Variation of anti-Fas antibodies in different lots of intravenous immunoglobulin

Background and Objectives  Previous studies have presented evidence that human immunoglobulin G preparations for intravenous use contain antibodies directed against the death receptor Fas (CD95). The function of these antibodies was described as either antagonistic or agonistic; therefore, inhibiting or stimulating Fas-dependent apoptosis. Based on these reports, we asked whether the proportion of antagonistic and agonistic anti-Fas activities differs between different lots of intravenous immunoglobulin (IVIG). Variations between lots would open the possibility to preselect suitable lots of IVIG for different therapeutic purposes. Materials and Methods  Eleven lots of IVIG were tested for their ability to induce or inhibit Fas-dependent apoptosis. The biological significance of anti-Fas antibodies was confirmed by including anti-Fas antibodies purified from IVIG and IVIG depleted of anti-Fas antibodies in the study. Results  All 11 lots inhibited FasL-induced apoptosis. In addition, five lots stimulated apoptosis in the absence of FasL. Depletion of anti-Fas antibodies from IVIG abolished the capacity of IVIG to inhibit FasL-induced apoptosis, but reduced the ability to induce apoptosis only slightly. Conclusion  The inhibition of FasL-induced apoptosis by IVIG is because of the presence of antagonistic anti-Fas antibodies. The activity of these antibodies differs considerably between different lots. On the other hand, the induction of apoptosis by IVIG is probably because of the concerted action of a range of different antibodies. The variation in the proportion of stimulating and inhibiting anti-Fas activities between different lots of IVIG opens the possibility to preselect suitable lots for different therapeutic purposes.