EXPOSURE TO PER- AND POLYFLUOROALKYL SUBSTANCES (PFAS) AND SYSTEMIC LUPUS ERYTHEMATOSUS: A PILOT STUDY IN THE MICHIGAN LUPUS EPIDEMIOLOGY & SURVEILLANCE (MILES) PROGRAM
Notice bibliographique
Résumé
PV077 / #669 Poster Topic: AS10 - Environment and SLE Background/Purpose Per- and polyfluoroalkyl substances (PFAS), often called “forever chemicals,” are a large class of chemicals found in consumer products and as contaminants in food and drinking water. PFAS are known to be immunotoxic. Evidence supports a link between PFAS and some autoimmune conditions, but their relationship with systemic lupus erythematosus (SLE) risk and disease severity has not been well characterized. This pilot study in women with SLE explored the relationship between serum PFAS levels and disease activity. We hypothesized that higher PFAS levels would be linked to increased disease activity in Black and White women. Methods In serum specimens from 70 female participants with SLE (self-reported race: Black n=35, White n=35) in the Michigan Lupus Epidemiology and Surveillance (MILES) Cohort, we quantified 48 PFAS analytes using isotope dilution and solid-phase extraction followed by liquid chromatography-mass-spectrometry. Disease activity was measured by the Systemic Lupus Activity Questionnaire (SLAQ), a validated patient-reported outcome measure. For PFAS analytes that were detected in ≥40% of participants, we first modeled the relationship between each PFAS concentration and SLAQ score, adjusting for age, race, and BMI. Combining Least Absolute Shrinkage and Selection Operator (LASSO) and expertise knowledge, we selected the most important PFAS features for a multivariable regression, adjusted for covariates, to model PFAS mixtures in all women and stratified by race. Results Among the 48 PFAS measured, 28 were detected in at least 1 serum specimen, and 16 were “commonly detected” in ≥40% of samples. Five PFAS had significantly higher rates of detection (%) or median levels in Black compared to White women. Adjusting for other confounders, 2 of the 16 commonly detected PFAS exhibited statistically significant associations with SLAQ score (p-value <0.05). Perfluorodecanoic acid (PFDA) was positively associated [1.69 unit increase SLAQ per 1-unit increase in standardized PFDA (95% CI 0, 3.37)], and perfluorohexanesulfonic acid (PFHxS) was inversely associated [-1.62 (95% CI -3.23, -0.01)] with SLAQ. We applied LASSO to identify the most important PFAS features relevant to SLAQ and prevent overfitting. Five PFAS, selected by LASSO, were modeled simultaneously with SLAQ. PFDA and perfluoro-n-hexadecanoic acid (PFHxDA) had consistent positive associations in all women and when stratified by race, whereas no significant inverse associations were detected in the mixture analysis (Figure). Figure. Conclusions This pilot study is the first to examine relationships between environmental exposures to immunotoxic PFAS and SLE activity. We observed associations between higher serum concentrations of 2 PFAS – PFDA and PFHxDA – with increased disease activity, measured by SLAQ score. Data suggest that immunotoxicity of PFAS may extend to SLE, a prototypic autoimmune disease.
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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) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,001 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,001 |
| 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 ».