- Poster presentation
- Open Access
Testing of anti-activated protein C antibodies in four drotrecogin alfa (activated) severe sepsis studies
© BioMed Central Ltd 2008
- Published: 13 March 2008
- Severe Sepsis
- Positive Sample
- Specific Immune Response
- Neutralize Activity
- Placebo Patient
This study evaluated anti-activated protein C (anti-APC) antibody (Ab) development in drotrecogin alfa (activated) (DAA) (recombinant human APC)-treated adult patients with severe sepsis.
Serum and plasma samples were collected for anti-APC Ab testing from patients in the PROWESS, EVBF (ENHANCE substudy), ADDRESS and XPRESS trials at baseline (BL) and on days 14, 28 and 60 (except PROWESS). PROWESS and ADDRESS were placebo-controlled studies. All patients in EVBF and XPRESS were DAA-treated. An ELISA detecting anti-APC IgA/IgG/IgM Abs (sensitivity: 0.26 μg/ml) was used to screen all serum samples from patients who had a BL sample and at least one post-BL sample. Confirmed positive samples (binding inhibited ≥ 50% with 50 μg/ml exogenous DAA) were titered by twofold serial dilutions. IgG isolated from plasma of positive samples was tested for neutralizing activity against DAA-induced prolongation of aPTT. Positive anti-APC Ab was analyzed on an 'as treated' basis.
The proportion of patients with anti-APC or neutralizing Ab was low and was similar between the 1,855 DAA patients and 1,493 placebo patients tested. No relationship between anti-APC Ab development and adverse reactions was observed. There was no evidence that the anti-APC Abs detected represented a specific immune response to DAA therapy.
This article is published under license to BioMed Central Ltd.