PMID- 10075589
OWN - NLM
STAT- MEDLINE
DCOM- 19990311
LR  - 20190713
IS  - 0041-1337 (Print)
IS  - 0041-1337 (Linking)
VI  - 67
IP  - 2
DP  - 1999 Jan 27
TI  - In vivo generation of C4d, Bb, iC3b, and SC5b-9 after OKT3 administration in 
      kidney and lung transplant recipients.
PG  - 253-8
AB  - 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.
FAU - Vallhonrat, H
AU  - Vallhonrat H
AD  - Massachusetts General Hospital, and Department of Surgery, Harvard Medical 
      School, Boston 02114, USA.
FAU - Williams, W W
AU  - Williams WW
FAU - Cosimi, A B
AU  - Cosimi AB
FAU - Tolkoff-Rubin, N
AU  - Tolkoff-Rubin N
FAU - Ginns, L C
AU  - Ginns LC
FAU - Wain, J C
AU  - Wain JC
FAU - Preffer, F
AU  - Preffer F
FAU - Olszak, I
AU  - Olszak I
FAU - Wee, S
AU  - Wee S
FAU - Delmonico, F L
AU  - Delmonico FL
FAU - Pascual, M
AU  - Pascual M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (Complement C4)
RN  - 0 (Complement Membrane Attack Complex)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Muromonab-CD3)
RN  - 0 (Peptide Fragments)
RN  - 80295-43-8 (Complement C3b)
RN  - 80295-50-7 (Complement C4b)
RN  - 80295-52-9 (complement C4d)
RN  - EC 3.4.21.47 (Complement C3 Convertase, Alternative Pathway)
RN  - X4W7ZR7023 (Methylprednisolone)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Blood Pressure
MH  - Complement Activation
MH  - Complement C3 Convertase, Alternative Pathway
MH  - Complement C3b/*biosynthesis
MH  - Complement C4/*biosynthesis
MH  - *Complement C4b
MH  - Complement Membrane Attack Complex/*biosynthesis
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Heart Rate
MH  - *Hemodynamics
MH  - Humans
MH  - Immunosuppressive Agents/*therapeutic use
MH  - Kidney Transplantation/*immunology/physiology
MH  - Lung Transplantation/*immunology/physiology
MH  - Male
MH  - Methylprednisolone/therapeutic use
MH  - Middle Aged
MH  - Models, Chemical
MH  - Muromonab-CD3/*therapeutic use
MH  - Peptide Fragments/*biosynthesis
EDAT- 1999/02/12 00:00
MHDA- 1999/02/12 00:01
CRDT- 1999/02/12 00:00
PHST- 1999/02/12 00:00 [pubmed]
PHST- 1999/02/12 00:01 [medline]
PHST- 1999/02/12 00:00 [entrez]
AID - 10.1097/00007890-199901270-00011 [doi]
PST - ppublish
SO  - Transplantation. 1999 Jan 27;67(2):253-8. doi: 10.1097/00007890-199901270-00011.