Increased soluble endothelial adhesion molecules in rheumatoid arthritis correlate with circulating cytokines and depletion of CD45RO+ T-lymphocytes from blood stream.
Endothelial cells express adhesion molecules and release free forms (e.g., sELAM-1, sGMP-140, sICAM-1 and sVCAM-1). Compared with controls, the serum levels of these soluble adhesion molecules (SAM) were significantly increased in patients with rheumatoid arthritis. We investigated whether this was associated with the circulating cytokines and changes in peripheral blood T-lymphocyte (T-PBL) subsets. In healthy subjects, sELAM-1 correlated with the serum levels of Il-1 beta, Il-1 receptor antagonist (Il-1RA) and Il-6, while sGMP-140 was associated with Il-8, and sVCAM-1 was related to Il-7 and Il-8. Thus, already in controls, relations exist between the levels of SAM and circulating cytokines. The rheumatoid arthritis patients with low and high serum levels of IgA- and/or IgM-rheumatoid factors (RF) were separately analyzed. They have different cytokine profiles and showed distinct correlations. In patients with low RF, sGMP-140 and sVCAM-1 correlated with Il-1 beta, while sICAM-1 was associated with Il-7 and TNF-alpha. In patients with high RF, sELAM-1 correlated with Il-1RA, and sGMP-140 was associated with many cytokines (e.g., GM-CSF, MIP-1 alpha and TNF-alpha). In addition, lymphopenia (less than 1000 lymphocytes/microliters) was shown in 30% of the patients, and 20% (mostly with low RF levels) had reduced levels of "primed" CD45RO+ cells among T-PBL. In controls, cytokines (Il-7, Il-8 and GM-CSF), but not SAM, were associated with less CD45RO+ T-PBL. In patients with low RF only, sGMP-140 and sELAM-1 correlated with the depletion of "primed" CD4+ and CD8+ T-PBL respectively. In such patients, Il-1 beta and GM-CSF also correlated with less CD8+, CD45RO+ T-PBL. Thus, particularly in patients with low RF, increased SAM, possibly released by the endothelial cells, might reflect the cytokine-induced activation of the vascular endothelium and the extravasation of some CD45RO+ T-PBL.
Neidhart
M
M
Department of Rheumatology, University Hospital, Zurich.
Pataki
F
F
Fehr
K
K
D001172:Arthritis, Rheumatoid / Q000276:immunology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000302:isolation & purification*; D016207:Cytokines / Q000302:isolation & purification; D019040:E-Selectin; D006801:Humans; D017493:Leukocyte Common Antigens / Q000302:isolation & purification; D011971:Receptors, Immunologic / Q000302:isolation & purification*; D016028:Receptors, Leukocyte-Adhesion / Q000302:isolation & purification*; D013601:T-Lymphocytes / Q000276:immunology
D015815:Cell Adhesion Molecules; D016207:Cytokines; D019040:E-Selectin; D011971:Receptors, Immunologic; D016028:Receptors, Leukocyte-Adhesion; D017493:Leukocyte Common Antigens