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Record W4289784922 · doi:10.1164/rccm.202201-0011oc

Pulmonary Surfactant Proteins Are Inhibited by Immunoglobulin A Autoantibodies in Severe COVID-19

2022· article· en· W4289784922 on OpenAlexafffund
Tobias Sinnberg, Christa Lichtensteiger, Omar Hasan Ali, Oltin T. Pop, Ann-Kristin Jochum, Lorenz Risch, Silvio D. Brugger, Ana Velić, David Bomze, Philipp Köhler, Pietro Vernazza, Werner C. Albrich, Christian R. Kahlert, Marie-Therese Abdou, Nina Wyss, Kathrin Hofmeister, Heike Niessner, Carl Zinner, Mara Gilardi, Alexandar Tzankov, Martin Röcken, Alex Dulovic, Srikanth Mairpady Shambat, Natalia Ruétalo, Philipp K. Buehler, Thomas Scheier, Wolfram Jochum, Lukas Kern, Samuel Henz, Tino Schneider, Gabriela M. Kuster, Maurin Lampart, Martin Siegemund, Roland Bingisser, Michael Schindler, Nicole Schneiderhan‐Marra, Hubert Kalbacher, Kathy D. McCoy, Werner Spengler, Martin Brutsche, Boris Maček, Raphael Twerenbold, Josef Penninger, Matthias S. Matter, Lukas Flatz

Bibliographic record

VenueAmerican Journal of Respiratory and Critical Care Medicine · 2022
Typearticle
Languageen
FieldMedicine
TopicNeonatal Respiratory Health Research
Canadian institutionsUniversity of CalgaryUniversity of British Columbia
FundersCanadian Institutes of Health ResearchÖsterreichischen Akademie der WissenschaftenSchweizerische HerzstiftungDeutsche ForschungsgemeinschaftFondation BotnarAustrian Science FundInnovative Medicines CanadaSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungNational Science Foundation
KeywordsAutoantibodyPulmonary surfactantMedicineImmunologyLungPneumoniaAntibodyImmune systemDLCOInternal medicineBiologyDiffusing capacityLung function

Abstract

fetched live from OpenAlex

Abstract Rationale Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome with fatal outcomes. Evidence suggests that dysregulated immune responses, including autoimmunity, are key pathogenic factors. Objectives To assess whether IgA autoantibodies target lung-specific proteins and contribute to disease severity. Methods We collected 147 blood, 9 lung tissue, and 36 BAL fluid samples from three tertiary hospitals in Switzerland and one in Germany. Severe COVID-19 was defined by the need to administer oxygen. We investigated the presence of IgA autoantibodies and their effects on pulmonary surfactant in COVID-19 using the following methods: immunofluorescence on tissue samples, immunoprecipitations followed by mass spectrometry on BAL fluid samples, enzyme-linked immunosorbent assays on blood samples, and surface tension measurements with medical surfactant. Measurements and Main Results IgA autoantibodies targeting pulmonary surfactant proteins B and C were elevated in patients with severe COVID-19 but not in patients with influenza or bacterial pneumonia. Notably, pulmonary surfactant failed to reduce surface tension after incubation with either plasma or purified IgA from patients with severe COVID-19. Conclusions Our data suggest that patients with severe COVID-19 harbor IgA autoantibodies against pulmonary surfactant proteins B and C and that these autoantibodies block the function of lung surfactant, potentially contributing to alveolar collapse and poor oxygenation.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.037
GPT teacher head0.381
Teacher spread0.343 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations33
Published2022
Admission routes2
Has abstractyes

Explore more

Same venueAmerican Journal of Respiratory and Critical Care MedicineSame topicNeonatal Respiratory Health ResearchFrench-language works237,207