Background/Purpose:

Patients with SLE have an increased risk of cardiovascular disease
(CVD), which is not fully explained by traditional risk factors and may be mediated
by systemic inflammation and autoantibodies.  Increasing interest has focussed upon
the involvement of pro-coagulant serine proteases (SP), thrombin (Thr) and
Factor (F)Xa, in atherosclerotic plaque formation. These SP have extended
cellular/inflammatory effects beyond coagulation through their activation of
protease activated receptors (PARs). Direct inhibitors of FXa and Thr have been
shown to reduce pro-inflammatory effects and stabilise atherosclerotic plaque
in ApoE mice. Levels of anti-FXa and anti-Thr IgG are raised in patients with
SLE compared with healthy controls, but the effects of these
IgG on atherosclerosis are unknown. Here we explore associations between presence
and number of sub-clinical atherosclerotic plaques detected by a vascular
ultrasound study in 100 patients with SLE and the presence of anti-FXa and/or
anti-Thr in the same patients.

Methods:

Carotid and femoral arteries of 100 patients fulfilling ACR criteria for
SLE but with no history of previous CVD were scanned by ultrasound.  We recorded presence of plaque, number
of plaque sites, total plaque area and intima media thickness. Serum samples from these patients, taken at or near the time of
scanning, were tested for anti-FXa and anti-Thr IgG by ELISA.
Statistical analysis of the association of antibody positivity/negativity and
presence/absence of plaque was determined by chi² test.

Results:

Of the 100 patients, 95% were female with mean age of 45.2 (range 20-66,
SD 12.4) years. Overall, 36% had plaque and 64% had no plaque.  Anti-FXa IgG were found in 44% and
anti-Thr IgG in 31% of all patients. Anti-FXa IgG positivity was seen in 33/64
(52%) of patients without plaque and 11/36 (31%) of patients with plaque (p<0.04). Among the 36
patients with plaque, the number of plaque sites per patient was lower in
anti-FXa positive than in anti-FXa IgG negative patients (p<0.02). Although
anti-Thr IgG positivity was also higher in patients without plaque (22/64 =
39%) compared to patients with plaque (9/36  = 25%), this difference did not reach
statistical significance (p=0.3). There was no association between anti-Thr positivity and
number of plaque sites.

Conclusion:

Patients with SLE who were positive for anti-FXa IgG had reduced
atherosclerotic plaque burden (presence and total number of sites) compared
with patients who were anti-FXa IgG negative. A similar relationship however,
was not found between anti-Thr IgG and plaque. Further research is now required
to determine whether anti-FXa IgG may be protective against the pro-atherogenic
effects of FXa in patients with SLE.