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Right arrow Lung - transplantation

Ann Thorac Surg 2001;72:1681-1690
© 2001 The Society of Thoracic Surgeons

Original article: general thoracic

Role of anti-Gal{alpha}1,3Gal and anti–platelet antibodies in hyperacute rejection of pig lung by human blood

Steffen Pfeiffer, MDa, George L. Zorn, III, MDa, Sean Kelishadi, BSa, Rafael Oriol, MDb, Philippe Wolf, MDc, Richard N. Pierson, III, MDa, Agnes M. Azimzadeh, PhD*a

a Department of Cardiac and Thoracic Surgery, Vanderbilt University Medical Center and VA Medical Center, Nashville, Tennessee, USA
b Inserm U504, Cell Glycobiology and Signaling, Villejuif, France
c Department of Transplantation Surgery, Centre Hospital Universitaire, Strasbourg, France

* Address reprint requests to Dr Azimzadeh, Department of Cardiac and Thoracic Surgery, 2986 The Vanderbilt Clinic, Nashville, TN 37232-5734, USA
e-mail: agnes.azimzadeh{at}mcmail.vanderbilt.edu

Presented at the Thirty-seventh Annual Meeting of The Society of Thoracic Surgeons, New Orleans, LA, Jan 29–31, 2001.

Background. Previous work has shown that antibodies against porcine antigens are an important trigger of hyperacute lung rejection (HALR). The relative importance of Gal{alpha}1,3Gal epitopes and other antigens, such as those expressed on pig platelet membranes or lung itself, has not been defined. This study compares the efficiency of three anti–pig antibody depletion strategies, and their efficacy with regard to attenuation of HALR.

Methods. Plasma pooled from three human donors was adsorbed against Gal{alpha}1,3Gal disaccharide or porcine platelet extract (PPE), or passed through pig lung vasculature. Whole blood reconstituted using adsorbed plasma was then used to perfuse piglet lung, and results were compared with unmodified human blood.

Results. Depletion of lung-reactive anti–Gal{alpha}1-3Gal antibodies was most efficient with the {alpha}Gal column (99% ± 0.5% vs 87% to 93% ± 11% for PPE and 92% to 95% ± 8% for lung, p < 0.01 vs {alpha}Gal column). PPE column tended to be more efficient (77% to 84% ± 12%) in removing anti-PPE antibodies than pig lung (66% to 70% ± 14%) or the {alpha}Gal column (56% to 63% ± 16%, p < 0.05). Lung survival and function with each antibody depletion strategy was improved relative to unmodified controls (mean survival >=146 minutes vs 8 minutes for controls). Although {alpha}Gal and lung adsorption yielded more consistent lung protection (survival beyond 2 hours) than did PPE, no approach proved significantly superior. Complement C3a elaboration at 10 minutes was attenuated >80% by each adsorption strategy, an effect that was most pronounced in the lung adsorption group (95%, p < 0.01). Histamine elaboration was blunted significantly by PPE adsorption but not in other groups (p < 0.05). Platelet but not leukocyte sequestration was decreased with antibody depletion compared with the nondepleted group (44% to 50% vs 82%, p < 0.01).

Conclusions. Each antibody depletion strategy tested significantly prolongs lung xenograft survival and function compared with unmodified human blood, but none was sufficient to reliably prevent HALR. Depletion of antibodies against both {alpha}Gal and additional cell membrane antigens, or control of antibody-independent pathogenic pathways, may be necessary to consistently prevent HALR.






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