In vivo generation of C4d, Bb, iC3b, and SC5b-9 after OKT3 administration in kidney and lung transplant recipients

Details

Serval ID
serval:BIB_475FDE4B19A9
Type
Article: article from journal or magazin.
Collection
Publications
Title
In vivo generation of C4d, Bb, iC3b, and SC5b-9 after OKT3 administration in kidney and lung transplant recipients
Journal
Transplantation
Author(s)
Vallhonrat  H., Williams  W. W., Cosimi  A. B., Tolkoff-Rubin  N., Ginns  L. C., Wain  J. C., Preffer  F., Olszak  I., Wee  S., Delmonico  F. L., Pascual  M.
ISSN
0041-1337
Publication state
Published
Issued date
01/1999
Peer-reviewed
Oui
Volume
67
Number
2
Pages
253-8
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jan 27
Abstract
BACKGROUND: OKT3 monoclonal antibody therapy results in an acute clinical syndrome (ACS) associated with the release of tumor necrosis factor and sequestration of neutrophils in the lungs. We have previously shown that inhibition of tumor necrosis factor does not completely eliminate OKT3-ACS, suggesting that other factors also contribute to the ACS. The current studies analyzed complement activation in vivo during the first hour after OKT3 administration. METHODS: Renal (n=4) and lung (n=4) transplant recipients received OKT3 as treatment for rejection and induction therapy, respectively. Complement activation products C4d, Bb, iC3b, and SC5b-9 were measured by ELISA. Hemodynamic parameters were also monitored in the lung transplant recipients. Neutrophil expression of CD11a, CD11b, and CD18 was monitored by flow cytometry. Controls included patients receiving methylprednisolone for rejection (n=4), two adults with adult respiratory distress syndrome who received extracorporeal membrane oxygenation, and normal volunteers (n=5). P values less than 0.05 (*) were considered significant. RESULTS: Increases in the plasma levels of C4d, Bb, iC3b, and SC5b-9 were observed in seven of eight patients after OKT3 administration. Mean values (n=8) at 0, 15, and 60 min (in microg/ml) were as follows-C4d: 1.865, 2.644*, and 2.607*; Bb: 0.245, 0.411, and 0.385; iC3b: 10.881, 17.242*, and 15.145*; and SC5b-9: 0.232, 0.269, and 0.302*. An increase in CD11b and CD18 and a decrease of CD11a on neutrophils in parallel with complement activation was observed. In lung transplant recipients, C3 activation correlated with increases in mean pulmonary and central venous pressures (P<0.05). As compared with extracorporeal membrane oxygenation, which activated classical and alternative pathways, OKT3 predominantly activated complement by the classical pathway. Methylprednisolone pulses did not activate complement. CONCLUSIONS: Complement activation is an early event after OKT3 administration and is associated with the increased expression of adhesion molecules on neutrophils and with pulmonary hemodynamic changes. Effective therapeutic approaches to the control of early monoclonal antibody side effects may require measures that limit complement activation in addition to reducing cytokine activity.
Keywords
Adult Aged Blood Pressure Complement Activation Complement C3 Convertase, Alternative Pathway Complement C3b/*biosynthesis Complement C4/*biosynthesis *Complement C4b Complement Membrane Attack Complex/*biosynthesis Enzyme-Linked Immunosorbent Assay Female Heart Rate *Hemodynamics Humans Immunosuppressive Agents/*therapeutic use Kidney Transplantation/*immunology/physiology Lung Transplantation/*immunology/physiology Male Methylprednisolone/therapeutic use Middle Aged Models, Chemical Muromonab-CD3/*therapeutic use Peptide Fragments/*biosynthesis
Pubmed
Web of science
Create date
29/01/2008 13:52
Last modification date
20/08/2019 13:53
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