Evidence map›Paper›PMID 39391687›Full record

ArticleFrontiers in allergy2024

A novel assay of excess plasma kallikrein-kinin system activation in hereditary angioedema.

Dan Sexton, Ryan Faucette, Melody Rivera-Hernandez, Jon A Kenniston, Nikolaos Papaioannou, Janja Cosic, Kris Kopacz, Gary Salmon, Chantal Beauchemin, Salomé Juethner and 1 more

Erratum issuedAbstract read
In one paragraph

Article in Frontiers in allergy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Review
  2. The journal of allergy and clinical immunology. Global · 2026
    Article
  3. Article
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Dan SextonTakeda Development Center Americas Inc., Cambridge, MA, United States.
Ryan FaucetteTakeda Development Center Americas Inc., Cambridge, MA, United States.
Melody Rivera-HernandezTakeda Development Center Americas Inc., Cambridge, MA, United States.
Jon A KennistonTakeda Development Center Americas Inc., Cambridge, MA, United States.
Nikolaos PapaioannouTakeda Development Center Americas Inc., Cambridge, MA, United States.
Janja CosicTakeda Development Center Americas Inc., Cambridge, MA, United States.
Kris KopaczTakeda Development Center Americas Inc., Cambridge, MA, United States.
Gary SalmonCharles River Laboratories, Harlow, United Kingdom.
Chantal BeaucheminTakeda Development Center Americas Inc., Cambridge, MA, United States.
Salomé JuethnerTakeda Pharmaceuticals USA, Inc., Lexington, MA, United States.
Dave YeungTakeda Development Center Americas Inc., Cambridge, MA, United States.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Cleaved high-molecular-weight kininogen (HKa) is a disease state biomarker of kallikrein-kinin system (KKS) activation in patients with hereditary angioedema due to C1 inhibitor deficiency (HAE-C1INH), the endogenous inhibitor of plasma kallikrein (PKa). Objective: Develop an HKa-specific enzyme-linked immunosorbent assay (ELISA) to monitor KKS activation in the plasma of HAE-C1INH patients. Methods: A novel HKa-specific antibody was discovered by antibody phage display and used as a capture reagent to develop an HKa-specific ELISA. Results: Specific HKa detection following KKS activation was observed in plasma from healthy controls but not in prekallikrein-, high-molecular-weight kininogen-, or coagulation factor XII (FXII)-deficient plasma. HKa levels in plasma collected from HAE-C1INH patients in a disease quiescent state were higher than in plasma from healthy controls and increased further in HAE-C1INH plasma collected during an angioedema attack. The specificity of the assay for PKa-mediated HKa generation in minimally diluted plasma activated with exogenous FXIIa was demonstrated using a specific monoclonal antibody inhibitor (lanadelumab, IC Conclusions: An ELISA was developed for the specific and quantitative detection of HKa in human plasma to support HAE-C1INH drug development. Improved quantification of the HKa biomarker may facilitate further pathophysiologic insight into HAE-C1INH and other diseases mediated by a dysregulated KKS and may enable the design of highly potent inhibitors targeting this pathway.

Indexed as

biomarkersbradykininhereditary angioedemaphage displayplasma kallikrein

Identifiers

PMID39391687
PMCPMC11464748

What OpenQuestion holds

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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.