Clinical Information

The complement system membrane attack complex (MAC) is formed by the C5b fragment along with C6, C7, C8 and several C9 molecules. This complex is recognized by multiple names, including MAC, terminal complement complex and C5b-9. Laboratory tests measure the amount of soluble C5b-9 (sC5b-9) complex. The formation of C5b-9 and sC5b-9 is a consequence of activation of the complement system by either the classical, lectin, or alternative pathways. Therefore, measurement of the sC5b-9 complex can be used as a surrogate marker of terminal complement activation via all complement pathways.

Elevated concentrations of C5b-9 are associated with the development of transplant-associated thrombotic microangiopathy (TA-TMA), a complication of hematopoietic stem cell transplant.(1-3) Patients with higher sC5b-9 concentrations at baseline may require the use of higher doses of eculizumab to treat TA-TMA,(4) especially in children. Because of this association, measurement of sC5b-9 before transplant as part of a diagnostic evaluation and then repeat measurements during therapy have been proposed as tools to follow-up patients.(5) Importantly, while the elevation of sC5b-9 has shown very high sensitivity for TA-TMA, it has shown only a modest specificity, ranging from 40% to 50%, and the increased sC5b-9 may be found in other transplant complications as well as several other conditions where complement activation may occur: immune-complex disease, infection, atypical hemolytic uremic syndrome, C3 glomerulopathies, etc. A panel of complement tests, such as AHUSD / Atypical Hemolytic Uremic Syndrome Complement Panel, Serum and Plasma, may provide additional information on the extent of the complement activation, along with the information of which pathway is most dysregulated.