Background/Purpose:

Antiphospholipid Syndrome (APS) is an autoimmune rheumatic
disorder in which antiphospholipid antibodies (aPL) cause clinical sequelae including vascular events
(VE) and pregnancy morbidity (PM). The key antigen in APS is
beta-2-glycoprotein I (beta2GPI), which consists of five domains. The
N-terminal domain (DI) carries the main immunodominant
epitope. Current clinical ELISAs used in APS test for anti-cardiolipin
(CL) and anti- beta2GPI antibodies but increasing evidence suggests that
anti-DI levels may be more strongly associated with VE and PM. Patients with
SLE are often screened using current tests for aPL
and up to 40% are positive but the implications of a positive test for future
health of the patient are not clear. In this study we retrospectively explored
the prevalence of IgG anti-CL, anti-beta2GPI and anti-DI antibodies in stored
serum samples that had been collected prospectively within one year of
diagnosis in 501 patients with SLE and analysed associations between these
serological profiles and clinical outcomes.

Methods:

Samples from 501 patients with SLE, fulfilling revised ACR
criteria, had been taken and stored at -20 degrees C within one year of
diagnosis. All samples were tested for levels of IgG anti-CL, anti-beta2GPI and
anti-DI by ELISA. Results were expressed in absorbance units (AU) by comparison
with standard positive controls loaded on every plate. A positive test was
defined as an AU level > 99^th percentile of 100 healthy controls
and high positive was defined as double that level. Data on VE (venous or
arterial thrombosis or coronary disease) and pregnancy were obtained from
medical records and patient interviews. Fisher’s exact test was used to analyse
statistical associations between particular serological profiles and VE or PM.

Results:

The mean (SD) age of the 501 patients was 30 (12.2) years,
91% were female and 61% white. In the early disease samples, 68 were positive
for anti-CL, 24 for anti- beta2GPI and 146 for anti-DI. 30 patients were
double-positive for two of these aPL
and 9 were triple-positive. Using higher cut-off levels, 31, 6 and 36 were
high-positive for anti-CL, anti- beta2GPI and anti-DI respectively. Mean
follow-up time post-sample was 12.1 years (max 36 years). Full data on VE and
PM were available for 338 and 275 patients respectively. Table 1 shows
associations between particular serological profiles and occurrence of VE or
PM.

Conclusion:

38% of patients were positive for one or more aPL in early disease but only 15%
showed high positivity. Being double or triple-positive was most strongly
associated with VE (but not PM) – 40% of the double/triple positive patients
suffered VE in the follow-up period. Positivity for anti-beta2GPI was also
associated with VE. High positivity for anti-DI showed the strongest
association with PM.

 Table
1 – Association of different serological profiles in early disease with VE or
PM (* signifies statistically significant association<0.05)