A novel missense variant in CTLA4 associated with immune dysregulation
Why this work is in the frame
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Bibliographic record
Abstract
Background: Cytotoxic T lymphocyte-associated antigen-4 (CTLA4) haploinsufficiency is a primary immunoregulatory disorder characterized by a broad clinical spectrum including combined immunodeficiency, autoimmunity, enteropathy, lymphoproliferation, and malignancy. Aim: We aim to broaden the recognized phenotypic and genetic spectrum of patients with variants in CTLA4. Methods: We report the case of a patient with persistent bicytopenia and an episode of soft tissue infection and associated bacteremia. Targeted genetic sequencing was performed using next-generation sequencing on the Illumina platform with Sanger sequencing for low-coverage regions through Cincinnati Children’s Hospital in addition to immune evaluation. Results: The proband presented at 14 years of age with cellulitis, and was found to have Bacillus cereus bacteremia, along with neutropenia and thrombocytopenia that persisted following infection resolution. Immune evaluation revealed T cell lymphopenia with preserved humoral immunity, and subsequently NK cell lymphopenia. A targeted ALPS genetic panel identified a novel heterozygous variant in the CTLA4 NM_005214.5(CTLA4):c.160G>T (p.Ala54Ser). Conclusion: A novel heterozygous CTLA4 variant caused immune dysregulation and immunodeficiency, in keeping with the described features of CTLA4 haploinsufficiency. Statement of novelty: We describe a previously unreported missense variant in CTLA4 leading to immune dysregulation and cytopenias, successfully managed with targeted abatacept therapy.
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Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it