Vimentin/cardiolipin complex as a new antigenic target of the antiphospholipid syndrome.
Antiphospholipid syndrome (APS) is an autoimmune disease characterized by arterial and venous thrombosis, recurrent abortions, and antiphospholipid antibodies (aPL). However, it is possible to find patients with clinical signs of APS who persistently test negative for aPL (seronegative APS, or SN-APS). The aim of this study was to identify new antigenic target(s) of autoantibodies in APS patients, which may also be recognized in SN-APS. We tested sera from patients with SN-APS with a proteomic approach by analyzing endothelial cell-surface membrane proteins. Sera from SN-APS patients revealed 2 reactive spots corresponding to vimentin, a protein that is shown to bind cardiolipin in vitro. Antivimentin/cardiolipin antibodies were tested in 29 SN-APS patients, 40 APS patients, 30 patients with systemic lupus erythematosus, 30 with rheumatoid arthritis, 30 with venous or arterial thrombosis, and 32 healthy control patients. We observed that not only a large proportion of SN-APS patients but also almost all the APS patients displayed the presence of antivimentin/cardiolipin antibodies. To verify the possible pathogenic role of these autoantibodies, we demonstrated that affinity-purified antivimentin/cardiolipin antibodies induced interleukin receptor-associated kinase phosphorylation and nuclear factor-κB activation in endothelial cells. Our results prompt to identify vimentin as a "new" cofactor for aPL, which may represent a useful tool mainly in SN-APS patients.
Ortona
Elena
E
Dipartimento di Biologia Cellulare e Neuroscienze, Istituto Superiore di Sanità, Rome, Italy.
Capozzi
Antonella
A
Colasanti
Tania
T
Conti
Fabrizio
F
Alessandri
Cristiano
C
Longo
Agostina
A
Garofalo
Tina
T
Margutti
Paola
P
Misasi
Roberta
R
Khamashta
Munther A
MA
Hughes
Graham R V
GR
Valesini
Guido
G
Sorice
Maurizio
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D016736:Antiphospholipid Syndrome / Q000175:diagnosis* / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D002308:Cardiolipins / Q000276:immunology* / Q000378:metabolism; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000276:immunology; D011247:Pregnancy; D011485:Protein Binding; D014746:Vimentin / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
D001323:Autoantibodies; D002308:Cardiolipins; D016328:NF-kappa B; D014746:Vimentin; C507768:IRAK1 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases