1. Figure 1 The complement system and its targets
Figure 1 | The complement system and its targets. The complement system is typically thought to involve three main pathways. The classical pathway is activated by binding of the C1 complex, comprising C1q, C1r and C1s, to antibodies, which in turn cleave complement components C4 and C2. The lectin pathway is activated through the recognition of carbohydrates by mannose-binding lectin (MBL) or recognition of N-acetylglucosamine residues by ficolins. Upon binding, MBL associated serine proteases (MASPs) become activated and cleave C4 and C2. The alternative pathway is activated through the spontaneous activation of C3b. All three pathways lead to cleavage of C3, resulting in generation of the C5b−9 complex, known as the membrane attack complex (MAC). Approaches to inhibit the complement system can be categorized into five main groups. (1), agents that disrupt the initiating complexes or inhibit initiating enzymes of the lectin and classical pathways (for example, neutralizing monoclonal antibodies against MBL, C1q, C1s or MASP) or enzymes that inhibit complement initiation (for example, the C1 inhibitor, C1INH, and nafamostat mesilate). (2), agents that inhibit activating enzymes of the alternative pathway (for example, humanized immunoglobulin G1 (lampalizumab) and small-molecule protease inhibitors). (3), agents that inhibit C3 convertases and/or C3 activity (for example, C1INH). (4), agents that inhibit C5 convertases and/or C5 activity (for example, eculizumab, coversin and C5-specific aptamers). (5), agents that inhibit MAC function (for example, soluble recombinant CD59).
Flyvbjerg, A. (2017) The role of the complement system in diabetic nephropathy
Nat. Rev. Nephrol. doi: /nrneph