Antigenic mimicry has been proposed as a major mechanism by which viruses could trigger the development of immune thrombocytopenic purpura (ITP). However, because antigenic mimicry implies epitope similarities between viral and self antigens, it is difficult to understand how widely different viruses can be involved by this sole mechanism in the pathogenesis of ITP. Here, we report that in mice treated with antiplatelet antibodies at a dose insufficient to induce clinical disease by themselves, infection with lactate dehydrogenase-elevating virus (LDV) was followed by severe thrombocytopenia and by the appearance of petechiae similar to those observed in patients with ITP. A similar exacerbation of antiplateletmediated thrombocytopenia was induced by mouse hepatitis virus. This enhancement of antiplatelet antibody pathogenicity by LDV was not observed with F(ab) 2 fragments, suggesting that phagocytosis was involved in platelet destruction. Treatment of mice with clodronate-containing liposomes and with total immunoglobulin G (IgG) indicated that platelets were cleared by macrophages. The increase of thrombocytopenia triggered by LDV after administration of antiplatelet antibodies was largely suppressed in animals deficient for ␥-interferon receptor. Together, these results suggest that viruses may exacerbate autoantibody-mediated ITP by activating macrophages through ␥-interferon production, a mechanism that may account for the pathogenic similarities of multiple infectious agents. (Blood. 2004;

SUMMARY S-100 protein was determined by Particle Counting ImmunoAssay in the CSF of patients with various neurological disorders. With a limit of sensitivity of 2 5 ,ug/l this brain-specific protein was detected only in samples from patients with acute damage of the central nervous system, particularly in compression of the spinal cord by tumour, ischaemic disorders, subarachnoid bleeding and haematoma, and viral or suspected viral infections. Our results support the assumption that S-100 is a reliable index of central nervous system damage and that changes in its concentration could have a prognostic value.S-100 protein is an acidic protein of molecular weight 21,000' found essentially in the nervous system of vertebrates. This protein is called "S-100" because of its solubility in 100% saturated ammonium sulphate at neutral pH. A characteristic of S-100 is its structural changes caused by calcium ions.3 S-100 is, in fact, a family of proteins4`8 shown by complement fixation and cross-immunoelectrophoresis9 to be antigenically different. Two main types have been described.67 S-100a containing two different subunits (a and fi subunits) and S100b, two identical subunits (3 subunits).S-100, the function of which is still unknown, is located mainly in the astrocytes'0-'9 but has also been detected in

We have previously reported on the induction, in mice, of a systemic (splenic) immune response with IgA as the dominant antibody, as a result of a short (4 day) intragastric immunization course with foreign erythrocytes. This response was followed by a prolonged period of hyporesponsiveness to similarly administered antigen. Here it is shown that this hyporesponsiveness is also manifested towards antigen given intraperitoneally, and that one is therefore dealing with tolerance, not with failure to absorb antigen from the gut. In contrast, mice primed parenterally and then challenged intragastrically behaved as if never having any previous contact with the antigen, i.e., with a primary-type splenic response of predominant IgA character. This agrees with our former conclusion that splenic responses to enterically absorbed antigen reflect colonization of the spleen by cells sensitized locally in the gut wall, a site not readily primed by the parenteral route. Serum from intragastrically immunized mice contained a very active tolerogen. In vivo, it was capable of conferring tolerance to nonimmune recipient mice. In vitro, it paralyzed the activity of antibody-producing cells. Inhibitory sera has weak antibody activity, restricted to the IgA class, and contained immune complexes reacting with rheumatoid factor but not with C1q. Elimination of these complexes by means by insolubilized rheumatoid factor abolished the tolerogenic effect. In conclusion, the enterically induced tolerogen seems to consist of immune complexes with IgA as the antibody.

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