Evidence map›Paper›PMID 27888551›Full record

ArticleAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons2017

Selective Targeting of High-Affinity LFA-1 Does Not Augment Costimulation Blockade in a Nonhuman Primate Renal Transplantation Model.

K P Samy, D J Anderson, D J Lo, M S Mulvihill, M Song, A B Farris, B S Parker, A L MacDonald, C Lu, T A Springer and 8 more

Open access · bronzeAbstract read
In one paragraph

Article in American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

5 citing papers in PubMed, 9 citations in OpenAlex.

  1. Endogenous memory T cells with donor-reactivity: early post-transplant mediators of acute graft injury in unsensitized recipients.Transplant international : official journal of the European Society for Organ Transplantation · 2021
    Review
  2. Secondary lymphoid tissue and costimulation-blockade resistant rejection: A nonhuman primate renal transplant study.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2019
    Article
  3. Review
  4. Article
  5. 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

18 authors at 6 institutions in 1 country.

K P SamyDepartment of Surgery, Duke University School of Medicine, Durham, NC.
D J AndersonEmory Transplant Center, Emory University School of Medicine, Atlanta, GA.
D J LoEmory Transplant Center, Emory University School of Medicine, Atlanta, GA.
M S MulvihillDepartment of Surgery, Duke University School of Medicine, Durham, NC.
M SongDepartment of Surgery, Duke University School of Medicine, Durham, NC.
A B FarrisDepartment of Pathology & Laboratory Medicine, Emory University School of Medicine, Atlanta, GA.
B S ParkerDepartment of Surgery, Duke University School of Medicine, Durham, NC.
A L MacDonaldDepartment of Surgery, Duke University School of Medicine, Durham, NC.
C LuProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA.
T A SpringerProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA.
S C KachlanySchool of Medicine, Rutgers University, Newark, NJ.
K A ReimannMass-Biologics, University of Massachusetts Medical School, Boston, MA.
T HowDepartment of Surgery, Duke University School of Medicine, Durham, NC.
F V LeopardiDepartment of Surgery, Duke University School of Medicine, Durham, NC.
K S FrankeDivision of Laboratory Animal Resources, Duke University, Durham, NC.
K D WilliamsDivision of Laboratory Animal Resources, Duke University, Durham, NC.
B H CollinsDepartment of Surgery, Duke University School of Medicine, Durham, NC.
A D KirkDepartment of Surgery, Duke University School of Medicine, Durham, NC.
Duke University · USEmory University · USBoston Children's Hospital · USHarvard University · USRutgers, The State University of New Jersey · USUniversity of Massachusetts Chan Medical School · US

Funding

Transplant Tolerance in Non-Human PrimatesU19AI051731 · NIAID · UNIVERSITY OF WESTERN ONTARIO · PI LARSEN, CHRISTIAN P. · 2002 to 2022
$54.1M
Nonhuman Primate Reagent ResourceU24AI126683 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Diogo Magnani · 2016 to 2026
$20.1M
Resource for Nonhuman Primate Cell Depleting AntibodiesR24OD010976 · OD · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI ENGELMAN, KATHLEEN, MAGNANI, DIOGO · 2012 to 2019
$4.7M
T Cell Maturation and the Nexus of Viral- and Allo-ImmunityR01AI097423 · NIAID · EMORY UNIVERSITY · PI KIRK, ALLAN D. · 2012 to 2016
$2.6M
Adjuvant Therapies Improving the Anti-Rejection Effects of Costimulation BlockadeU01AI079223 · NIAID · EMORY UNIVERSITY · PI KIRK, ALLAN D. · 2009 to 2012
$2.4M
NIAID NIH HHS R01 AI097423NIAID NIH HHS U01 AI079223NIAID NIH HHS U19 AI051731NIAID NIH HHS U24 AI126683NIH HHS R24 OD010976
6 · The paper itself

Abstract

Costimulation blockade (CoB) via belatacept is a lower-morbidity alternative to calcineurin inhibitor (CNI)-based immunosuppression. However, it has higher rates of early acute rejection. These early rejections are mediated in part by memory T cells, which have reduced dependence on the pathway targeted by belatacept and increased adhesion molecule expression. One such molecule is leukocyte function antigen (LFA)-1. LFA-1 exists in two forms: a commonly expressed, low-affinity form and a transient, high-affinity form, expressed only during activation. We have shown that antibodies reactive with LFA-1 regardless of its configuration are effective in eliminating memory T cells but at the cost of impaired protective immunity. Here we test two novel agents, leukotoxin A and AL-579, each of which targets the high-affinity form of LFA-1, to determine whether this more precise targeting prevents belatacept-resistant rejection. Despite evidence of ex vivo and in vivo ligand-specific activity, neither agent when combined with belatacept proved superior to belatacept monotherapy. Leukotoxin A approached a ceiling of toxicity before efficacy, while AL-579 failed to significantly alter the peripheral immune response. These data, and prior studies, suggest that LFA-1 blockade may not be a suitable adjuvant agent for CoB-resistant rejection.

Indexed as

AbataceptAnimalsDisease Models, AnimalGlomerular Filtration RateGraft RejectionGraft SurvivalImmunologic MemoryImmunosuppressive AgentsKidney Function TestsKidney TransplantationLymphocyte Function-Associated Antigen-1Macaca mulattaPostoperative ComplicationsT-LymphocytesAbataceptImmunosuppressive AgentsLymphocyte Function-Associated Antigen-1animal models: nonhuman primatecostimulationfusion proteins and monoclonal antibodies: belataceptimmunobiologyimmunosuppressantimmunosuppression/immune modulationlymphocyte biology: traffickingmacrophage/monocyte biology: activationtranslational research/science

Identifiers

PMID27888551
PMCPMC5409867
OpenAlexW2549204609

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.