Elevated aluminum excretion in patients by long-term subcutaneous immunotherapy – A cross-sectional case-control study

IF 4.5 2区 医学 Q1 INFECTIOUS DISEASES
Julia Hiller , Thomas Göen , Hans Drexler , Carola Berking , Nicola Wagner
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引用次数: 0

Abstract

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

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

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

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: Alurine = 8.258 + 0.133*Alcum; p = 0.001).

Discussion

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.

Abstract Image

长期接受皮下免疫疗法的患者铝排泄量升高--一项横断面病例对照研究
背景铝(Al)佐剂用于疫苗和皮下免疫疗法(SCIT)已有几十年的历史。尽管铝具有无可争议的神经毒性,但没有明确证据表明使用铝佐剂与任何神经毒副作用之间存在因果关系。这项观察性横断面病例对照研究探讨了 2020 年招募的膜翅目毒液过敏患者在开始(10 人)和持续(12 人)使用铝基制剂进行 SCIT 前的铝排泄情况。在注射 SCIT 之前和之后 24 小时收集尿液样本,并使用原子吸收光谱法分析铝含量。从患者的病历中提取出累积的铝剂量。长期接受免疫疗法的患者接受治疗的时间从 2.8 年到 13.6 年不等(平均为 7.1 年)。结果显示,接受了数年铝耦合免疫疗法的患者在开始接受免疫疗法时的铝排泄量(平均 18.2 μg/gC vs. 7.9 μg/gC)明显高于对照组(p <0.001),且主要(73%)高于普通人群暴露量的第 95 百分位数(15 μg/gC),但未达到毒理学关注的水平(50 μg/gC)。讨论这些结果表明,长期使用 SCIT 会对人体内部的铝负荷和潜在累积产生相关的先天性影响。考虑到铝佐剂和 SCIT 的医疗益处,需要进行有区别的风险效益分析。对于临床实践中某些潜在的毒理学问题,生物监测可能是可取的。
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来源期刊
CiteScore
11.50
自引率
5.00%
发文量
151
审稿时长
22 days
期刊介绍: The International Journal of Hygiene and Environmental Health serves as a multidisciplinary forum for original reports on exposure assessment and the reactions to and consequences of human exposure to the biological, chemical, and physical environment. Research reports, short communications, reviews, scientific comments, technical notes, and editorials will be peer-reviewed before acceptance for publication. Priority will be given to articles on epidemiological aspects of environmental toxicology, health risk assessments, susceptible (sub) populations, sanitation and clean water, human biomonitoring, environmental medicine, and public health aspects of exposure-related outcomes.
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