Background/Purpose:
Increased levels of antibodies against different serine proteases (SP) have been identified in patients with the Antiphospholipid Syndrome (APS) compared with healthy controls. These anti-SP antibodies have been shown to alter the function of these coagulation factors, hence may be important in the pathogenesis of thrombotic manifestations of the APS. Few studies however, have examined the prevalence of anti-SP antibodies in patients with other autoimmune rheumatic disease (ARD). Previously, we found raised levels of IgG against the SP – thrombin (Thr) in patients with APS as well as patients with systemic lupus erythematosus (SLE) who lacked APS compared with healthy controls. Therefore, in this study, we examined the prevalence and specificity of anti-SP antibodies in patients with APS compared with other ARD and healthy controls.
Methods:
Serum was obtained from 265 patients (at University College London Hospital) with: APS, n=59; SLE and no APS (SLE/APS-), n=106; rheumatoid arthritis (RA), n=30; Sjögren’s syndrome (SS), n=25, myositis (Myo), n=23; systemic sclerosis (SSc), n=22; and 40 healthy controls (HC). Of the patients with APS: 34 had primary APS and 25 had SLE/APS; whilst 46 had thrombotic and 13 non-thrombotic APS. In patients with SLE/APS- 57 were aPL positve (SLE/aPL+) and 49 aPL negative (SLE/aPL-). All other ARD and HC were aPL negative. Serum was tested for the presence of IgG directed against: – Thr; Factor Xa (FXa); Factor VIIa (FVIIa); and phosphatidylserine (PS)/FXa complexes by ELISA. Results were expressed as percentage of binding compared with a positive serum control and a positive value was defined as being ≥ 3SD above the mean of healthy controls.
Results:
IgG anti-FXa antibodies were only found in patients with SLE (n=52, 49.1%) and APS (n=20, 34.5%) whilst healthy and all other disease control groups completely (n=0) lacked these IgG (p<0.05). IgG anti-Thr antibodies were also found in patients with APS (n=21,36.2%) and SLE/APS- (n=59, 55.7%) more frequently than in HC (n=2, 5%, p<0.05). In contrast, to anti-FXa IgG the detection of anti-Thr IgG lacked specificity as they were also found in patients with RA (n=9, 30%), SS (n=10, 40%), Myo (n=11, 47.8%) and SSc (n=6, 27.3%) at frequencies which were not significantly different compared with APS but significantly increased in SLE/APS- compared with RA (p<0.05) and SSc (p<0.01). IgG against anti-PS/FXa complexes were found more frequently (p<0.05) only in patients with SLE/APS- (n=35, 33%) compared with APS (n=8, 13.8%), SS (n=1, 4%), Myo (n=1, 4.3%), SSc (n=0) and HC (n=0) groups. There were no significant correlations between frequency of any of the anti-SP antibodies tested or with aPL positivity. Furthermore, the prevalence of anti-SP IgG in the APS group was not specific to patients with SLE/APS.
Conclusion:
Anti-Thr, anti-FVIIa, anti-FXa and anti-PS/FXa IgG are not specific to patients with APS. Our finding that anti-FXa IgG were unique to patients with APS and SLE/APS- may indicate that these IgG interfere with the inflammatory rather than coagulant effects of FXa. Further experiments are now underway to clarify the precise pathological and diagnostic significance of anti-FXa IgG in these patients.
Disclosure:
B. Artim-Esen,
None;
C. Pericleous,
None;
I. Mackie,
None;
Y. Ioannou,
None;
A. Rahman,
None;
D. A. Isenberg,
None;
I. Giles,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-factor-xa-antibodies-are-significantly-increased-in-patients-with-systemic-lupus-erythematosus-and-antiphospholipid-syndrome/