An investigation of the specificity of induced anti-pig antibodies in baboons.

Abstract:

AIM:To provide information on the specificity of induced anti-pig antibodies (Abs) in baboons after exposure and sensitization to pig antigens. MATERIALS AND METHODS:Baboons (n=7) received either porcine mobilized peripheral blood progenitor cells (n=3), kidney (n=3) or heart (n=1) transplants. After rejection of these cells or organs, pre- and post-rejection sera were analyzed by enzyme-linked immunosorbent assay (ELISA) and flow cytometry to detect and measure anti-Galactosealpha1,3Galactose (Gal) and anti-non-Gal Abs. To study the anti-non-Gal carbohydrate response, the sera were incubated with pig red blood cells pretreated with alpha-galactosidase (to remove Gal) and three other exoglycosidases to remove other potential oligosaccharide epitopes, and studied by flow cytometry. To study the anti-swine leukocyte antigen (SLA) response, non-Gal Abs from two baboons sensitized with kidneys from inbred miniature swine of dd or aa haplotype, respectively, were adsorbed on cells of aa, cc, or dd haplotypes, and binding to aa, cc or dd cells was measured by flow cytometry. Cytotoxicity of anti-non-Gal Abs was tested in vitro by a complement-mediated cytotoxicity assay, using pig cells as targets. RESULTS:In pre-transplant and pre-rejection sera, anti-Gal Abs were detected, but anti-non-Gal Abs were either absent or at minimal levels. After exposure to pig antigens, baboons developed induced anti-Gal and anti-non-Gal Abs. No anti-non-Gal Abs directed to the tested carbohydrate epitopes could be detected. Anti-non-Gal Abs showed minor evidence of specific SLA haplotype reactivity, suggesting that the major Ab response was to pan-pig determinants. Anti-non-Gal Abs showed a low level of complement-mediated lysis of pig cells in vitro. CONCLUSIONS:In this limited study, no Ab response to non-Gal carbohydrates was observed, and anti-SLA specificity was minor, indicating that most induced anti-non-Gal Ab was directed against non-specific pig proteins, including SLA-epitopes.

journal_name

Xenotransplantation

journal_title

Xenotransplantation

authors

Buhler L,Xu Y,Li W,Zhu A,Cooper DK

doi

10.1034/j.1399-3089.2003.01122.x

subject

Has Abstract

pub_date

2003-01-01 00:00:00

pages

88-93

issue

1

eissn

0908-665X

issn

1399-3089

pii

1o122

journal_volume

10

pub_type

杂志文章
  • Improved osseointegration using porcine xenograft compared to demineralized bone matrix for the treatment of critical defects in a small animal model.

    abstract:BACKGROUND:Autograft (AG) is the gold standard bone graft due to biocompatibility, osteoconductivity, osteogenicity, and osteoinductivity. Alternatives include allografts and xenografts (XG). METHODS:We investigated the osseointegration and biocompatibility of a decellularized porcine XG within a critical defect anima...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/xen.12662

    authors: Jinnah AH,Whitlock P,Willey JS,Danelson K,Kerr BA,Hassan OA,Emory CL,Smith TL,Bracey DN

    更新日期:2020-11-26 00:00:00

  • Presence of Gal-alpha1,3Gal epitope on xenogeneic lines: implications for cellular gene therapy based on the encapsulation technology.

    abstract::Exposure to human serum induces the lysis of xenogeneic cells through natural antibodies and complement activation. The carbohydrate Galactose-alpha1,3-Galactose (Gal-alpha1,3-Gal) epitope, has been shown to be the principal antigenic determinant on target cells. This reaction is, therefore, particularly important for...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1034/j.1399-3089.2003.00110.x

    authors: Déglon N,Aubert V,Spertini F,Winkel L,Aebischer P

    更新日期:2003-05-01 00:00:00

  • Anti-Gal antibody-mediated skin graft rejection requires a threshold level of Gal expression.

    abstract:BACKGROUND:Despite overcoming xenograft hyperacute rejection (HAR), Gal (galactose-alpha1,3-galactose) expression may not be completely eliminated from the alpha1,3-galactosyltransferase gene knockout (Gal KO) pig because of alternative galactosyltransferases. Whether low levels of "residual" Gal are still susceptible ...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/j.1399-3089.2007.00437.x

    authors: Murray-Segal L,Gock H,Cowan PJ,d'Apice AJ

    更新日期:2008-02-01 00:00:00

  • Species incompatibilities in the pig-to-macaque islet xenotransplant model affect transplant outcome: a comparison with allotransplantation.

    abstract:BACKGROUND:Porcine islet transplantation into diabetic non-human primates is considered most relevant in translational research supporting a clinical application. Most studies have focused on immunosuppressive protocols, while metabolic aspects have mainly been utilized in graft monitoring. We evaluated data from our g...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/j.1399-3089.2011.00676.x

    authors: Graham ML,Bellin MD,Papas KK,Hering BJ,Schuurman HJ

    更新日期:2011-11-01 00:00:00

  • Regulation of xenogeneic porcine pancreatic islets.

    abstract::The use of xenogeneic porcine pancreatic islets has been shown to be a potentially promising alternative to using human allogeneic islets to treat insulin-dependent type 1 diabetes (T1D). This article provides an overview of the existing FDA regulatory framework that would be applied to the regulation of clinical tria...

    journal_title:Xenotransplantation

    pub_type: 杂志文章,评审

    doi:10.1111/j.1399-3089.2010.00592.x

    authors: Arcidiacono JA,Evdokimov E,Lee MH,Jones J,Rudenko L,Schneider B,Snoy PJ,Wei CH,Wensky AK,Wonnacott K

    更新日期:2010-09-01 00:00:00

  • Increased human tumor necrosis factor-α levels induce procoagulant change in porcine endothelial cells in vitro.

    abstract:BACKGROUND:Intravascular thrombosis and systemic coagulation abnormalities are major hurdles to successful xenotransplantation and are signs of acute humoral rejection. Increased expression of tissue factor (TF) is associated with the development of microvascular thrombosis in xenografts. To develop an effective strate...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/j.1399-3089.2012.00704.x

    authors: Lee KG,Lee H,Ha JM,Lee YK,Kang HJ,Park CG,Kim SJ

    更新日期:2012-05-01 00:00:00

  • Epigenetic biomarkers indicate islet cell death in xenotransplantation.

    abstract:BACKGROUND:Xenotransplantation of porcine islets has emerged in recent decades as a potential treatment for type 1 diabetes (T1D). Current methods of detection, indicative of successful engraftment, occur downstream of actual islet death. Epigenetic biomarkers can be detected in circulating cell-free DNA (cfDNA) to pro...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/xen.12570

    authors: Faulk C,Mueller KR,Cheishvili D,Colwell M,Pepin AS,Syzf M,Hering BJ,Burlak C

    更新日期:2020-03-01 00:00:00

  • Rat-to-mouse small bowel xenotransplantation: a novel model for studying acute vascular and hyperacute xenograft rejection and xenogenic cell migration.

    abstract::The present study was undertaken to establish a rat-to-mouse vascularized small bowel xenotransplantation model to study acute vascular and hyperacute xenograft rejection, and xenogenic cell migration. Lewis rat small bowel grafts were transplanted heterotopically to group 1, Balb/c mice, and group 2, Balb/c mice pre-...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1034/j.1399-3089.1999.00001.x

    authors: Kiyochi H,Kellersmann R,Blömer A,Garcia BM,Zhang Z,Zhong R,Grant DR

    更新日期:1999-02-01 00:00:00

  • Semi-xenotransplantation: the regenerative medicine-based approach to immunosuppression-free transplantation and to meet the organ demand.

    abstract::Although xenografts have always held immeasurable potential as an inexhaustible source of donor organs, immunological barriers and physiological incompatibility have proved to be formidable obstacles to clinical utility. An exciting, new regenerative medicine-based approach termed "semi-xenotransplantation" (SX) seeks...

    journal_title:Xenotransplantation

    pub_type: 杂志文章,评审

    doi:10.1111/xen.12122

    authors: Salvatori M,Peloso A,Katari R,Soker S,Lerut JP,Stratta RJ,Orlando G

    更新日期:2015-01-01 00:00:00

  • Heart transplantation across antibodies against human leukocyte antigen and ABO-post-transplant follow-up of donor reactive antibodies.

    abstract:BACKGROUND:We have successfully performed heart transplantation despite the most unfavourable risk factors for graft and patient survival: the presence of a high level of antibodies (Abs) against the donor's human leukocyte antigens (HLA) class I/II and blood group A1 antigens. The present study concerns post-transplan...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/j.1399-3089.2006.00276.x

    authors: Bućin D,Johansson S,Lindberg LO

    更新日期:2006-03-01 00:00:00

  • Role of anti-CD40 antibody-mediated costimulation blockade on non-Gal antibody production and heterotopic cardiac xenograft survival in a GTKO.hCD46Tg pig-to-baboon model.

    abstract:BACKGROUND:Recently, we have shown that an immunosuppression regimen including costimulation blockade via anti-CD154 antibody significantly prolongs the cardiac xenograft survival in a GTKO.hCD46Tg pig-to-baboon heterotopic xenotransplantation model. Unfortunately, many coagulation disorders were observed with the use ...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/xen.12066

    authors: Mohiuddin MM,Singh AK,Corcoran PC,Hoyt RF,Thomas ML 3rd,Lewis BG,Eckhaus M,Dabkowski NL,Belli AJ,Reimann KA,Ayares D,Horvath KA

    更新日期:2014-01-01 00:00:00

  • T-cell responses during pig-to-primate xenotransplantation.

    abstract:UNLABELLED:Xenotransplantation using porcine organs may resolve a chronic shortage of donor organs for clinical transplantation if significant immunological barriers can be overcome. To determine the potential role of T lymphocytes in Xenograft (Xg) rejection, we transplanted transgenic hCD46 porcine hearts heterotopic...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/j.1399-3089.2005.00258.x

    authors: Davila E,Byrne GW,LaBreche PT,McGregor HC,Schwab AK,Davies WR,Rao VP,Oi K,Tazelaar HD,Logan JS,McGregor CG

    更新日期:2006-01-01 00:00:00

  • Thromboelastographic evaluation of coagulative profiles in pig-to-monkey kidney xenotransplantation.

    abstract:BACKGROUND:Activation of the clotting cascade is central in acute xenograft rejection (AHXR) that occurs when pig organs are transplanted into primates. The coagulopathy reported in this model is a very complex process that involves simultaneously coagulation factors, platelets and phospholipid-bearing cells (i.e., leu...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/xen.12024

    authors: Spiezia L,Boldrin M,Radu C,Bulato C,Bertini D,Bon M,Campello E,Vadori M,Galli C,Gavasso S,Nottle MB,Cowan PJ,Cozzi E,Simioni P

    更新日期:2013-03-01 00:00:00

  • Pig peripheral blood mononuclear cells are directly associated with the thrombotic microangiopathy that complicates the induction of chimerism in pig-to-baboon xenotransplantation.

    abstract::The infusion of large numbers of porcine cells into primates in order to induce specific immunologic tolerance by mixed hematopoietic chimerism, results in thrombotic microangiopathy that can be fatal. For this reason, it is important to study in vitro the interaction of primate endothelial cells with pig cells. We sh...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1034/j.1399-3089.2002.01066.x

    authors: Benatuil L,Fernandez AZ,Apitz-Castro R,Romano E

    更新日期:2002-05-01 00:00:00

  • Effect of cell surface concentration of human DAF on transgenic pig aortic endothelial cells on the degree of protection afforded against human complement deposition.

    abstract::Cultures of hDAF transgenic porcine aortic endothelial cells (TPAEs) with levels of cell surface hDAF expression between 2000 and 300 000 molecules per cell have been used to determine the relationship between expression of hDAF and protection from human complement deposition in an in vitro model. At concentrations be...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1034/j.1399-3089.2001.00086.x

    authors: Carrington CA,dos Santos Cruz G

    更新日期:2001-05-01 00:00:00

  • Financial aspects of organ procurement from deceased donors in the USA-Relevance to xenotransplantation.

    abstract::When clinical xenotransplantation is introduced, the costs associated with acquisition of a genetically engineered pig organ are as yet unknown. How will these costs compare with those currently associated with the acquisition of deceased human organs? An understanding of the financial aspects of deceased organ and ti...

    journal_title:Xenotransplantation

    pub_type: 杂志文章,评审

    doi:10.1111/xen.12322

    authors: Saari RJ,Cooper DKC

    更新日期:2017-07-01 00:00:00

  • Acceptance of organ xenotransplantation among Latin American immigrants resident in the United States.

    abstract:BACKGROUND:Making xenotransplantation socially acceptable is the first step in working toward the promotion of this potential therapy option for providing transplant organs. OBJECTIVE:To analyze the attitude toward xenotransplantation among the Latin American population resident in Florida (the USA), and to determine ...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/xen.12250

    authors: Ríos A,López-Navas AI,Martínez-Alarcón L,Ramis G,Hernández AM,Ayala MA,Garrido G,Ramírez P,Parrilla P

    更新日期:2016-07-01 00:00:00

  • Identification of soluble and membrane-bound isoforms of porcine tumor necrosis factor receptor 2.

    abstract:BACKGROUND:TNF and its receptors TNF-Receptor 1 (TNFR1, CD120a) and TNF-Receptor 2 (TNFR2, CD120b) have been implicated in the rejection of transplanted cells and organs. Although pig TNFR1 (pTNFR1) is known to mediate the effects of human TNF in a xenogeneic setting, it is unclear whether pig TNFR2 (pTNFR2) could cont...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/j.1399-3089.2011.00634.x

    authors: Uribe-Herranz M,Casinghino SR,Bosch-Presegué L,Fodor WL,Costa C

    更新日期:2011-03-01 00:00:00

  • First update of the International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes--Chapter 6: patient selection for pilot clinical trials of islet xenotransplan

    abstract::Patients in whom type 1 diabetes is complicated by impaired awareness of hypoglycemia and recurrent episodes of severe hypoglycemia are candidates for islet or pancreas transplantation if severe hypoglycemia persists after completion of a structured stepped care approach or a formalized medical optimization run-in per...

    journal_title:Xenotransplantation

    pub_type: 共识发展会议,杂志文章

    doi:10.1111/xen.12228

    authors: Hering BJ,O'Connell PJ

    更新日期:2016-01-01 00:00:00

  • Cytokine-inducible promoters to drive dynamic transgene expression: The "Smart Graft" strategy.

    abstract:BACKGROUND:Ubiquitous expression of T-cell regulatory transgenes such as the cytotoxic T lymphocyte-associated antigen 4 (CTLA4) or the high-affinity variant LEA29Y improves xeno graft survival. Such donor pigs are however immunocompromised and susceptible to infection. Continous high expression of CTLA4 or LEA29Y in t...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/xen.12634

    authors: Fischer A,Manske K,Seissler J,Wohlleber D,Simm N,Wolf-van Buerck L,Knolle P,Schnieke A,Fischer K

    更新日期:2020-11-01 00:00:00

  • ABO-incompatible live donor renal transplantation using blood group A/B carbohydrate antigen immunoadsorption and anti-CD20 antibody treatment.

    abstract:BACKGROUND:Blood group ABO-incompatible live donor (LD) renal transplantation may provide a significant source of organs. We report the results of our first 14 cases of ABO-incompatible LD renal transplantation using specific anti-A/B antibody (Ab) immunoadsorption (IA) and anti-CD20 monoclonal Ab (mAb) treatment. PATI...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/j.1399-3089.2006.00280.x

    authors: Nordén G,Briggs D,Cockwell P,Lipkin G,Mjörnstedt L,Mölne J,Ready A,Rydberg L,Samuelsson O,Svalander CT,Breimer ME

    更新日期:2006-03-01 00:00:00

  • Intragraft cytokine mRNA expression in rejecting and non-rejecting vascularized xenografts.

    abstract:BACKGROUND:The aim of the present study was to further investigate the characteristics of both graft-infiltrating cells and splenocytes during acute vascular rejection (AVR), cell-mediated rejection and non-rejection of vascularized concordant xenografts, by analysing both proinflammatory [interleukin-1beta (IL-1beta) ...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1034/j.1399-3089.2003.02032.x

    authors: Lorant T,Krook H,Wilton J,Olausson M,Tufveson G,Korsgren O,Johnsson C

    更新日期:2003-07-01 00:00:00

  • Systemic immune modulation using chemokine receptor 7 expressing porcine Sertoli cells.

    abstract:BACKGROUND:Sertoli cells (SC) are known to have active mechanism for evading humoral immune response and are known to have immune modulatory effects in the presence of other antigens. This has led us to hypothesize that systemic immune modulating effect of SC might be optimized by their residence on peripheral lymph no...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/j.1399-3089.2007.00435.x

    authors: Lee HM,Lim HG,Oh BC,Park CS,Lee DS,Lee JR

    更新日期:2007-11-01 00:00:00

  • Evaluation of isolated caprine pancreatic islets cytoarchitecture by laser scanning confocal microscopy and flow cytometry.

    abstract:BACKGROUND:Pancreatic islets are composed of different hormone-secreting cell types. A finely balanced combination of endocrine cells in the islets regulates intraportal vein secretions and plasma nutrient levels. Every islet cell type is distinguished by its specific secretory granule pattern and hormone content, endo...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/xen.12220

    authors: Hani H,Nazariah Allaudin Z,Mohd-Lila MA,Sarsaifi K,Tengku-Ibrahim TA,Mazni Othman A

    更新日期:2016-03-01 00:00:00

  • Circulating pig-specific DNA as a novel biomarker for monitoring xenograft rejection.

    abstract::Monitoring for immune rejection is crucial for long-term survival of pig xenografts. Circulating DNA is a promising non-invasive biomarker for either organ injury or response to therapy. In this study, circulating pig-specific DNA (cpsDNA) was monitored during xenograft rejection. Potential targets of cpsDNA were sele...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/xen.12522

    authors: Zhou M,Lu Y,Zhao C,Zhang J,Cooper DKC,Xie C,Song Z,Gao H,Qu Z,Lin S,Deng Y,Hara H,Zhan Y,Jiang Z,Dai Y,Wu C,Cai Z,Mou L

    更新日期:2019-07-01 00:00:00

  • Diabetes induction by total pancreatectomy in minipigs with simultaneous splenectomy: a feasible approach for advanced diabetes research.

    abstract:BACKGROUND:Safe and reliable diabetes models are a key prerequisite for advanced preclinical studies on diabetes. Chemical induction is the standard model of diabetes in rodents and also widely used in large animal models of non-human primates and minipigs. However, uncertain efficacy, the potential of beta-cell regene...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/xen.12255

    authors: Heinke S,Ludwig B,Schubert U,Schmid J,Kiss T,Steffen A,Bornstein S,Ludwig S

    更新日期:2016-09-01 00:00:00

  • The usefulness and limitations of the diabetic macaque model in evaluating long-term porcine islet xenograft survival.

    abstract:BACKGROUND:  Various groups have reported prolonged diabetes reversal and graft function after porcine islet transplantation into diabetic macaques using different experimental designs (macaque source, islet source, type of immunosuppression): subsequently, the International Xenotransplantation Association has publishe...

    journal_title:Xenotransplantation

    pub_type: 杂志文章,评审

    doi:10.1111/xen.12012

    authors: Graham ML,Schuurman HJ

    更新日期:2013-01-01 00:00:00

  • Donor-derived infections and infectious risk in xenotransplantation and allotransplantation.

    abstract::Post-transplantation infections are common in allograft recipients and should be expected in all immunocompromised hosts. Based on the need for immunosuppression in xenotransplantation, procedures developed to enhance safety in allotransplantation can be applied in future xenotransplantation clinical trials. Standardi...

    journal_title:Xenotransplantation

    pub_type: 杂志文章,评审

    doi:10.1111/xen.12423

    authors: Nellore A,Fishman JA

    更新日期:2018-07-01 00:00:00

  • Toward a solution for cardiac failure in the newborn.

    abstract::The newborn infant with severe cardiac failure owed to congenital structural heart disease or cardiomyopathy poses a daunting therapeutic challenge. The ideal solution for both might be cardiac transplantation if availability of hearts was not limiting and if tolerance could be induced, obviating toxicity of immunosup...

    journal_title:Xenotransplantation

    pub_type: 杂志文章,评审

    doi:10.1111/xen.12479

    authors: Platt JL,West LJ,Chinnock RE,Cascalho M

    更新日期:2018-11-01 00:00:00

  • Pre-clinical heterotopic intrathoracic heart xenotransplantation: a possibly useful clinical technique.

    abstract:BACKGROUND:As a step towards clinical cardiac xenotransplantation, our experimental heterotopic intrathoracic xenotransplantation model offers a beating and ejecting donor heart while retaining the recipient's native organ as a backup in case of graft failure. Clinically applicable immunosuppressive regimens (IS) were ...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/xen.12213

    authors: Abicht JM,Mayr T,Reichart B,Buchholz S,Werner F,Lutzmann I,Schmoeckel M,Bauer A,Thormann M,Langenmayer M,Herbach N,Pohla H,Herzog R,McGregor CG,Ayares D,Wolf E,Klymiuk N,Baehr A,Kind A,Hagl C,Ganswindt U,Belka C

    更新日期:2015-11-01 00:00:00