Evidence map›Paper›PMID 33479441›Full record

ArticleScientific reports2021

Serum naturally occurring anti-TDP-43 auto-antibodies are increased in amyotrophic lateral sclerosis.

Elisa Conti, Gessica Sala, Susanna Diamanti, Marco Casati, Christian Lunetta, Francesca Gerardi, Claudia Tarlarini, Lorena Mosca, Nilo Riva, Yuri Falzone and 4 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 2 pooled it
1.6field-weighted citation impact, top 14% 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

12 citing papers in PubMed, 2 syntheses or guidelines pooled it, 17 citations in OpenAlex.

  1. Pooled it
  2. Chitinases as a potential diagnostic and prognostic biomarker for amyotrophic lateral sclerosis: a systematic review and meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024
    Pooled it
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  6. The presence and clinical significance of autoantibodies in amyotrophic lateral sclerosis: a narrative review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024
    Review
  7. Review
  8. Article
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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

14 authors at 6 institutions in 1 country.

Elisa ContiLab of Neurobiology, School of Medicine and Surgery and Milan Center for Neuroscience, University of Milano-Bicocca, Monza, Italy.
Gessica SalaLab of Neurobiology, School of Medicine and Surgery and Milan Center for Neuroscience, University of Milano-Bicocca, Monza, Italy.
Susanna DiamantiLab of Neurobiology, School of Medicine and Surgery and Milan Center for Neuroscience, University of Milano-Bicocca, Monza, Italy.
Marco CasatiLaboratory of Chemical and Clinical Analyses, "San Gerardo" Hospital, ASST Monza, Monza, Italy.
Christian LunettaNEuroMuscular Omnicentre (NEMO), Fondazione Serena Onlus, Milano, Italy.
Francesca GerardiNEuroMuscular Omnicentre (NEMO), Fondazione Serena Onlus, Milano, Italy.
Claudia TarlariniNEuroMuscular Omnicentre (NEMO), Fondazione Serena Onlus, Milano, Italy.
Lorena MoscaMedical Genetics Unit, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy.
Nilo RivaExperimental Neuropathology Unit, Division of Neuroscience, IRCCS "San Raffaele" Scientific Institute, Milano, Italy.
Yuri FalzoneExperimental Neuropathology Unit, Division of Neuroscience, IRCCS "San Raffaele" Scientific Institute, Milano, Italy.
Massimo FilippiNeurology Unit, Neurorehabilitation Unit, Neurophysiology Service, Division of Neuroscience, IRCCS "San Raffaele" Scientific Institute, Milano, Italy.
Ildebrando AppollonioLab of Neurobiology, School of Medicine and Surgery and Milan Center for Neuroscience, University of Milano-Bicocca, Monza, Italy.
Carlo FerrareseLab of Neurobiology, School of Medicine and Surgery and Milan Center for Neuroscience, University of Milano-Bicocca, Monza, Italy.
Lucio TremolizzoLab of Neurobiology, School of Medicine and Surgery and Milan Center for Neuroscience, University of Milano-Bicocca, Monza, Italy. lucio.tremolizzo@unimib.it.
University of Milano-Bicocca · ITAzienda Ospedaliera San Gerardo · ITCentro Clinico Nemo · ITIstituti di Ricovero e Cura a Carattere Scientifico · ITAzienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda · ITVita-Salute San Raffaele University · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Amyotrophic Lateral Sclerosis (ALS) patients express significant clinical heterogeneity that often hinders a correct diagnostic definition. Intracellular deposition of TDP-43, a protein involved in RNA metabolism characterizes the pathology. Interestingly, this protein can be detected in serum, wherein cognate naturally-occurring auto-antibodies (anti-TDP-43 NAb) might be also present, albeit they have never been documented before. In this exploratory study, we quantified the levels of both anti-TDP-43 NAb and TDP-43 protein as putative accessible markers for improving the ALS diagnostic process by using ELISA in N = 70 ALS patients (N = 4 carrying TARDBP mutations), N = 40 age-comparable healthy controls (CTRL), N = 20 motor neuron disease mimics (MN-m), N = 20 Alzheimer's disease (AD) and N = 15 frontotemporal lobar degeneration (FTLD) patients. Anti-TDP-43 NAb were found to be significantly increased in ALS patients compared to all the other groups (p < 0.001). On the other hand, the distribution of serum levels of TDP-43 protein was highly variable among the various groups. Levels were increased in ALS patients, albeit the highest values were detected in MN-m patients. NAb and protein serum levels failed to correlate. For the first time, we report that serum anti-TDP-43 NAb are detectable in human serum of both healthy controls and patients affected by a variety of neurodegenerative disorders; furthermore, their levels are increased in ALS patients, representing a potentially interesting trait core marker of this disease. Further studies are needed to clarify the exact role of the NAb. This information might be extremely useful for paving the way toward targeting TDP-43 by immunotherapy in ALS.

Indexed as

AdultAgedAged, 80 and overAlzheimer DiseaseAmyotrophic Lateral SclerosisAntibodies, Anti-IdiotypicAutoantibodiesDNA-Binding ProteinsFemaleFrontotemporal DementiaFrontotemporal Lobar DegenerationHumansInclusion BodiesMaleMiddle AgedMotor Neuron DiseaseAntibodies, Anti-IdiotypicAutoantibodiesDNA-Binding ProteinsTARDBP protein, human

Identifiers

PMID33479441
PMCPMC7820419
OpenAlexW3122580181

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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.