Enhanced Fcgamma receptor I, alphaMbeta2 integrin receptor expression by monocytes and neutrophils in rheumatoid arthritis: interaction with platelets.
OBJECTIVE
To investigate platelet and leukocyte activation and interaction in patients with rheumatoid arthritis (RA) and the effect of methotrexate (MTX) or anti-tumor necrosis factor-a (TNF-a) treatment on these variables.


METHODS
Four-color flow cytometry analysis was performed for quantitative measurement of platelet (P-selectin, PAC-1) and leukocyte (CD11b, CD64) activation markers and estimation of percentage of leukocyte-platelet complexes in whole blood in 20 patients with RA before and after 6 weeks of therapy and in 20 controls. In addition, measures of soluble P-selectin (sP-selectin), beta-thromboglobulin, fibrinogen, prothrombin fragment 1+2, D-dimer, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin 6 (IL-6), and TNF-a and tender and swollen joint counts were carried out.


RESULTS
Before therapy, PAC-1 binding, expression of CD11b and CD64 on monocytes and neutrophils, circulating levels of monocyte (CD11b+ or CD64+)-platelet complexes, monocyte-PAC-1+ platelet complexes, CRP, ESR, IL-6, TNF-a, fibrinogen, D-dimer and sP-selectin were significantly higher in RA patients compared to controls. The anti-TNF-a therapy significantly reduced levels of monocyte-PAC-1+ platelet complexes, sP-selectin, CRP, ESR, IL-6, TNF-a, fibrinogen, and D-dimer and tender and swollen joint counts. CD64 expression on monocytes was significantly decreased by MTX therapy. PAC-1 binding was not inhibited by MTX or anti-TNF-a.


CONCLUSIONS
Increased platelet and leukocyte activation and increased formation of leukocyte-platelet complexes in patients with RA suggest a status of simultaneous activation of the immune and hemostatic systems.
Bunescu
Andreia
A
Department of Clinical Chemistry, Capio Diagnostik, St. Göran's Hospital, 11281 Stockholm, Sweden. Andreia.Bunescu@capio.se
Seideman
Peter
P
Lenkei
Rodica
R
Levin
Klas
K
Egberg
Nils
N
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D015415:Biomarkers / Q000032:analysis; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D000069285:Infliximab; D016023:Integrins; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D019007:P-Selectin / Q000378:metabolism*; D011336:Probability; D011379:Prognosis; D017452:Receptors, IgG / Q000032:analysis / Q000378:metabolism*; D012016:Reference Values; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D016023:Integrins; D019007:P-Selectin; D017452:Receptors, IgG; D000069285:Infliximab; D008727:Methotrexate