Terminal Complement Pathway Deficiency in an Adult Patient with Meningococcal Sepsis

Figure 1

(a) Activation of the CP, AP, and LP. In the CP, C1q binds antigen-antibody complexes. After binding, C1r and C1s proteases cleave C4 and C2 resulting in the formation of a C4b2a (CP C3 convertase). This C3 convertase cleaves C3 into C3a and C3b forming the C4b2a3b (CP C5 convertase) which initiates the common terminal pathway and the formation of a MAC complex. In the AP, spontaneous hydrolysis of C3 forms C3(H2O) which associates with factor B and D to form the C3bBb (AP C3 convertase). Similar to CP, C3 is cleaved leading to the formation of a C3bBb3b complex (AP C5 convertase) and subsequent activation of the terminal pathway. The LP occurs through different initiators that bind high-density sugars of pathogens. After this binding, LP-associated serine proteases (MASP) form a complex with the recognition molecules to allow the cleavage of C4 and C2, similar to the CP. Properdin functions as a stabilizer of the membrane bound C3bBb and C3bBb3b. Factor H functions as a negative regulator of CP and AP by blocking formation of the AP C3 convertase, cleavage, and inactivation of C4b and preventing C1q binding to its ligands. Factor I mediates the cleavage and inactivation of C3b and C4b, blocking the formation of the C3 convertase. Red arrows indicate inhibitory routes, and green arrows indicate stabilizing routes. (b) Interpretation of CH50 and AP50 values in the diagnosis of complement deficiencies. Further testing for individual components in the complement pathway should be performed depending on this result.

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