van den Arie Berg

The significance of parenchymal changes of acute cellular rejection in predicting chronic liver graft rejection

Background. Chronic rejection (CR) in liver allografts shows a rapid onset and progressive course, leading to graft failure within the first year after transplantation. Most cases are preceded by episodes of acute cellular rejection (AR), but histological features predictive for the transition toward CR are not well documented. Methods. We assessed the predictive value of centrilobular necrosis, central vein endothelialitis (CVE), central vein fibrosis, and lobular inflammation in the development of CR. One-week and one-month biopsy specimens of 12 patients with CR were compared with those of a control group consisting of 17 patients, who experienced AR without developing CR. The progress of the histological changes was further evaluated in follow-up biopsy specimens of the CR group taken at 2 months and beyond 3 months after transplantation. Results. Centrilobular necrosis, CVE, central vein fibrosis, and lobular inflammation were common features in both groups at 1 week. At 1 month, the incidence declined in the control group. The CR group showed an increased incidence and persistence of these features in the follow-up biopsy specimens. The incidence and median grade of severity of CVE was significantly higher in the CR group (P =0.04 and P <0.001). The severity of portal and lobular inflammation was also more pronounced in the CR group (P =0.01 and 0.068). Conversely, in the control group, the incidence of the lobular features decreased and the severity of CVE declined significantly (P =0.03). Conclusion. The shift from a predominantly portal-based process toward lobular graft damage represents the early transition of AR to CR, for which a modification of immunosuppression might be necessary to prevent graft loss.

Activation of complement receptor 3 on human monocytes by cross‐linking of very‐late antigen‐5 is mediated via protein tyrosine kinases

Bordetella pertussis interacts with very‐late antigen‐5 (VLA‐5) receptors on the human monocyte resulting in cross‐linking of these receptors followed by activation of complement receptor 3 (CR3) and firm adhesion of B. pertussis to these monocytes. In the present study we investigated whether protein tyrosine kinases are involved in the activation of CR3 on monocytes, which was assessed by the binding of C3bi‐coated erythrocytes (EC3bi). Pre‐incubation of monocytes with tyrphostin‐A47, a specific protein tyrosine kinase inhibitor, before adherence of the cells to an anti‐VLA‐5 monoclonal antibody‐coated surface, or addition of tyrphostin‐A47 within 10u2003min of the adherence to such surface, reduced the binding of EC3bi to monocytes significantly. Pre‐incubation of monocytes with tyrphostin‐A47 reduced the binding of B. pertussis to such monocytes as well. Inhibitors of protein kinase A and/or C had no effect on EC3bi binding to monocytes. Cross‐linking of VLA‐5 on monocytes resulted in tyrosine phosphorylation of several proteins. Together, these results indicate that protein tyrosine kinases are involved in the VLA‐5‐induced activation of CR3 on human monocytes.

Binding of Murine Antibodies Against Whole-Cell Pertussis Vaccine or Filamentous Haemagglutinin by Bordetella pertussis from Patients with Whooping Cough

In 1996 an unexpected rise in the incidence of whooping cough occurred in the Netherlands, and antigenic divergence between vaccine strains and clinical isolates has been suggested as a cause for this phenomenon. To investigate this assumption, the binding of murine antibodies against the whole‐cell pertussis vaccine or filamentous haemagglutinin, an important protective antigen, to a limited number of Bordetella pertussis strains isolated during different time‐periods (1991–92, 1994 and 1996) was assessed. The results showed that all strains were recognized equally well by these antisera, indicating that filamentous haemagglutinin was unchanged during the time‐periods examined. Although over the years changes have occurred in at least two surface proteins of B. pertussis, these changes are too subtle to be recognized by the antibodies raised in mice. Further research is required to assess whether antigenic variation of B. pertussis has an effect on protective immunity.