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Record W4361297552 · doi:10.14785/lymphosign-2023-0003

Lung histopathology evaluation of an X-MAID patient with a novel mutation in <i>MSN</i>

2023· article· en· W4361297552 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
venuePublished in a venue whose home country is Canada.

Bibliographic record

VenueLymphoSign Journal · 2023
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmunodeficiency and Autoimmune Disorders
Canadian institutionsHospital for Sick ChildrenUniversity of Toronto
Fundersnot available
KeywordsMoesinRadixinEzrinPathologyLungMedicineBiologyImmunologyInternal medicineCytoskeletonCellGenetics

Abstract

fetched live from OpenAlex

Background: The cell cytoskeleton is regulated by the ezrin-radixin-moesin (ERM) family of proteins, forming links between transmembrane proteins and the underlying actin cytoskeleton. Phosphorylation and activation of these proteins enable interactions with partners critically involved in shape regulation, such as actin filaments, transmembrane proteins, and scaffolding proteins. The MSN gene encodes moesin, which is ubiquitously expressed in lungs, spleen, kidney, endothelial cells of vessels, lymphocytes, and neutrophils. Deficiency or dysregulation of moesin, called X-linked moesin-associated immunodeficiency (X-MAID), is characterized by severe leukopenia affecting T cells, B cells, and neutrophils. To date, the clinical picture of patients with X-MAID is variable. Aim: We describe the presentation, immune-workup, and lung histopathology findings of a young male patient with X-MAID and multi-organ involvement, whose severe pulmonary vein stenosis necessitated a double lung transplant. Methods: A thorough review of the patient’s chart was performed. Results: The patient presented with a history of recurrent respiratory tract infections, oral thrush, and 3 major bacterial infections requiring admission and antibiotic therapy. His immune evaluation was remarkable for low T cells, and normal numbers of B and NK cells. At age 4 years he underwent a double lung transplant due to severe pulmonary vein stenosis and pulmonary hypertension. He further developed chronic kidney injury post-transplant. Clinical trio whole exome sequencing revealed a novel hemizygous variant in the MSN gene (c.278dupT; p.L93FfsX21), predicted to cause loss-of-function in moesin. Histologic evaluation of the lung tissue before transplantation identified profound abnormalities in alveoli formation. Conclusion: Patients with moesin deficiency may present during infancy or childhood with a severe form of the disease, including combined immunodeficiency with lymphopenia and neutropenia, while adults may have a milder clinical picture. The novel MSN mutation described here adds to the known spectrum of disease and highlights the non-redundant functions of moesin, particularly in the lung. Statement of Novelty: We report the first lung histopathological description of an X-MAID case, in a pediatric patient with recurrent infections, cytopenia, and autoimmunity who underwent a double lung transplant.

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.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation 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 score0.555
Threshold uncertainty score0.425

Codex and Gemma teacher scores by category

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

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 head0.014
GPT teacher head0.251
Teacher spread0.237 · 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