OBJECTIVE: Coronary artery disease (CAD) is the leading cause of excess deaths in rheumatoid arthritis (RA). However, identification of features denoting patients with a risk of developing CAD is lacking. The composition of circulating peripheral blood mononuclear cell (PBMC) subsets in RA patients differs markedly from that in healthy controls with regard to the extent of T cell activation, with clonal expansion and differentiation to effector memory status, and presence of inflammatory monocytes. In this study, we sought to evaluate whether elevations in these PBMC subpopulations in RA patients could denote those with an increased risk of subclinical CAD, as determined by the presence of coronary artery calcification (CAC). METHODS: The study cohort comprised 72 patients with RA who underwent cardiac computed tomography to assess CAC. PBMC subsets were determined by multiparameter flow cytometry. Multivariable logistic regression was used to determine the associations between PBMC subpopulations and the presence of CAC. RESULTS: Among the 72 patients with RA, 33% had CAC and exhibited significant increases in the levels of circulating CD4 T cell subsets denoting activation and differentiation to the effector memory phenotypes. Analogous increases in the levels of CD8 T cell subsets, as well as in the CD14(high)CD16+ intermediate monocyte subset, were also present in these patients, as compared to those without CAC. The increases in the CD4 and CD8 T cell subsets were highly intercorrelated, whereas the increases in CD14(high)CD16+ monocytes were independent of elevations in the CD4 T cell subsets. After adjustments for relevant confounders, the levels of CD4+CD56+CD57+ T cells and CD14(high)CD16+ monocytes remained associated with the presence of CAC. CONCLUSION: These findings indicate that PBMC subsets are markers for the presence of CAC and suggest that mechanisms of atherogenesis in RA may operate in part through the elevations in these subsets, raising further questions about the mechanisms underlying the presence of such alterations in cell composition in patients with RA and the potential for shared etiologic pathways between RA and cardiovascular disease.
OBJECTIVE:Coronary artery disease (CAD) is the leading cause of excess deaths in rheumatoid arthritis (RA). However, identification of features denoting patients with a risk of developing CAD is lacking. The composition of circulating peripheral blood mononuclear cell (PBMC) subsets in RApatients differs markedly from that in healthy controls with regard to the extent of T cell activation, with clonal expansion and differentiation to effector memory status, and presence of inflammatory monocytes. In this study, we sought to evaluate whether elevations in these PBMC subpopulations in RApatients could denote those with an increased risk of subclinical CAD, as determined by the presence of coronary artery calcification (CAC). METHODS: The study cohort comprised 72 patients with RA who underwent cardiac computed tomography to assess CAC. PBMC subsets were determined by multiparameter flow cytometry. Multivariable logistic regression was used to determine the associations between PBMC subpopulations and the presence of CAC. RESULTS: Among the 72 patients with RA, 33% had CAC and exhibited significant increases in the levels of circulating CD4 T cell subsets denoting activation and differentiation to the effector memory phenotypes. Analogous increases in the levels of CD8 T cell subsets, as well as in the CD14(high)CD16+ intermediate monocyte subset, were also present in these patients, as compared to those without CAC. The increases in the CD4 and CD8 T cell subsets were highly intercorrelated, whereas the increases in CD14(high)CD16+ monocytes were independent of elevations in the CD4 T cell subsets. After adjustments for relevant confounders, the levels of CD4+CD56+CD57+ T cells and CD14(high)CD16+ monocytes remained associated with the presence of CAC. CONCLUSION: These findings indicate that PBMC subsets are markers for the presence of CAC and suggest that mechanisms of atherogenesis in RA may operate in part through the elevations in these subsets, raising further questions about the mechanisms underlying the presence of such alterations in cell composition in patients with RA and the potential for shared etiologic pathways between RA and cardiovascular disease.
Authors: Robert Winchester; Margrit Wiesendanger; Will O'Brien; Hui-Zhu Zhang; Mathew S Maurer; Linda D Gillam; Allan Schwartz; Charles Marboe; Allan S Stewart Journal: J Immunol Date: 2011-06-15 Impact factor: 5.422
Authors: Nels C Olson; Margaret F Doyle; Nancy Swords Jenny; Sally A Huber; Bruce M Psaty; Richard A Kronmal; Russell P Tracy Journal: PLoS One Date: 2013-08-23 Impact factor: 3.240
Authors: Andreas E R Fasth; Omri Snir; Anna A T Johansson; Birgitta Nordmark; Afsar Rahbar; Erik Af Klint; Niklas K Björkström; Ann-Kristin Ulfgren; Ronald F van Vollenhoven; Vivianne Malmström; Christina Trollmo Journal: Arthritis Res Ther Date: 2007 Impact factor: 5.156
Authors: Jon T Giles; Mary Chester M Wasko; Cecilia P Chung; Moyses Szklo; Roger S Blumenthal; Amy Kao; Sabahat Bokhari; Afshin Zartoshti; C Michael Stein; Joan M Bathon Journal: Arthritis Rheumatol Date: 2019-08-01 Impact factor: 10.995
Authors: Iván Ferraz-Amaro; Robert Winchester; Peter K Gregersen; Richard J Reynolds; Mary Chester Wasko; Anette Oeser; Cecilia P Chung; C Michael Stein; Jon T Giles; Joan M Bathon Journal: Arthritis Rheumatol Date: 2017-03 Impact factor: 10.995
Authors: Laura Geraldino-Pardilla; Jon T Giles; Jeremy Sokolove; Afshin Zartoshti; William H Robinson; Matthew Budoff; Robert Detrano; Sabahat Bokhari; Joan M Bathon Journal: Arthritis Care Res (Hoboken) Date: 2017-07-10 Impact factor: 4.794
Authors: Dragana Dragoljevic; Michael J Kraakman; Prabhakara R Nagareddy; Devi Ngo; Waled Shihata; Helene L Kammoun; Alexandra Whillas; Man Kit Sam Lee; Annas Al-Sharea; Gerard Pernes; Michelle C Flynn; Graeme I Lancaster; Mark A Febbraio; Jaye Chin-Dusting; Beatriz Y Hanaoka; Ian P Wicks; Andrew J Murphy Journal: Eur Heart J Date: 2018-06-14 Impact factor: 29.983