TY - JOUR
T1 - CD4+CD28- T lymphocytes contribute to early atherosclerotic damage in rheumatoid arthritis patients
AU - Gerli, Roberto
AU - Schillaci, Giuseppe
AU - Giordano, Andrea
AU - Bocci, Elena Bartoloni
AU - Bistoni, Onelia
AU - Vaudo, Gaetano
AU - Marchesi, Simona
AU - Pirro, Matteo
AU - Ragni, Federica
AU - Shoenfeld, Yehuda
AU - Mannarino, Elmo
PY - 2004/6/8
Y1 - 2004/6/8
N2 - Background - Peripheral blood expansion of an unusual CD4+ T-cell subset lacking surface CD28 has been suggested to predispose rheumatoid arthritis (RA) patients to develop more aggressive disease. However, the potential association between CD4+CD28null T cells and early atherosclerotic changes in RA has never been investigated. Methods and Results - The number of circulating CD4+CD28null cells was evaluated in 87 RA and 33 control subjects who also underwent evaluation of carotid artery intima-media thickness (IMT) and endothelial function via flow-mediated vasodilation (FMV). Patients had higher IMT and lower FMV compared with control subjects. The frequency of CD4+CD28null cells was significantly higher in patients than in control subjects. Twenty patients with persistent expansion of circulating CD4+CD28null cells had more marked increase of carotid artery IMT and stronger decrease of brachial artery FMV. Blockade of tumor necrosis factor-α led to a partial reappearance of the CD28 molecule on the CD4+ cell surface. Conclusions - Circulating CD4+CD28null lymphocytes are increased in RA. Patients with persistent CD4+CD28null cell expansion show preclinical atherosclerotic changes, including arterial endothelial dysfunction and carotid artery wall thickening, more significantly than patients without expansion. These findings suggest a contribution of this cell subset in atheroma development in RA. Moreover, the demonstration that tumor necrosis factor-α blockade is able to reverse, at least in part, the CD28 deficiency on the CD4+ cell surface may be of interest for possible innovative therapeutic strategies in cardiovascular diseases.
AB - Background - Peripheral blood expansion of an unusual CD4+ T-cell subset lacking surface CD28 has been suggested to predispose rheumatoid arthritis (RA) patients to develop more aggressive disease. However, the potential association between CD4+CD28null T cells and early atherosclerotic changes in RA has never been investigated. Methods and Results - The number of circulating CD4+CD28null cells was evaluated in 87 RA and 33 control subjects who also underwent evaluation of carotid artery intima-media thickness (IMT) and endothelial function via flow-mediated vasodilation (FMV). Patients had higher IMT and lower FMV compared with control subjects. The frequency of CD4+CD28null cells was significantly higher in patients than in control subjects. Twenty patients with persistent expansion of circulating CD4+CD28null cells had more marked increase of carotid artery IMT and stronger decrease of brachial artery FMV. Blockade of tumor necrosis factor-α led to a partial reappearance of the CD28 molecule on the CD4+ cell surface. Conclusions - Circulating CD4+CD28null lymphocytes are increased in RA. Patients with persistent CD4+CD28null cell expansion show preclinical atherosclerotic changes, including arterial endothelial dysfunction and carotid artery wall thickening, more significantly than patients without expansion. These findings suggest a contribution of this cell subset in atheroma development in RA. Moreover, the demonstration that tumor necrosis factor-α blockade is able to reverse, at least in part, the CD28 deficiency on the CD4+ cell surface may be of interest for possible innovative therapeutic strategies in cardiovascular diseases.
KW - Arthritis, rheumatoid
KW - Cells
KW - Endothelium
KW - Vasodilation
UR - http://www.scopus.com/inward/record.url?scp=2942547418&partnerID=8YFLogxK
U2 - 10.1161/01.CIR.0000131450.66017.B3
DO - 10.1161/01.CIR.0000131450.66017.B3
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AN - SCOPUS:2942547418
SN - 0009-7322
VL - 109
SP - 2744
EP - 2748
JO - Circulation
JF - Circulation
IS - 22
ER -