Summary
The presence of antiphospholipid antibodies (aPL) is strongly correlated with venous
and arterial thrombosis, fetal loss and thrombocytopenia. This relation is called
the antiphospholipid syndrome (APS). It is well recognized that thrombosis related
aPL are not directed against phospholipids alone, but to phospholipid bound plasma
proteins like β2-glycoprotein I (β2GPI). aPL that need β2GPI for the binding to negatively charged phospholipids are called anti-β2GPI-antibodies. Recently, a mutation in the gene encoding β2GPI has been described, which results in an amino acid substitution Trp316 into Ser316.
This Ser316-β2GPI did not bind to negatively charged phospholipids. Because only phospholipid bound
β2GPI is recognized by human anti-β2GPI-antibodies, it might be argued that individuals carrying the Trp316Ser mutation
are protected against the development of anti-β2GPI-antibodies.
To investigate this hypothesis, the prevalence of the Trp316Ser mutation was measured
in 170 systemic lupus erythematosus (SLE) patients and in 18 patients with the primary
antiphospholipid syndrome (PAPS) and the mutation was correlated with the presence
of anti-β2 GPI-antibodies. In the total patient group 1 homozygous patient and 21 heterozygous
patients were found. The allele frequency of the mutation in SLE patients with anti-β2GPI-antibodies (0.063) was comparable to that found in SLE patients without anti-β2-GPI-antibodies (0.062). These results indicate that the heterozygous presence of Trp316Ser
mutation does not prevent an individual from developing anti-β2GPI-antibodies. We showed that this can be explained by the concentration of Trp316-β2GPI in heterozygous patients, which is far above the minimal β2GPI level necessary for optimal phospholipid binding. In our single patient homozygous
for the Trp316Ser mutation no binding of β2GPI to the phospholipid surface was detected and no anti-β2GPI-antibodies were present in the plasma of this patient.
In conclusion, heterozygous Trp316Ser β2GPI persons are not protected against the development of anti-β2GPI-antibodies. To confirm that homozygotes do not develop anti-β2GPI-antibodies a very large population is needed, due to the relatively low prevalence
of the mutation.