Evidence map›Paper›PMID 33217039›Full record

ArticleBritish journal of clinical pharmacology2021

Two tagging single-nucleotide polymorphisms to capture HLA-DRB1*07:01-DQA1*02:01-DQB1*02:02 haplotype associated with asparaginase hypersensitivity.

Nóra Kutszegi, András Gézsi, Ágnes F Semsei, Judit Müller, Réka Simon, Erika Rozália Kovács, Katalin Hegedüs, Gábor T Kovács, Csaba Szalai, Dániel J Erdélyi

Open access · hybridAbstract read
In one paragraph

Article in British journal of clinical pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
0.9field-weighted citation impact, top 22% 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

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.

  1. Pooled it
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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.

Nóra Kutszegi2nd Department of Paediatrics, Semmelweis University, Budapest, Hungary.ORCID 0000-0001-5957-3215
András GézsiMTA-SE Immune-Proteogenomics Extracellular Vesicle Research Group, Budapest, Hungary.
Ágnes F SemseiDepartment of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
Judit Müller2nd Department of Paediatrics, Semmelweis University, Budapest, Hungary.
Réka SimonChild Health's Centre, Borsod-Abauj-Zemplen County Hospital, Miskolc, Hungary.
Erika Rozália Kovács2nd Department of Paediatrics, Semmelweis University, Budapest, Hungary.
Katalin Hegedüs2nd Department of Paediatrics, Semmelweis University, Budapest, Hungary.
Gábor T Kovács2nd Department of Paediatrics, Semmelweis University, Budapest, Hungary.
Csaba SzalaiDepartment of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
Dániel J Erdélyi2nd Department of Paediatrics, Semmelweis University, Budapest, Hungary.
Semmelweis University · HUBorsod-Abaúj-Zemplén Megyei Kórház és Egyetemi Oktató Kórház · HUBudapest University of Technology and Economics · HU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsAsparaginase (ASP) hypersensitivity is a well-known challenge in the treatment of lymphoblastic malignancies. In terms of cost considerations, the cheap native Escherichia coli ASP, the most immunogenic form of this medication, is used in the first line in middle-income countries. Previously, the role of the HLA-DRB1*07:01-DQA1*02:01-DQB1*02:02 haplotype had been established to associate with E. coli ASP hypersensitivity. We investigated a possible cost-effective genetic testing method to identify patients harbouring the risk HLA haplotype in order to pave the way for safer ASP treatment.

methodsIn 241 patients with previously determined HLA-DRB1*07:01-DQA1*02:01-DQB1*02:02 haplotype and known ASP hypersensitivity status, 4 candidate HLA-tagging single-nucleotide polymorphisms (SNP)s were measured, and the performance of the different sets of these tag SNPs was evaluated.

resultsWe identified a combination of 2 SNPs - rs28383172 and rs7775228 - as a tag for HLA-DRB1*07:01-DQA1*02:01-DQB1*02:02 haplotype with sensitivity and specificity values >95%. In line with previous findings, we found complete concordance between HLA-DRB1*07:01 and rs28383172. With bioinformatics methods, the results were also confirmed in the 1000 Genomes dataset in different ethnic groups.

conclusionRs28383172 and rs7775228 are suitable for identifying HLA-DRB1*07:01-DQA1*02:01-DQB1*02:02 carriers. Compared to the rest of the population, patients with hypersensitivity-prone genotype would benefit more from the administration of less immunogenic PEGylated ASP before the hypersensitivity evolves, incurring minimal extra cost.

Indexed as

AsparaginaseDrug HypersensitivityHLA-DRB1 ChainsAllelesEscherichia coliGene FrequencyGenetic Predisposition to DiseaseHaplotypesHLA-DQ alpha-ChainsHLA-DQ beta-ChainsHumansPolymorphism, Single NucleotideAsparaginaseHLA-DQ alpha-ChainsHLA-DQ beta-ChainsHLA-DRB1 Chainsacute lymphoblastic leukaemiaallergyasparaginase hypersensitivityHLA-DRB1*07:01screening testtagging SNPs

Identifiers

PMID33217039
PMCPMC8247313
OpenAlexW3099082940

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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.