C1q assay to detect complement fixing antibodies

Complement

In the HLA lab we are consistently confronted with the issue of whether a detected donor-specific antibody is present or absent.  Even if a DSA is found the ultimate question still remains: is this antibody clinically relevant?   The advent of the C1q Assay now allows labs to screen sera for a sub-set of immunoglobulin G (IgG) antibodies which bind complement.  This assay is easy to run in parallel with and a single antigen bead assay and informs the lab which antibodies present in the sera are complement-fixing.  Studies have should this assay can be predictive of antibody mediated rejection.

IgM antibodies are the best at recuiting complement, however their role in transplant rejection is unclear.   IgM DSA do not lead to hyperacute rejection however, IgM antibodies against donor HLA have been shown to decrease both kidney and heart allograft survival.  The C1q asssay only detects complement fixing IgG so the role of IgM fixing complement and its clinical relevance will have to wait.

Of the IgG only certain subclasses are capable of activating the complement cascasde.  This includes IgG 1, 2, 3  of which IgG3 is best and IgG4 does not fix complement.   Using this assay will bypass IgG4 as not clinically relevant.   Although this has not be proven more studies need to be done to address the subclasses of IgG and clinical outcome.  A recent 2011 study demonstrated patients with weak or no complement-activating DSA had a lower incidence of antibody mediated rejection.