Evidence map›Paper›PMID 36045224›Full record

ArticlePediatric research2023

Can T-cell and B-cell excision circles predict development of inhibitors in pediatric hemophilia A?

Sarina Levy-Mendelovich, Atar Lev, Einat Avishai, Ivan Budnik, Rima Dardik, Asaaf Arie Barg, Raz Somech, Gili Kenet

Abstract read
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In one paragraph

Article in Pediatric research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.2field-weighted citation impact, top 48% 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

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. Article
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

8 authors at 2 institutions in 2 countries.

Sarina Levy-MendelovichNational Hemophilia Center, Sheba Medical Center, Tel Hashomer, Israel. Sarina.Levy@sheba.health.gov.il.ORCID http://orcid.org/0000-0003-3971-0336
Atar LevPediatric Department A and the Immunology Service, Jeffrey Modell Foundation canter, Edmond and Lily Safra Children's Hospital, Sheba Medical Center affiliated with Sackler school of medicine, Tel Aviv University, Tel Hashomer, Israel.
Einat AvishaiNational Hemophilia Center, Sheba Medical Center, Tel Hashomer, Israel.
Ivan BudnikDepartment of Pathophysiology, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.
Rima DardikNational Hemophilia Center, Sheba Medical Center, Tel Hashomer, Israel.
Asaaf Arie BargNational Hemophilia Center, Sheba Medical Center, Tel Hashomer, Israel.
Raz Somech *Pediatric Department A and the Immunology Service, Jeffrey Modell Foundation canter, Edmond and Lily Safra Children's Hospital, Sheba Medical Center affiliated with Sackler school of medicine, Tel Aviv University, Tel Hashomer, Israel.
Gili Kenet *National Hemophilia Center, Sheba Medical Center, Tel Hashomer, Israel.
Tel Aviv University · ILSechenov University · RU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHemophilia A (HA) therapy requires intravenous replacement infusions of factor (F) VIII concentrate. Inhibitors are high-affinity immunoglobulin G that are directed against FVIII and thereby render replacement therapy ineffective. This complication has significant prognostic implications. We aimed to examine the immune system involvement in inhibitor formation specifically T-cell excision circles (TRECs) and B-cell excision circles (KRECs), markers of new T and B cells, respectively, and examine them as surrogate markers for inhibitor formation.

methodsBlood samples were collected from 35 children with severe HA. Children were divided into two groups: with FVIII inhibitors and without FVIII inhibitors. TRECs and KRECs were measured in peripheral blood.

resultsA total of 11 patients with inhibitors and 24 without were evaluated. Children with inhibitors had higher levels of TRECs however not statistically significant (p = 0.085). CjKREC levels were higher in the inhibitor patients (p = 0.003). Moreover, the sj/cjKREC ratio was lower in the inhibitor patients (p = 0.015).

conclusionsOur findings may add to the notion that inhibitor formation is attributed to humoral immunity due to peripheral B-cell expansion and loss of peripheral tolerance. Improved knowledge regarding the involvement of the immune system in the formation of FVIII inhibitors will enable better therapy tailoring in the era of non-replacement therapies. IMPACT: The etiology of FVIII inhibitor formation is multifactorial, in which the immune system plays a pivotal role. Our findings may add to the notion that inhibitor formation is attributed to humoral immunity due to peripheral B-cell expansion and production of antibodies against FVIII. Improved knowledge regarding the involvement of the immune system in the development of FVIII inhibitors will enable the identification of patients prone to inhibitor development and better therapy tailoring in the new era of non-replacement therapies.

Indexed as

B-LymphocytesFactor VIIIHemophilia AT-LymphocytesChildCoagulantsHumansImmune SystemCoagulantsFactor VIII

Identifiers

PMID36045224
OpenAlexW4293770799

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.