Cytokine profiles of lupus patients with or without nephritis
Notice bibliographique
Résumé
It remains unclear why some patients with SLE develop lupus nephritis (LN) and others do not. A reasonable hypothesis is that the inflammatory/immunomodulatory mechanisms in patients with LN are either qualitatively different than in nonrenal (NR) lupus, or that similar pathways are activated but the magnitude of activation is greater in LN. Studies of individual or small groups of candidate cytokines support this idea. To test this hypothesis we examined baseline serum and peripheral blood mononuclear cell (PBMC) cytokine profiles of SLE patients with active LN or NR (mainly arthritis) lupus before entry into a clinical trial of Laquinimod (Teva Pharmaceuticals) as an adjunct anti-inflammatory agent for SLE. We sought to determine whether NR or LN was associated with a distinct pattern or level of cytokine expression. Serum and PBMC from 49 NR and 16 LN patients were collected. PBMC were cultured in medium with or without lipopolysaccharide (LPS), phytohemagglutinin (PHA), or tetanus toxoid (TT). PBMC proliferation was measured after 48 hours, and 38 cytokines were measured in the PBMC-conditioned supernatant by Luminex multiplexing. The same cytokines were measured in the sera. LN patients were younger (37 ± 9 vs. 47 ± 14, P < 0.006), had a higher serum creatinine (91.6 ± 28.6 vs. 69.6 ± 16.5 μmol/l, P < 0.0003), higher BILAG score (13.6 ± 8.2 vs. 7.2 ± 3.2, P < 0.0001), higher baseline corticosteroid dose (18.3 ± 1.3.3 vs. 8 ± 8 mg/day, P < 0.004), and were more likely to enter the study taking a concomitant immunosuppressive agent (MMF; 50 vs. 22%). There were no quantitative differences in NR and LN serum cytokine levels for most analytes that were within the limits of detection. Eotaxin and soluble TNF receptor II were greater in LN sera ( P = 0.037 and P = 0.022, respectively). Interestingly, IL-17 was not detectable in any LN sample, but was present in 17% of NR sera. LN and NR PBMC proliferated equally well to LPS and PHA, but in response to TT proliferation of NR PBMC was greater than LN PBMC ( P < 0.0001). TT did not induce LN PBMC cytokine production. LPS and PHA induced significant increases in production of 24 of the 38 measured cytokines from PBMC, but there were few differences between LN and NR. LPS-induced IL-7 and IL-12 levels were higher from LN PBMC ( P < 0.02), and PHA induced more IL-5 production by NR PBMC ( P = 0.008). Unexpectedly, no cytokine signature that distinctly separates LN from NR emerged from this survey. This may be due to the greater baseline level of immunosuppression in LN patients, but even with immunosuppression the LN was very active. It is intriguing to speculate that differences, perhaps genetic, in the kidney's response to inflammation, rather than differences in circulating proinflammatory cytokines, determine susceptibility to LN in SLE patients.
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 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 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 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 ».