Intravenous immunoglobulin contains detectable amounts of antiphospholipid antibodies.

High-dose intravenous (i.v.) immunoglobulin (Ig) has been shown to be effective in the treatment of several disorders, including bacterial and viral infections in primary and secondary immunodeficiency states, as well as in autoimmune diseases. Recently, successful results obtained by treatment with i.v. Ig in patients with recurrent abortions and antiphospholipid antibody syndrome (APS) have been summarized (Orvieto et al, 1991). As far as autoimmune disorders are concerned, the suggested mode of action of i.v. Ig includes competitive binding to macrophage receptors, increasing the number of T-suppressor cells, masking the recognition of class II major histocompatibility complex and immuno-manipulation consequent to favourable changes in the network of idiotypic interactions (Berkman et al, 1990). In the context of APS-related pregnancy loss, a pathogenic role of antiphospholipid antibodies, recognized as antiphospholipid (aPL) or anticardiolipin (aCL) on the basis of different antigens employed in commercial kits, might be supported by experimental studies, showing that passive transfer of aPL/aCL may have direct effects on the fecundity and outcome of pregnancy (Blank et al, 1991). As i.v. Ig is beneficial, a decrease in aPL/aCL levels following Ig infusion might be expected. However, this is not the case, in that the treatment may transiently suppress the lupus anticoagulant activity, but aPL/aCL levels decrease only slightly or remain elevated (Orvieto et al, 1991). As natural antibodies against phospholipids are recognized in humans (Alving, 1984) and commercial i.v. Ig are prepared from large pools of normal donors, we tested five commercial preparations licensed in Italy for the presence of IgG (GPL) and IgM (MPL) isotypes of aPL or anticardiolipin (aCL) antibodies detected by two ELISA commercial kits (Diagnostica Stago and Byk Gulden respectively). We also looked for antineutrophil cytoplasm antibodies (ANCA: antiMPO 1⁄4 C-ANCA, ANTI-PR3 1⁄4 P-ANCA) by ELISA (MEDIC) following suggestions that the presence of some amount of ANCA in i.v. Ig might explain the early increase in ANCA levels following i.v. Ig administration in vasculitis ( Jayne et al, 1991). Although ANCA levels were always undetectable, aPL and/or aCL were found in all the five samples of commercial preparations of Ig tested (Table I). These results may stimulate speculation on the reasons for the success of i.v. Ig in APS-related pregnancy loss. Previous reports supported the hypothesis that one mechanism of aPL/aCL production might be an immune response to myocardial injury, thus allowing the suggestion that ‘it is not beyond the realms of possibility that administration of exogenous aPL/aCL in the immediate postinfarct period, in a fashion analogous to the administration of anti-D to rhesus negative mothers, could prevent such sensitization’ (Morton et al, 1986). Might the beneficial effects of i.v. Ig in the context of APS-related pregnancy loss be dealing with the aPL/aCL entailed in i.v. Ig, as these antibodies could prevent (or overwhelm) some ongoing sensitization process? Obviously, many other potential mechanisms have to be investigated. A recent hypothesis suggests that aPL/aCL, as many other autoantibodies putatively related to pregnancy loss, are nothing more than an epiphenomenon due to some primary abnormality of T lymphocyte in recognizing self antibodies (Gleicher, 1994). In this sense, i.v. Ig could possibly correct these abnormalities of T lymphocytes, as well as providing anti-idiotypic antibodies. British Journal of Haematology, 1997, 96, 872–882