Type 1 reaction leprosy patients display distinct immune-regulatory capacity before onset of symptoms
Notice bibliographique
Résumé
Abstract Leprosy is a chronic disease of the skin and peripheral nerves caused by Mycobacterium leprae . A major public health and clinical problem are leprosy reactions, which are inflammatory episodes that often contribute to nerve damage and disability. Type I reversal reactions (T1R) can occur after microbiological cure of leprosy and affect up to 50% of leprosy patients. Early intervention to prevent T1R and, hence, nerve damage, is a major focus of current leprosy control efforts. In a prospective study, we enrolled and collected samples from 32 leprosy patients before the onset of T1R. Whole blood aliquots were challenged with M. leprae sonicate or media and total RNA was extracted. After a three-year follow-up, the transcriptomic response was compared between cells from 22 patients who remained T1R-free and 10 patients who developed T1R during that period. Our analysis focused on differential transcript (i.e. isoform) expression and usage. Results showed that, at baseline, cells from T1R-destined and T1R-free subjects had no main difference in their transcripts expression and usage. However, the cells of T1R patients displayed a transcriptomic immune response to M. leprae antigens that was significantly different from the one of cells from leprosy patients who remained T1R-free. Transcripts with significantly higher upregulation in the T1R-destined group, compared to the cells from T1R-free patients, were enriched for pathways and GO terms involved in response to intracellular pathogens, apoptosis regulation and inflammatory processes. Similarly, transcript usage analysis pinpointed different transcript proportions in response to the in-vitro challenge of cells from T1R-destined patients. Hence, transcript usage in concert with transcript expression suggested a dysregulated inflammatory response including increased apoptosis regulation in the peripheral blood cells of T1R-destined patients before the onset of T1R symptoms. Combined, these results provided detailed insight into the pathogenesis of T1R. Author Summary The prevention and clinical management of type 1 reactions (T1R) remain an important unmet need to reduce nerve damage in leprosy patients. It is not known why 30-50% of leprosy patients will develop T1R. This knowledge gap underlies the need for a better mechanistic understanding of T1R that could lead to biomarker candidates to identify leprosy patients who are at high risk of developing T1R. Here, we used a prospective design in which leprosy patients were enrolled before the onset of T1R.Whole blood samples were obtained at enrollment, aliquots were left unstimulated or were stimulated M. leprae antigens and total RNA was extracted. Patients were followed for three years at which time 10 out of 32 participants had developed T1R. Subsequent transcript expression and usage analyses revealed that groups differed little in their isoform landscape at baseline. Following stimulation, transcriptomic response differences became pronounced. Transcripts with higher response in T1R group preferentially involved genes of intracellular defense and inflammatory pathways. Among these transcripts, non-coding ones had higher frequency in T1R. Our study provided new insights into the T1R pathogenesis by suggesting a role for non-coding transcripts into the immune dysregulations of T1R and providing additional candidate genes and their isoforms to be further investigated.
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| 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 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 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 tête enseignante, 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 ».