• antiphospholipid antibodies
• rheumatoid arthritis

We read with interest the letter entitled “Antiphospholipid antibodies and RA: presence of β₂GP1 independent aCL” by Bonnet et al published in the Annals in March 2001.¹ We believe that the letter needs additional clarification owing to inconsistencies in the terminology, methodology of antiphospholipid antibody (aPL) detection, and determination of positive values.

The use of the term “anticardiolipin antibodies” was somewhat misleading. The term was introduced and abbreviated as “aCL”, a group of antibodies detected in many conditions, but the β₂ glycoprotein 1 (β₂GP1) dependence of the aCL was not defined, even though the authors focused on β₂GP1 independent aCL. It is generally agreed that the term aCL, if not stated otherwise, defines the antibodies detected by the classical aCL enzyme linked immunosorbent assay (ELISA),^2,3—that is, both β₂GP1 dependent and β₂GP1 independent antibodies.

There were some potential methodological errors in determining β₂GP1 independent aCL. It was shown that antibodies against β₂GP1 (anti-β₂GP1) from patients with the antiphospholipid syndrome (APS) have the ability to bind β₂GP1 in complexes with cardiolipin only if the β₂GP1 concentration in solution is high enough. The threshold concentration of β₂GP1 was found to be just about 2 μg/ml, because no binding of anti-β₂GP1 was seen when serum samples were diluted 1:200 or more.⁴ As the physiological concentration of β₂GP1 in human serum is approximately 200 μg/ml, the threshold binding concentration is reached at a serum dilution of 1:100. In the presence of a relatively high concentration of endogenous β₂GP1, the statement that antibodies detected by this method are exclusively β₂GP1 independent is unjustified, as the sera containing high titres of …