Evidence map›Paper›PMID 33640906›Full record

ArticleBlood cancer journal2021

Polymorphisms in CXCR3 ligands predict early CXCL9 recovery and severe chronic GVHD.

Hao Dai, Sivaramakrishna P Rachakonda, Olaf Penack, Igor W Blau, Olga Blau, Aleksandar Radujkovic, Carsten Müller-Tidow, Peter Dreger, Rajiv Kumar, Thomas Luft

Open access · goldAbstract read
In one paragraph

Article in Blood cancer journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed, 11 citations in OpenAlex.

  1. Trial
  2. Review
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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

10 authors at 3 institutions in 1 country.

Hao DaiDepartment of Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
Sivaramakrishna P RachakondaDepartment of Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
Olaf PenackDivision of Hematology, Oncology and Tumorimmunology, Charité University Medicine Berlin, Berlin, Germany.
Igor W BlauDivision of Hematology, Oncology and Tumorimmunology, Charité University Medicine Berlin, Berlin, Germany.
Olga BlauDivision of Hematology, Oncology and Tumorimmunology, Charité University Medicine Berlin, Berlin, Germany.
Aleksandar RadujkovicDepartment of Medicine V, University Hospital Heidelberg, Heidelberg, Germany.
Carsten Müller-TidowDepartment of Medicine V, University Hospital Heidelberg, Heidelberg, Germany.
Peter DregerDepartment of Medicine V, University Hospital Heidelberg, Heidelberg, Germany.ORCID 0000-0002-7429-8570
Rajiv KumarDepartment of Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
Thomas LuftDepartment of Medicine V, University Hospital Heidelberg, Heidelberg, Germany. Thomas.luft@med.uni-heidelberg.de.ORCID 0000-0002-0387-1640
Heidelberg University · DECharité - Universitätsmedizin Berlin · DEGerman Cancer Research Center · DE

Funding

Deutsche Forschungsgemeinschaft (German Research Foundation) TL820.8-1EC | EC Seventh Framework Programm | FP7 Health (FP7-HEALTH - Specific Programme "Cooperation": Health) 306240
6 · The paper itself

Abstract

Chronic graft-versus-host disease (cGVHD) is a major cause of mortality and morbidity after allogeneic stem cell transplantation (alloSCT). The individual risk of severe cGVHD remains difficult to predict and may involve CXCR3 ligands. This study investigated the role of single-nucleotide polymorphisms (SNPs) of CXCL4, CXCL9, CXCL10, and CXCL11, and their day +28 serum levels, in cGVHD pathogenesis. Eighteen CXCR3 and CXCL4, CXCL9-11 SNPs as well as peri-transplant CXCL9-11 serum levels were analyzed in 688 patients without (training cohort; n = 287) or with statin-based endothelial protection cohort (n = 401). Clinical outcomes were correlated to serum levels and SNP status. Significant polymorphisms were further analyzed by luciferase reporter assays. Findings were validated in an independent cohort (n = 202). A combined genetic risk comprising four CXCR3 ligand SNPs was significantly associated with increased risk of severe cGVHD in both training cohort (hazard ratio (HR) 2.48, 95% confidence interval (CI) 1.33-4.64, P = 0.004) and validation cohort (HR 2.95, 95% CI 1.56-5.58, P = 0.001). In reporter assays, significantly reduced suppressive effects of calcineurin inhibitors in constructs with variant alleles of rs884304 (P < 0.001) and rs884004 (P < 0.001) were observed. CXCL9 serum levels at day +28 after alloSCT correlated with both genetic risk and risk of severe cGVHD (HR 1.38, 95% CI 1.10-1.73, P = 0.006). This study identifies patients with high genetic risk to develop severe cGVHD.

Indexed as

Polymorphism, Single NucleotideAdolescentAdultAgedChemokine CXCL9Chronic DiseaseCohort StudiesFemaleGraft vs Host DiseaseHumansMaleMiddle AgedReceptors, CXCR3Young AdultChemokine CXCL9CXCL9 protein, humanCXCR3 protein, humanReceptors, CXCR3

Identifiers

PMID33640906
PMCPMC7914250
OpenAlexW3134214090

What Socratic holds

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LicenceCC BY
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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 Socratic graph.