Soluble Terminal Complement Complex (SC5b-9).
 

SC5b-9: The Soluble Terminal Complement Complex enzyme immunoassay (EIA) measures the amount of the SC5b-9 complex present in human plasma. The Terminal Complement Complex (TCC, SC5b-9) is generated by the assembly of C5 through C9 as a consequence of activation of the complement system by either the classical, lectin or alternative pathway. The membrane attack complex (MAC), a form of TCC, is a stable complex that mediates the irreversible target cell membrane damage associated with complement activation. Complexes formed in the absence of a target membrane bind to naturally occurring regulatory serum proteins, e.g. the S protein forming non-cytolytic complexes in plasma.^1,2 The SC5b-9 EIA test quantitates SC5b-9 in plasma. The drug eculizumab, a terminal complement inhibitor, has been shown to inhibit hemolysis in patients with paroxysmal nocturnal hemoglobinuria (PNH) and to inhibit complement-mediated thrombotic microangiopathy in patients with atypical HUS (aHUS).^3,4 Eculizumab is a humanized monoclonal antibody that binds to the complement protein C5 with high affinity, thereby inhibiting its cleavage to C5a and C5b and preventing the generation of the cytolytic terminal complement complex, C5b-9. Elevated plasma levels of SC5b-9 may be an indicator of an insufficient level of eculizumab to maintain blocking the formation of the terminal attack complex.^5,6 Atypical HUS patients have been shown to display increased levels of C3a, C5a and C5b-9 in plasma prior to treatment.^7,8 Elevated plasma levels of the biomarkers C3a C5a may reflect ongoing activation even though full inhibition of the global activity (CH50 and sC5b-9) has been demonstrated.^9,10

REFERENCES:

1. Podack, ER, Kolb, WP, and Müller-Eberhard, HJ. The C5b-6 complex: formation, isolation, and inhibition of its activity by lipoprotein and the S-protein of human serum. J Immunol. 1978; 120: 1841-8.
2. Podack, ER and Müller-Eberhard, HJ. Isolation of human S-protein, of an inhibitor of the membrane attack complex of complement. J Biol Chem. 1979; 254:9808-14.
3. Hillmen P, Hall C, Marsh JC, et al. Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2004; 350:552-9.
4. Legendre, CM, Licht, C, Muus, P, et al. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med 2013; 368:2169-81.
5. Prüfer, F, Scheiring, J, Sautter, S, et al. Terminal complement complex (C5b-9) in children with recurrent hemolytic uremic syndrome. Semin Thromb Hemost 2006; 32:121-7.
6. Zimmerhackl, LB, Hofer, J, Cortina G, et al. Prophylactic eculizumab after renal transplantation in atypical hemolytic-uremic syndrome. N Engl J Med. 2010; 362:1746-8.
7. Mache CJ, Acham-Roschitz B, Fremeaux-Bacchi V, Kirschfink M, Zipfel PF, Roedi S, Vester U, Ring E. Complement inhibitor eculizumab in atypical hemolytic uremic syndrome Clin J Am Soc Nephrol 2009: 4: 1312-16.
8. Wehling C, Amon O, Hohenstein B, Pape L, Bommer M, Kirschfink M. Eculizumab drug monitoring in serum and urine opens new insights into therapy of complement-medicated nephropathies. Mol Immunol 2013; 56: 257.
9. Spero R, Cataland V, Holers M, Geyer S, Yang S, and Wu HM. Biomarkers of the alternative pathway and terminal complement activity at presentation confirms the clinical diagnosis of aHUS and differentiates aHUS from TTP. Blood 2014; 123:3733-8.
10. Noris M, Galbusera M, Gastoldi S, Macor P, Banteria F, Bresin E, Tripodo C, Bettoni A, Donadelli R, Valoti E, Tedesco F, Amore A, Coppo R, Ruggenenti P, Gotti E and Remuzzi G. Dynamics of complement activation in aHUS and how to monitor eculizumab therapy. Blood 2014 124:1715-1726.