EFFECT OF COMORBIDITY AND STANDARD THERAPY ON INTERFERON STATUS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
Notice bibliographique
Résumé
PV035 / #122 Poster Topic: AS04 - Biomarkers Background/Purpose Type I interferon (IFN-I) play a central role in the pathogenesis of Systemic lupus erythematosus (SLE). Overexpression of IFN-I occurs in 60-80% patients with SLE. Type I IFN-inducible gene expression, measured using the IFN gene signature (IFGNS), provides a method to assess IFN-I pathway activation in individual patients. Against a background of genetic predisposition, a trigger stimulus, possibly microbial, induces the production of IFN-I and autoantibodies leading to inflammation. Can only the clinical and immunological manifestations of SLE affect on IFNGS? The aim of our study was to describe any conditions, comorbidities and standard therapy of SLE depending on IFN gene signature. Methods This observational retrospective-prospective study included 76 patients (86% women, median aged 33 [25;43] years (median [interquartile range 25;75%]), with a definite diagnosis of SLE (SLICC 2012) attending a routine visit at our Clinic between February 2021 and June 2024. Baseline demographics, family history of immune-inflammatory rheumatic diseases among the first-line relatives, triggers, body mass index, smoking status, cardiovascular disease/stroke risk factors, renal disease, cancer, standard therapy (glucocorticoids, antimalarial, immunosuppressants) and IFNGS status (high/low) were analyzed in SLE patients. IFN status was assessed by the expression of IFN-inducible genes (MX1, RSAD2, EPSTI1) using real-time polymerase chain reaction. IFNGS was calculated as the average expression value of 3 selected genes. In patients, IFNGS was considered high when the average value of gene expression exceeded the average value of gene expression in donors. The control group consisted of 20 healthy donors comparable in sex and age with the SLE patients. Results The median disease duration was 2.3 [0.2;11.0] years, SLEDAI-2K 7 [4;11] score, SDI 0 [0;2] score. At the time of inclusion in the study, SLE patients had the following manifestations: hematological disorders - 49%, most commonly leucopenia – 45%, inflammatory arthritis - 39%, nephritis - 33% (most commonly class IV), cutaneous lupus - 28%, serositis -18%, mucosal ulcers - 8%, nervous system involvement - 7%. Among ‘non-criteria’ symptoms the most common were: livedo – 20%, Raynaud’s phenomenon - 12%, interstitial lung disease - 12%, lymphadenopathy - 8%, unexplained fever - 7%. Concomitant APS and Sjögren’s syndrome were found in 12% and 38% of patients, respectively. The majority of patients at the time of inclusion were taking glucocorticoids (83%) at low doses (10.0 [7.5; 20.0] mg/day prednisolone) in combination with hydroxychloroquine (80%) at a dose of 200 mg/day. Immunosuppressants were used less frequently (in 36% of patients), mainly - mycophenolate mofetil (18%), cyclophosphamide, methotrexate and azathioprine in single cases. In addition, 13/76 (17%) patients were not receiving any therapy. Anti-B cell biologic (mainly rituximab) according to the inclusion criteria were used more than 2 years ago in 8% of patients. IFNGS-high was detected in 72% of SLE patients. IFNGS-high patients were younger at the time of inclusion (31 [25; 41] and 40 [32; 49] years, p<0.05). We identified less hypertension (24% and 52%) and dyslipidemia (13% and 38%) in IFGNS-high patients vs IFNGS-low patients with SLE. No effect of standard therapy for SLE on IFN-inducible genes expression was found. Conclusions In SLE patients, IFN-I is independent of family history of autoimmune disease, any provoking factors, gender, weight, smoking, and any comorbidity. The lower incidence of hypertension and dyslipidemia in IFNGS-high patients is due to the younger age of them. Standard therapy has no significant effect on the expression of certain IFN-inducible genes.
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 | 0,000 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 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 ».