Evidence map›Paper›PMID 29266033›Full record

ArticleTransplantation2018

Immune Responses of HLA Highly Sensitized and Nonsensitized Patients to Genetically Engineered Pig Cells.

Zhongqiang Zhang, Hidetaka Hara, Cassandra Long, Hayato Iwase, Haizhi Qi, Camila Macedo, Massimo Mangiola, Adriana Zeevi, Mohamed Ezzelarab, David Ayares and 2 more

Open access · greenAbstract readComparative Study
In one paragraph

Article in Transplantation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
4.0field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 31 citations in OpenAlex.

  1. Future of xenotransplantation in Korea.Clinical transplantation and research · 2026
    Review
  2. Article
  3. Pig Xenotransplantation in Beta Cell Replacement: Addressing Challenges and Harnessing Potential for Type 1 Diabetes Therapy.Transplant international : official journal of the European Society for Organ Transplantation · 2024
    Review
  4. Review
  5. Article
  6. Xenotransplantation: A New Era.Frontiers in immunology · 2022
    Review
  7. Review
  8. Porcine models of acute kidney injury.American journal of physiology. Renal physiology · 2021
    Article
  9. Clinical Pig Kidney Xenotransplantation: How Close Are We?Journal of the American Society of Nephrology : JASN · 2020
    Review
  10. Review
  11. Article
  12. Review
  13. Review
  14. Review
  15. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 2 countries.

Zhongqiang ZhangThomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA.
Hidetaka HaraThomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA.
Cassandra LongThomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA.
Hayato IwaseThomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA.
Haizhi QiDepartment of Organ Transplantation and General Surgery, Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
Camila MacedoThomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA.
Massimo MangiolaDepartment of Pathology, University of Pittsburgh, Pittsburgh, PA.
Adriana ZeeviDepartment of Pathology, University of Pittsburgh, Pittsburgh, PA.
Mohamed EzzelarabThomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA.
David AyaresRevivicor, Blacksburg, VA.
David K C CooperThomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA.
Martin WijkstromThomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA.
University of Pittsburgh · USSecond Xiangya Hospital of Central South University · CN

Funding

Prolonging life-supported pig kidney and heart graft survival in baboons by suppressing inflammationU19AI090959 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI COOPER, DAVID KC · 2010 to 2024
$26.3M
Thromboregulation to Prevent Thrombotic MicroangiopathyU01AI068642 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI COOPER, DAVID KC · 2005 to 2008
$2.7M
Tolerance to Carbohydrate Antigens in TransplantationR21AI074844 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI COOPER, DAVID KC · 2007 to 2008
$405k
NIAID NIH HHS R21 AI074844NIAID NIH HHS U01 AI068642NIAID NIH HHS U19 AI090959
6 · The paper itself

Abstract

backgroundWe investigated in vitro whether HLA highly sensitized patients with end-stage renal disease will be disadvantaged immunologically after a genetically engineered pig kidney transplant.

methodsBlood was drawn from patients with a calculated panel-reactive antibody (cPRA) 99% to 100% (Gp1, n = 10) or cPRA 0% (Gp2, n = 12), and from healthy volunteers (Gp3, n = 10). Serum IgM and IgG binding was measured (i) to galactose-α1-3 galactose and N-glycolylneuraminic acid glycans by enzyme-linked immunosorbent assay, and (ii) to pig red blood cell, pig aortic endothelial cells, and pig peripheral blood mononuclear cell from α1,3-galactosyltransferase gene-knockout (GTKO)/CD46 and GTKO/CD46/cytidine monophosphate-N-acetylneuraminic acid hydroxylase-knockout (CMAHKO) pigs by flow cytometry. (iii) T-cell and B-cell phenotypes were determined by flow cytometry, and (iv) proliferation of T-cell and B-cell carboxyfluorescein diacetate succinimidyl ester-mixed lymphocyte reaction.

results(i) By enzyme-linked immunosorbent assay, there was no difference in IgM or IgG binding to galactose-α1-3 galactose or N-glycolylneuraminic acid between Gps1 and 2, but binding was significantly reduced in both groups compared to Gp3. (ii) IgM and IgG binding in Gps1 and 2 was also significantly lower to GTKO/CD46 pig cells than in healthy controls, but there were no differences between the 3 groups in binding to GTKO/CD46/CMAHKO cells. (iii and iv) Gp1 patients had more memory T cells than Gp2, but there was no difference in T or B cell proliferation when stimulated by any pig cells. The proliferative responses in all 3 groups were weakest when stimulated by GTKO/CD46/CMAHKO pig peripheral blood mononuclear cell.

conclusions(i) End-stage renal disease was associated with low antipig antibody levels. (ii) Xenoreactivity decreased with increased genetic engineering of pig cells. (iii) High cPRA status had no significant effect on antibody binding or T-cell and B-cell response.

Indexed as

AnimalsAnimals, Genetically ModifiedB-LymphocytesCase-Control StudiesCells, CulturedGalactosyltransferasesGraft RejectionHeterograftsHLA AntigensHumansImmunologic MemoryIsoantibodiesKidney Failure, ChronicKidney TransplantationLymphocyte ActivationMembrane Cofactor Proteinalpha-1,3-galactosyltransferase 1, porcineCMPacetylneuraminate monooxygenaseGalactosyltransferasesHLA AntigensIsoantibodiesMembrane Cofactor ProteinMixed Function Oxygenases

Identifiers

PMID29266033
PMCPMC5924598
OpenAlexW2780547740

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.