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Abstract

The aim of this study was to evaluate a possible association between lymphocyte subsets and intima media thickness (IMT) of carotid arteries in primary antiphospholipid syndrome (PAPS). We used a cross-sectional study on PAPS patients (n = 18) and healthy controls (n = 16). IgG anti-cardiolipin antibody (aCL), IgG anti-β₂glycoprotein-I (anti-β₂GPI), IgG anti-β₂glycoprotein-I complexed to oxidized low-density lipoprotein (oxLDL) and to a specific oxidized moiety of LDL (oxLig1), and β₂GPI-oxLDL were measured by ELISA. Lymphocyte immunophenotyping was performed using pairs of monoclonal antibodies directly labelled with fluorescein isothiocyanate, or phycoerythrin or phycoerythrin-Texas-red-X. Intima media thickness (IMT) of carotid arteries was determined by high-resolution sonography. Total peripheral blood lymphocytes did not differ between PAPS and controls. Memory CD4+/CD45RO + T cells were lower in PAPS than controls (P = 0.0007) as well as CD16+56+ natural killer cells (P = 0.02). In PAPS memory T CD45RO + cells positively correlated with IgG anti-β2GPI-oxLig1 (P = 0.002) and to IMT of carotid arteries (common carotid P = 0.02, bifurcation P = 0.007). Naïve CD4+/CD45RA+ T cells inversely correlated with β2GPI-oxLDL (P = 0.009). The relation between IgG anti-β2GPI-oxLig1 and IMT of carotid arteries with memory CD45RO + T lymphocytes suggests a role for the latter in PAPS related atherogenesis.

Keywords

antiphospholipid antibodies atherosclerosis IgG anti-β2GPI-oxLig1 lymphocytes

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References

Wilson WA , Gharavi AE , Koike T et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop . Arthritis Rheum 1999; 42: 1309-1311 .

Sanchez-Guerrero J. Some patients with primary antiphospholipid syndrome have increased CD5+ B cells that correlate with levels of IgM antiphospholipid antibodies . Clin Exp Rheumatol 1991; 9: 501-505 .

Papo T , Piette JC , Legac E et al. T lymphocyte subsets in primary antiphospholipid syndrome . J Rheumatol 1994; 21: 2242-2245 .

George J , Afek A , Gilburd B et al. Induction of early atherosclerosis in LDL-receptor-deficient mice immunized with beta2-glycoprotein I . Circulation 1998; 98: 1108-1115 .

Medina G , Casaos D , Jara LJ et al. Increased carotid artery intima-media thickness may be associated with stroke in primary antiphospholipid syndrome . Ann Rheum Dis 2003; 62: 607-610 .

Ames PRJ , Margarita A , Sokoll K , Weston M , Iannaccone L , Brancaccio V. Atherosclerosis in primary antiphospholipid syndrome . Ann Rheum Dis 2005; 64: 315-317 .

Hansson GK. Immune mechanisms in atherosclerosis . Arterioscler Thromb Vasc Biol 2001; 21: 1876-1890 .

Tanigawa T , Kitamura A , Yamagishi K et al. Relationships of differential leukocyte and lymphocyte subpopulations with carotid atherosclerosis in elderly men . J Clin Immunol 2003; 23: 469-476 .

Greaves M , Cohen H , Machin SJ , Mackie I. Guidelines on the investigation and management of the antiphospholipid syndrome . Br J Haematol 2000; 109: 704-711 .

10.

Kobayashi K , Kishi M , Atsumi T et al. Circulating oxidized LDL forms complexes with beta2-glycoprotein I: implication as an atherogenic autoantigen . J Lipid Res 2003; 44: 716-726 .

11.

Heiss G , Sharrett AR , Barnes R , Chambless LE , Szklo M , Alzola C for the ARIC investigators . Carotid atherosclerosis measured by B-mode ultrasound in populations: associations with cardiovascular risk factors in the ARIC study . AM J Epidemiol 1991; 134: 250-256 .

12.

Tan EM , Cohen AS , Fries JF et al. The 1982 revised criteria for the classification of SLE . Arthritis Rheum 1982; 25: 1271-1277 .

13.

De Bruyere M. Developmental and maturation changes in human blood lymphocyte subpopulations . Immunol Today 1992; 13: 215-218 .

14.

Becker H , Langrock A , Federlin K. Imbalance of CD4+ lymphocyte subsets in patients with mixed connective tissue disease . Clin Exp Immunol 1992; 88: 91-95 .

15.

Morimoto C , Steinberg AD , Letvin NL et al. A defect of immunoregulatory T cell subsets in systemic lupus erythematosus patients demonstrated with anti-2H4 antibody . J Clin Invest 1987; 79: 762-768 .

16.

Zhou X , Nicoletti A , Elhage R , Hansson GK. Transfer of CD4+ T cells aggravates atherosclerosis in immunodeficient apolipoprotein E knockout mice . Circulation 2000; 12: 2919-2922 .

17.

Hansson GK , Holm J , Jonasson L. Detection of activated T lymphocytes in the human atherosclerotic plaque . Am J Pathol 1989; 135: 169-175 .

18.

Stemme S , Holm J , Hansson GK. T lymphocytes in human atherosclerotic plaque are memory cells expressing CD45RO and the integrin VLA-1 . Arterioscler Thromb 1992; 12: 206-211 .

19.

George J , Harats D , Gilburd B et al. Immunolocalization of beta2- glycoprotein I (apolipoprotein H) to human atherosclerotic plaques: potential implications for lesion progression . Circulation 1999; 99: 2227-2230 .

20.

Visvanathan S , McNeil HP. Cellular immunity to beta 2-glycoprotein-1 in patients with the antiphospholipid syndrome . J Immunol 1999; 162: 6919-6925 .

21.

Lopez D , Kobayashi K , Merrill JT , Matsuura E , Lopez LR. IgG autoantibodies against beta2-glycoprotein I complexed with a lipid ligand derived from oxidized low-density lipoprotein are associated with arterial thrombosis in antiphospholipid syndrome . Clin Dev Immunol 2003; 10: 203-211 .

22.

Lopez D , Garcia-Valladares I , Palafox-Sanchez CA et al. Oxidized low-density lipoprotein/beta2-glycoprotein I complexes and autoantibodies to oxLig-1/beta2-glycoprotein I in patients with systemic lupus erythematosus and antiphospholipid syndrome . Am J Clin Pathol 2004; 121: 426-436 .

Lymphocyte subpopulations and intima media thickness in primary antiphospholipd syndrome

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