Elevated aluminum excretion in patients by long-term subcutaneous immunotherapy - A cross-sectional case-control study.
Adjuvant
Aluminum
Biomonitoring
Immunologic desensitization
Risk assessment
Venom hypersensitivity
Journal
International journal of hygiene and environmental health
ISSN: 1618-131X
Titre abrégé: Int J Hyg Environ Health
Pays: Germany
ID NLM: 100898843
Informations de publication
Date de publication:
09 Mar 2024
09 Mar 2024
Historique:
received:
31
10
2023
revised:
19
01
2024
accepted:
06
02
2024
medline:
11
3
2024
pubmed:
11
3
2024
entrez:
10
3
2024
Statut:
aheadofprint
Résumé
Aluminum (Al) adjuvants have been used in vaccines and subcutaneous immunotherapy (SCIT) for decades. Despite indisputable neurotoxic properties of Al, there is no clear evidence of a causal relationship between their use and any neurotoxic side effects. However, recent rat studies have shown an accumulation of Al from adjuvants in tissues, especially in bones. Since the human toxicokinetics of Al-adjuvants are poorly understood, this study aimed to evaluate whether up-dosed or long-term SCIT with Al-coupled extracts leads to increased Al load in humans. This observational cross-sectional case-control study explored Al excretion in hymenoptera venom allergy patients recruited in 2020 before initiation (n = 10) and during ongoing (n = 12) SCIT with Al-based preparations. Urine samples were collected before and 24 h after the SCIT injections and analyzed for aluminum content by using atomic absorption spectrometry. The cumulative administered Al dose was extracted from patient records. Patients receiving long-term immunotherapy were treated between 2.8 and 13.6 years (mean 7.1). Other potential sources of Al exposure were surveyed. Patients who had received Al-coupled immunotherapy for several years showed significantly (p < 0.001) higher Al excretion than the controls at initiation of immunotherapy (mean 18.2 μg/gC vs. 7.9 μg/gC) and predominantly (73%) were above the 95th percentile of the general populations' exposure (>15 μg/gC), however, without reaching levels of toxicological concern (>50 μg/gC). Taking both groups together excreted Al levels correlated with the cumulative administered Al dose from SCIT (linear regression: Al These results suggest a relevant iatrogenic contribution of long-term SCIT to human internal Al burden and potential accumulation. Considering the medical benefits of Al-adjuvants and SCIT a differentiated risk-benefit analysis is needed. For certain scenarios of potential toxicological concern in clinical practice biomonitoring might be advisable.
Sections du résumé
BACKGROUND
BACKGROUND
Aluminum (Al) adjuvants have been used in vaccines and subcutaneous immunotherapy (SCIT) for decades. Despite indisputable neurotoxic properties of Al, there is no clear evidence of a causal relationship between their use and any neurotoxic side effects. However, recent rat studies have shown an accumulation of Al from adjuvants in tissues, especially in bones.
OBJECTIVES
OBJECTIVE
Since the human toxicokinetics of Al-adjuvants are poorly understood, this study aimed to evaluate whether up-dosed or long-term SCIT with Al-coupled extracts leads to increased Al load in humans.
METHODS
METHODS
This observational cross-sectional case-control study explored Al excretion in hymenoptera venom allergy patients recruited in 2020 before initiation (n = 10) and during ongoing (n = 12) SCIT with Al-based preparations. Urine samples were collected before and 24 h after the SCIT injections and analyzed for aluminum content by using atomic absorption spectrometry. The cumulative administered Al dose was extracted from patient records. Patients receiving long-term immunotherapy were treated between 2.8 and 13.6 years (mean 7.1). Other potential sources of Al exposure were surveyed.
RESULTS
RESULTS
Patients who had received Al-coupled immunotherapy for several years showed significantly (p < 0.001) higher Al excretion than the controls at initiation of immunotherapy (mean 18.2 μg/gC vs. 7.9 μg/gC) and predominantly (73%) were above the 95th percentile of the general populations' exposure (>15 μg/gC), however, without reaching levels of toxicological concern (>50 μg/gC). Taking both groups together excreted Al levels correlated with the cumulative administered Al dose from SCIT (linear regression: Al
DISCUSSION
CONCLUSIONS
These results suggest a relevant iatrogenic contribution of long-term SCIT to human internal Al burden and potential accumulation. Considering the medical benefits of Al-adjuvants and SCIT a differentiated risk-benefit analysis is needed. For certain scenarios of potential toxicological concern in clinical practice biomonitoring might be advisable.
Identifiants
pubmed: 38461738
pii: S1438-4639(24)00018-X
doi: 10.1016/j.ijheh.2024.114337
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
114337Informations de copyright
Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Nicola Wagner reports a relationship with ALK-Abelló, Novartis Pharma GmbH, Allergopharma GmbH & Co KG, Sanofi-Aventis Deutschland GmbH, Shire/Takeda, Blueprint, AbbVie Deutschland GmbH & Co KG and with Biocryst that includes: consulting or advisory, funding grants, and speaking and lecture fees.