PubMed · 4507665
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G S Gilchrist. 1972. Platelet disorders.. https://doi.org/10.1016/s0031-3955(16)32781-x
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BACKGROUND: Diagnosis of many immune-mediated diseases is helped by detection of antibodies directed against the pathogenetic (self or foreign) antigen. In coeliac disease (CD), we have a situation in which antiendomysial antibodies (EMA), which are not specific for the pathogenetic antigen, reach a specificity and sensitivity of detection of CD approaching 100%, whereas detection of antibodies against gliadin (AGA), the pathogenetic antigen, is far less specific and sensitive in diagnosis. No direct evidence of a relation between gluten/gliadin challenge and EMA production exists. We tried to establish whether the small intestine of CD patients is the site of EMA production and whether gliadin challenge could induce their release. METHODS: Small intestine biopsy samples from treated (23) and untreated (16) CD patients and controls (18) were cultured in vitro for 24-48 h in the presence of gliadin, another alimentary antigen, or medium. EMA and AGA were detected in the supernatants of these organ culture biopsy samples by ELISA and immunofluorescence technique, respectively. FINDINGS: No EMA were found in the culture supernatants of biopsy samples of 18 controls, whereas they were detected in the culture supernatants of all 16 untreated CD patients irrespective of gliadin challenge. Conversely, EMA were not detected in supernatants of biopsy samples cultured in medium only from 23 treated CD patients, but were detected in 17 of the 23 biopsy samples challenged with gliadin. INTERPRETATION: Our results suggest that a more complex pathogenetic mechanism than normally accepted is involved in CD. Furthermore, our findings raise the possibility that EMA, or the antigen recognised by them, are involved directly in the pathogenesis of CD.
OBJECTIVE: To evaluate the risk for development of antibodies to factor VIII (factor VIII inhibitors) during and after interferon therapy in patients with hemophilia A and chronic hepatitis C infection. DESIGN: Patients were divided into two treatment groups and an untreated control group. Test results from the two treatment groups were compared with those from the control group. SETTING: 3 clinical centers in the Netherlands. PATIENTS: 35 men with hemophilia A who had acquired hepatitis C through the use of plasma-derived clotting factor concentrates. MEASUREMENTS: Patients were tested for factor VIII inhibitors before the start of interferon therapy and every 6 months thereafter. RESULTS: 21 patients with hemophilia A received interferon therapy for chronic hepatitis C infection for a mean of 19.5 months (range, 0.5 to 36 months). In 2 patients, inhibitors were detected on one occasion (maximum titer, 1.2 Bethesda units/mL) during interferon therapy. In 3 patients who were known to have had inhibitors before interferon therapy, no anamnestic reaction was seen during treatment. In 3 of 14 untreated controls who were followed for a mean of 28 months (range, 18 to 40 months), inhibitors were detected on one occasion (maximum titer, 2.3 Bethesda units/mL). CONCLUSION: Long-term interferon therapy in patients with hemophilia did not increase the risk for development of factor VIII inhibitors.
We have developed a model of the early events that occur during a primary antibody response to a T cell-dependent antigen. Within secondary lymphoid organs, B cell proliferation in response to antigen injection gives rise to two kinds of transient structures: foci that develop in the T cell area, and germinal centers, that develop in the secondary follicles of the B cell area. Foci give rise to plasma cells that are responsible for the majority of early circulating antibody, whereas germinal centers are sites of somatic mutation and memory cell formation. Here we model the cell-cell interactions and cell population kinetics involved in the generation of antibody-forming cell foci, and compare our model with experimental data. We focus on fundamental issues involving the control of B cell proliferation and differentiation, using simple kinetic models that depend on direct cell-cell interactions and on the action of cytokines. We show that with realistic parameter assumptions our model can account for both the rapid cellular expansion and the differentiation of B cells into antibody-secreting cells. By summing the expected antibody production of all the plasmablasts and plasma cells that are generated during the focus response we can account for much of the antibody observed in the serum of mice during a primary response. Lastly, we compare the predictions of our model for two different scenarios for the control of B cell proliferation. In one model, we assume that B cells, once activated, proliferate under the control of cytokines without direct interaction with activated T cells. In the other model, we assume that after dividing B cells return to rest and require a contact-dependent signal from an activated T cell to divide again. The first model gives rise to large foci and antibody levels similar to that observed in experiment, whereas the latter model gives rise to four-fold smaller foci and to circulating antibody levels that are one order of magnitude lower than typical experimental values. This result suggests that B cells may be able to divide without further contact with T cells once a cognate interaction has occurred.