Autoantibodies Against Lysosome Associated Membrane Protein-2 (LAMP-2) in Pediatric Chronic Primary Systemic Vasculitis
Notice bibliographique
Résumé
Background: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a small vessel vasculitis in adults and children that commonly affects the kidneys. Although the frequent antigenic, and presumed pathogenic, targets of ANCA in AAV are proteinase-3 (PR3) and myeloperoxidase (MPO), ANCA against lysosome associated membrane protein-2 (LAMP-2), a lesser known ANCA antigen that is expressed on the glomerular endothelium, are present in some adults with AAV-associated renal disease. LAMP-2-ANCA has not been assessed in children with chronic systemic vasculitis, and, if present, would be a potentially valuable biomarker given that treatment decisions for these pediatric patients at diagnosis are largely informed by kidney function. Methods: A custom ELISA, using commercially available reagents, was designed to detect autoantibodies to human LAMP-2 in serum. Sera obtained from 51 pediatric patients at the time of diagnosis of chronic primary systemic vasculitis (predominantly AAV) were screened. LAMP-2-ANCA titers were evaluated for correlation with clinical metrics of disease activity (pediatric vasculitis activity score [pVAS], C-reactive protein [CRP] concentration, and erythrocyte sedimentation rate [ESR]), MPO- and PR3-ANCA titers, and renal function (glomerular filtration rate [GFR], renal-specific pVAS, and serum creatinine concentration). Results: LAMP-2-ANCA (>1,000 ng/ml) were detected in 35% (n = 18) of pediatric systemic vasculitis patients, of which, 10 (20% of all patients) were found to have high positive titers (>1,500 ng/ml). Undetectable or negative titres (<500 ng/ml) were identified in 12% (n = 6) of patients, those with titers between 500 and 1,000 ng/ml were considered low with unknown clinical relevance (53%, n = 27). Although LAMP-2-ANCA titers did not significantly differ between patients with AAV versus ANCA-negative vasculitis, only AAV patients had high concentrations (>1,500 ng/ml) of LAMP-2-ANCA. LAMP-2-ANCA titers did not correlate with measures of disease activity (pVAS, CRP, or ESR) at the time of diagnosis. In contrast, for patients with 12-month post diagnosis follow-up, a negative correlation was observed between the change in GFR (from diagnosis to 12-month follow-up) and LAMP-2-ANCA titer at diagnosis. Conclusions: Moderate to high LAMP-2-ANCA titers were detected in 35% (18/51) of children with chronic systemic vasculitis affecting small-to-medium vessels. Although the highest concentrations of LAMP-2-ANCA in this population were observed in individuals positive for classic ANCA (MPO- or PR3-ANCA), similar to previous reports on adult patients, LAMP-2-ANCA titers do not correlate with classic ANCA titers or with overall disease activity at diagnosis. Renal disease is a common manifestation in systemic small-medium vessel vasculitis (both in adults and children, though more severe in children) and our preliminary data suggest LAMP-2-ANCA at diagnosis may be a risk factor for more severe renal disease.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».