Godište 35 supplement 2 - Institut za reumatologiju

SISTEMSKE BOLESTI VEZIVNOG TKIVA
PREDAVANJE PO POZIVU (PP)
PP 06.
DO CLINICIANS KNOW ENOUGH ABOUT ANITIBODIES AGAINST BETA2-GLYCOPROTEIN I?
Rozman B, Čučnik S, Božič B, Ambrožič A, Lukač J, Tomšič M, Kveder T
Dept. of rheumatology, Medical Centre Ljubljana, Ljubljana, Slovenia
Antibodies against beta2-glycoprotein I (anti-beta2-GPI) are beside anticardiolipin antibodies (aCL) among the most
commonly detected subset of antiphospholipid antibodies (aPL). They are more speciffic for APS related manifestations than
aCL. The inter-laboratory comparability of anti-beta2-GPI enzyme linked immunosorbent assay (anti-beta2-GPI ELISA)
results is hardly possible due to methodological differences, lack of international standards and different cut-off values. We
have already shown several methodological aspects influencing anti-beta2-GPI ELISA results (blocking agents, different
plates). In 2000 we tested monoclonal antibodies HCAL (IgG) and EY2C9 (IgM), both kindly provided by T. Koike, as
possible calibrators. Two years later we participated in a multicentre study on anti-beta2-GPI standardization. Despite large
variability of anti-beta2-GPI measurments among centers, the overall agreement on the results obtained for high- and mediumpositive
samples was good. However, until today ELISA method for the detection of anti-beta2-GPI has stayed unstandardized,
and anti-beta2-GPI not quantitatively evaluated. Anti-beta2-GPI have so far not been officialy included into the APS
laboratory criteria.
Moreover, there is an enormous heterogeneity among anti-beta2-GPI with substantial differences including epitopic specificity,
avidity, light chain type or IgG subclass distribution and others. We previously reported of different epitopic specificities, and
different in vitro behaviour using giant phospolipid vesicles. Additionaly, we studed the binding of anti-beta2-GPI to human
and bovine beta2-GPI. We found typical binding patterns. In children with atopic dermatitis (AD) and without manifestation of
APS the binding only to human beta2-GPI significantly decreased during the follow-up and the binding to bovine beta2-GPI
did not change significantly. In contrast, significantly higher bindings to human beta2-GPI was observed predominantly in
patients with APS duration over 10 years when compared to patients with shorter APS duration or patients with the presence of
anti-beta2-GPI without any APS related manifestations. This phenomenon might reflect different autoimmune response –
clonal selection in AD children with non-thrombogenic anti-beta2-GPI and autoantibody maturation in APS patients. Further,
we focused on anti-beta2-GPI avidity. Low- , medium- and high-avidity antibodies were detected in patients with APS and
SLE. High-avidity anti-beta2-GPI prevailed in APS patients and were associated with thrombosis, in particular with venous
thrombosis. In individual patients we were not able to demonstrate any clear temporal relationship between high-avidity antibeta2-GPI
and clinical manifestations of APS. Our participation in a multicentre study showed APS patients to produce
antibodies against different peptides, very common on bacteria and viruses. The study opened an important issue of what role
do infecting agents have in triggering APS. Most recently we studed the prevalence of anti-beta2-GPI in different infections
including Lyme boreliosis, tick encephalomeningitis, hepatitis C, severe bacterial infections and hepatitis B vaccination. Antibeta2-GPI
of different Ig classes ranged from 2,5% to 16,5%.