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Publications (2)6.48 Total impact

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    ABSTRACT: 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. 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. 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. 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.
    Vox Sanguinis 06/2008; 94(4):334-41. · 2.85 Impact Factor
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    ABSTRACT: A thorough understanding of the naturally occurring events in the immune system in response to carcinogenesis will facilitate the development of strategies for the immunoprevention of cancer. The adenoma-carcinoma sequence in the human colon is a well-established clinical example of multi-step carcinogenesis and can be used for immunological studies. Based on previous observations that both apoptosis and the expression of Fas (Apo-1, CD95) are altered during carcinogenesis in the human colon, we asked the question whether serum titers of autoantibodies against Fas show any modification during the adenoma-carcinoma sequence. Healthy controls (38), patients with colorectal adenomas (38) and patients with colorectal adenocarcinomas (21) were investigated. Anti-Fas antibody titers were found to be significantly higher in patients with colorectal adenomas than in healthy controls and higher still in patients with colorectal adenocarcinomas. This increase in anti-Fas autoantibody titers during carcinogenesis might reflect the activation of natural defense mechanisms by the immune system.
    Cancer Immunology and Immunotherapy 11/2005; 54(10):1038-42. · 3.64 Impact Factor