Evidence map›Paper›PMID 29459849›Full record

ArticleFrontiers in endocrinology2018

Widely Used Commercial ELISA Does Not Detect Precursor of Haptoglobin2, but Recognizes Properdin as a Potential Second Member of the Zonulin Family.

Lucas Scheffler, Alyce Crane, Henrike Heyne, Anke Tönjes, Dorit Schleinitz, Christian H Ihling, Michael Stumvoll, Rachel Freire, Maria Fiorentino, Alessio Fasano and 2 more

Open access · goldAbstract read
In one paragraph

Article in Frontiers in endocrinology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
97citing papers in PubMed, 2 pooled it
11.8field-weighted citation impact, top 1% 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

97 citing papers in PubMed, 2 syntheses or guidelines pooled it, 140 citations in OpenAlex.

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  10. Gut microbes · 2026
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  19. Intermittent Fasting andNutrients · 2026
    Article
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37 more citing papers are in PubMed but not listed here.

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

12 authors at 5 institutions in 2 countries.

Lucas SchefflerLeipzig University Medical Center, IFB Adiposity Diseases, Leipzig, Germany.
Alyce CraneLeipzig University Medical Center, IFB Adiposity Diseases, Leipzig, Germany.
Henrike HeyneLeipzig University Medical Center, IFB Adiposity Diseases, Leipzig, Germany.
Anke TönjesDivisions of Endocrinology and Nephrology, University of Leipzig, Leipzig, Germany.
Dorit SchleinitzLeipzig University Medical Center, IFB Adiposity Diseases, Leipzig, Germany.
Christian H IhlingDepartment of Pharmaceutical Chemistry and Bioanalytics, Institute of Pharmacy, Martin-Luther-University Halle-Wittenberg, Halle, Germany.
Michael StumvollDivisions of Endocrinology and Nephrology, University of Leipzig, Leipzig, Germany.
Rachel FreireMucosal Immunology And Biology Research Center, Massachusetts General Hospital--Harvard Medical School, Boston, MA, United States.
Maria FiorentinoMucosal Immunology And Biology Research Center, Massachusetts General Hospital--Harvard Medical School, Boston, MA, United States.
Alessio FasanoMucosal Immunology And Biology Research Center, Massachusetts General Hospital--Harvard Medical School, Boston, MA, United States.
Peter KovacsLeipzig University Medical Center, IFB Adiposity Diseases, Leipzig, Germany.
John T HeikerFaculty of Biosciences, Pharmacy and Psychology, Institute of Biochemistry, University of Leipzig, Leipzig, Germany.
Leipzig University · DEIFB Adiposity Diseases · DEMassachusetts General Hospital · USHarvard University · USMartin Luther University Halle-Wittenberg · DE

Funding

Microbiome-derived Metabolites Linked to Celiac Disease Onset in Infants at RiskR01DK104344 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI FASANO, ALESSIO · 2016 to 2020
$3.4M
NIDDK NIH HHS R01 DK104344
6 · The paper itself

Abstract

backgroundThere is increasing evidence for the role of impaired intestinal permeability in obesity and associated metabolic diseases. Zonulin is an established serum marker for intestinal permeability and identical to pre-haptoglobin2. Here, we aimed to investigate the relationship between circulating zonulin and metabolic traits related to obesity.

methodsSerum zonulin was measured by using a widely used commercial ELISA kit in 376 subjects from the metabolically well-characterized cohort of Sorbs from Germany. In addition, haptoglobin genotype was determined in DNA samples from all study subjects.

resultsAs zonulin concentrations did not correlate to the haptoglobin genotypes, we investigated the specificity of the zonulin ELISA assay using antibody capture experiments, mass spectrometry, and Western blot analysis. Using serum samples that gave the highest or lowest ELISA signals, we detected several proteins that are likely to be captured by the antibody in the present kit. However, none of these proteins corresponds to pre-haptoglobin2. We used increasing concentrations of recombinant pre-haptoglobin2 and complement C3 as one of the representative captured proteins and the ELISA kit did not detect either. Western blot analysis using both the polyclonal antibodies used in this kit and monoclonal antibodies rose against zonulin showed a similar protein recognition pattern but with different intensity of detection. The protein(s) measured using the ELISA kit was (were) significantly increased in patients with diabetes and obesity and correlated strongly with markers of the lipid and glucose metabolism. Combining mass spectrometry and Western blot analysis using the polyclonal antibodies used in the ELISA kit, we identified properdin as another member of the zonulin family.

conclusionOur study suggests that the zonulin ELISA does not recognize pre-haptoglobin2, rather structural (and possibly functional) analog proteins belonging to the mannose-associated serine protease family, with properdin being the most likely possible candidate.

Indexed as

diabetesELISAintestinal permeabilitylipid metabolismmetabolic diseasesobesityprecursor of haptoglobin2properdin

Identifiers

PMID29459849
PMCPMC5807381
OpenAlexW2791045211

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.