Cleavage of IgG1 and IgG3 by gingipain K from Porphyromonas gingivalis may compromise host defense in progressive periodontitis

Degradation of immunoglobulins is an effective strategy of bacteria to evade the immune system. We have tested whether human IgG is a substrate for gingipain K of Porphyromonas gingivalis and found that the enzyme can hydrolyze subclass 1 and 3 of human IgG. The heavy chain of IgG(1) was cleaved at a single site within the hinge region, generating Fab and Fc fragments. IgG(3) was also cleaved within the heavy chain, but at several sites around the CH2 region. Investigation of the enzyme kinetics of IgG proteolysis by gingipain K, using FPLC- and isothermal titration calorimetry-based assays followed by Hill plots, revealed non-Michaelis-Menten kinetics involving a mechanism of positive cooperativity. In ex vivo studies, it was shown that gingipain K retained its IgG hydrolyzing activity in human plasma despite the high content of natural protease inhibitors; that IgG(1) cleavage products were detected in gingival crevicular fluid samples from patients with severe periodontitis; and that gingipain K treatment of serum samples from patients with high antibody titers against P. gingivalis significantly hindered opsonin-dependent phagocytosis of clinical isolates of P. gingivalis by neutrophils. Altogether, these findings underline a biological function of gingipain K as an IgG protease of pathophysiological importance.

Dominance, Competition, Compromise or Consensus? Explaining Decision-Making Structures

The previous chapter uncovered important differences between decision-making structures across the 11 processes investigated by this study. As we have noted, both historically and in much contemporary literature, the Swiss political system has been described as highly consensual. And yet, when we focus on differences between decision-making structures across different policy domains, important elements appear that point toward a more conflictual style of decision-making. Both when there is a power balance between coalitions and in the presence of a dominant coalition, coalition interactions are conflictual in the majority of cases. Based on the descriptive account of these differences in Chapter 4, the present chapter studies the conditions under which given decision-making structures emerge. Under which circumstances are actors able to form a dominant coalition, and which conditions lead to a situation where power is more evenly balanced between coalitions? Which conditions lead actors to develop a conflictual rather than a consensual type of interaction? Answering these questions can give us some indication of the factors responsible for different types of decision-making structures.