Addressing Complications of Complement Activation Product Evaluation in Autoimmune Inflammatory Myopathies
Notice bibliographique
Résumé
Objectives Biomarkers are needed for efficient diagnosis and monitoring of autoimmune inflammatory myopathies (AIM). Complement activation products (CAP) reflect the activation state of the complement system, an important mechanism of AIM pathogenesis. However, CAP analysis requires standardized sampling and accurate assay procedures. This study aimed to establish a standardized protocol for measuring blood-based serum CAPs, C3a, C5a, and soluble C5b-9 (sC5b-9) to be utilized in future research studies evaluating novel biomarkers for AIM. Methods Paired plasma (n=21) and serum samples (n=21) from AIM patients, and plasma samples (n=50) from healthy controls (HC), were obtained from the Plasma Services Group (PSG, Moorestown, NJ). Samples were shipped on dry ice, stored at −80°C, and had not undergone any freeze-thaw cycles (non-freeze-thawed [NFT]). Serum samples from AIM patients enrolled in a multi-site Canadian registry were included (n=80) and had undergone 1-3 freeze-thaw (FT) cycles. C3a and C5a concentrations of each sample were measured using meso scale discovery (Meso Scale Diagnostics, Rockville, MD) while sC5b-9 concentrations were measured with an enzyme-linked immunosorbent assay (Quidel Corporation, San Diego, CA). Using t tests, for each CAP we compared the mean concentration of 1) plasma to serum (paired patients who had AIM and have not undergone FT), 2) FT to NFT (unpaired AIM patients and these were serum only), and 3) HC to AIM (NFT plasma samples only). Results When comparing plasma to serum, serum had higher mean concentrations of C3a (mean difference [MD] 7.7 ng/mL [95% confidence interval [CI]: 2.7, 12.8]) and C5a (MD 98.7 ng/mL [95% CI 75, 122.3]) (Table 1). There was no significant difference for sC5b-9. When comparing FT to NFT samples, FT samples had significantly higher C3a (MD 3230.6 ng/mL [95% CI 2919.8, 3541.4]), but lower C5a (MD −96.1 ng/mL [95% CI −108.6, −83.7]). There was no significant difference for sC5b-9. When comparing AIM to HC, HC had significantly lower sC5b-9 mean concentrations than AIM (MD −8228.8 ng/mL [95% CI −10379.7, −6077.9]). There was no difference for C3a between AIM and HC and only a small difference was detected for C5a (MD 3.1 ng/mL [95% CI 0.5, 5.7]). Table 1. Mean concentration of C3a, C5a, and soluble C5b-9 (sC5b-9) for 1) plasma vs. serum from the same autoimmune inflammatory myopathy (AIM) patients with no history of freeze-thaw (non-freeze-thaw, NFT), 2) Freeze-thawed (FT) vs. NFT samples (serum samples from different AIM patients in each group), 3) Healthy controls (HC) vs. AIM (NFT and plasma samples only) Conclusion Comparing the same type of blood specimen and avoiding freeze-thaw cycles are important factors to consider when interpreting CAP levels, particularly for C3a and C5a. Future studies to examine factors that may have contributed to variability, including differences in AIM patient characteristics such as disease subsets and activity are underway.
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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 | 0,003 | 0,004 |
| Méta-épidémiologie (sens strict) | 0,000 | 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 | 0,001 | 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) | 0,000 | 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 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 ».