TBPP_C1 Inhibitor

N-terminal tail heavily glycosylated (35% of MW), strong impact on half-life in plasma, impact of binding of LPS (protection of endotoxic shock), binding to selectins.

cryprecipitation, ion-exchange chr. , (salting out), pasteurization, (salting out), hydrophobic interaction chr., filtration, lyopilization

"the complement system", belongs to innate immune system, plasma proteins with several proteases activated only after cleavage (zymogens), 3 major activation pathways: classical, lectin, alternative, attraction of cellls to site of inflammation, attraction for phagocytosis, lysis of cells, shaping of the adaptive immune system, complement disregulation = chronic inflammatory / autoimmune diseases

pattern recognition molecules (C1q, MBL), proteases (C1r, C1s), complement components (C3-C9), complement regulators (C1 INH, MCP), complement receptors (CR1-4), targets of C1 Inhibitor: classical pathway: C1s, C1r (C1Inh form a covalent complex with C1rC1s = inactivation), lectin pathway: MASP1, MASP2, alternative pathway: C3b (prevents C3b deposition)

hemolytic assays (CH50): sensibilzation of erythrocytes with antibody, incubation, stopp reaction with EDTA, measurements of erythrocytes lysis. complement activation in normal human serum. complement deposition on human endothelial cells. Potentiation of C1 INH activity by glycosaminoglycans

key regulator of vascular permeability and inflammatory processes after tissue injury, released from prekallikrein by activated FXII (Hageman factor), releases bradykinin (which binds B2R) from kininogen, linked with coagulation, firbrinolytic as well as with renin-angiotensin system.

description Osler in 1888, symptoms: edema, start in childhood and persist throughout life, more than 150 different mutations, low levels or abnormal C1 INH, prevalence: 1:50'000, different types of HAE I-III (1: low level, normal function, 2: normal level, low function, 3: not C1 INH dependent, normal level and function, all autosomal dominant)

C1 INH: plasma derived or recombinant, kalbitor (kallikrein inhibitor), Icatibant (B-Receptor antagonist)