Evidence against a pivotal role of preformed antibodies in delayed rejection of a guinea pig–to–rat heart xenograft  Helmut Grimm, MD, PhDa, Petra Mages,

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Presentation on theme: "Evidence against a pivotal role of preformed antibodies in delayed rejection of a guinea pig–to–rat heart xenograft  Helmut Grimm, MD, PhDa, Petra Mages,"— Presentation transcript:

1 Evidence against a pivotal role of preformed antibodies in delayed rejection of a guinea pig–to–rat heart xenograft  Helmut Grimm, MD, PhDa, Petra Mages, MDa, Gertraut Lindemann, MDa, Mechthild Potthoff, MDa, Ulrich Bohnet, MDa, Stephan Korom, MDa, Leander Ermert, MDb  The Journal of Thoracic and Cardiovascular Surgery  Volume 119, Issue 3, Pages (March 2000) DOI: /S (00) Copyright © 2000 Mosby, Inc. Terms and Conditions

2 Fig. 1 Kinetics of natural antibody (A) , total IgM (B) , and total IgG levels (C) after plasmapheresis in rats. Values shown are means ± SD of 6 independent experiments. SD bars are missing when interfering with or falling into symbol. Arrows mark the end of plasmapheresis. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /S (00) ) Copyright © 2000 Mosby, Inc. Terms and Conditions

3 Fig. 2 Kinetics of complement activity (C’H 50) after plasmapheresis in rats. Values are shown as means ± SD of 6 independent experiments. SD bars are missing when interfering with or falling into symbol. Arrow marks the end of plasmapheresis. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /S (00) ) Copyright © 2000 Mosby, Inc. Terms and Conditions

4 Fig. 3 TNF-α secretory potential on stimulation with various amounts of concanavalin A (Con A) of PBMCs harvested from rats (n = 6 for each group) immediately or 2 days after plasmapheresis (PP) . Values are given as means ± SD. SD bars are missing when interfering with or falling into symbol. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /S (00) ) Copyright © 2000 Mosby, Inc. Terms and Conditions

5 Fig. 4 Proliferative response on stimulation with syngeneic rat lymphocytes (negative control), xenogeneic guinea pig lymphocytes, and concanavalin A (positive control) of lymphocytes harvested from rats (n = 6 for each group) before (A) , immediately after (B), and 2 days after (C) plasmapheresis, as measured by immunoenzymatic reactivity for bromodeoxyuridine incorporation (optical density [o.d.] at 492 nm wave length). *P > .2 among the different therapeutic groups; #P > .2 within a given group. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /S (00) ) Copyright © 2000 Mosby, Inc. Terms and Conditions

6 Fig. 5 Graphic representation of the different xenotransplantation settings in relation to the kinetics of preformed xenoantibodies (filled circles) and complement activity (plus signs) , as determined in preliminary studies. The arrow (Tx) marks the time point when xenotransplantation was drafted without plasmapheresis (A) (unmodified preformed xenoantibody level), immediately after plasmapheresis (B) (reduced preformed xenoantibodies), or 2 days after plasmapheresis (C) (rebounding preformed xenoantibodies) and in combination with complement inactivation by CVF (A′, unmodified preformed xenoantibody level with the complement inactivated; B′, reduced preformed xenoantibodies with the complement inactivated; C′, rebounding preformed xenoantibodies with the complement inactivated). Values on the right side of the arrow actually do not represent measurements after xenografting but characterize the kinetics as they occur in the different therapeutic settings without transplantation. For reasons of clarity, SDs, which can be depicted from Figs 1 and 2, are not presented. Values are given in relation to the starting point, which is set at 1.0. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /S (00) ) Copyright © 2000 Mosby, Inc. Terms and Conditions

7 Fig. 6 Photomicrographs of immunophosphatase labeling of guinea pig cardiac xenografts from decomplemented rats treated with plasmapheresis immediately before (A) or 2 days before (B) transplantation. TNF-α labeling of cryostat sections (original magnification, ×400) is distinctly diminished in B compared with A . The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /S (00) ) Copyright © 2000 Mosby, Inc. Terms and Conditions

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