CRP-MEDIATED ACTIVATION OF COMPLEMENT IN-VIVO - ASSESSMENT BY MEASURING CIRCULATING COMPLEMENT-C-REACTIVE PROTEIN COMPLEXES

The in vivo function of C-reactive protein (CRP) is unknown. Among the in vitro functions assigned to CRP is the ability to activate complem ent via the classical pathway. To date, there is no evidence supportin g that CRP exerts this function in vivo. We here show a novel approach to assess CRP-mediated complement activation in vivo, which is based on the property that activated complement factors C3 and C4 fix to CRP during complement activation induced by this acute phase protein. We developed specific ELISAs for complexes between CRP and C4b, C4d, C3b, or C3d. We established that in vitro complement-CRP complexes were fo rmed only during CRP-dependent activation, and not during activation b y other activators, even in the presence of high CRP levels. Circulati ng levels of complement-CRP complexes were undetectable in normal dono rs, but significantly increased in nine patients following implantatio n of a renal allograft. Importantly, levels of complement-CRP complexe s did not change in these patients upon a bolus infusion of mAb OKT3, which induces activation of the classical complement pathway, demonstr ating in vivo that complement-CRP complexes are not formed during CRP- independent activation of complement, even when CRP is elevated. We co nclude that measurement of complement-CRP complexes provides a suitabl e tool to study CRP-mediated activation of complement in vivo. Further more, increased levels of these complexes occur in clinical samples, i ndicating that CRP may induce activation of complement in vivo.