ESRD patients and potentially could mediate atherosclerotic plaque instability and rupture.


METHODS
In this study, we tested the hypothesis that increased numbers of circulating CD4posCD28null T cells may represent a risk factor for cardiovascular disease in ESRD patients. Prospectively collected data from 240 cytomegalovirus-seropositive stable ESRD patients were analysed.


RESULTS
Traditional cardiovascular risk factors (age, smoking, hypercholesterolaemia and diabetes mellitus) and the percentage and absolute number of CD4posCD28null T cells were significantly associated with the presence of atherosclerotic disease, after univariate and multivariate statistical analysis. An ~2-3-fold increase in the prevalence of atherosclerotic disease was noted between patients with the highest and lowest number of CD4posCD28null cells. CD8posCD28null T-cell populations were also significantly expanded in cytomegalovirus-seropositive ESRD patients and closely correlated with the number of CD4posCD28null T cells. However, this cell population was not related to an increased prevalence of cardiovascular disease.


CONCLUSIONS
Cytomegalovirus-seropositive ESRD patients may have substantially increased numbers of circulating pro-inflammatory CD4posCD28null T cells that are independently associated with the presence of atherosclerotic disease. The expansion of these cells may therefore represent a novel non-traditional cardiovascular risk factor for ESRD patients.
Betjes
Michiel G H
MG
Erasmus Medical Center, Department of Internal Medicine, Division of Nephrology, Rotterdam, The Netherlands. M.G.H.Betjes@erasmusmc.nl
de Wit
Elly E A
EE
Weimar
Willem
W
Litjens
Nicolle H R
NH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000209:etiology / Q000276:immunology; D018106:CD28 Antigens / Q000032:analysis*; D015704:CD4 Antigens / Q000032:analysis*; D002318:Cardiovascular Diseases / Q000209:etiology*; D003586:Cytomegalovirus Infections / Q000150:complications; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013601:T-Lymphocytes / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D018106:CD28 Antigens; D015704:CD4 Antigens; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma