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补偿性 IgM 出手相救:选择性 IgA 缺乏症患者对 MAA-LDL 具有增加的天然 IgM 抗体,且口腔微生物组无变化。

Compensatory IgM to the Rescue: Patients with Selective IgA Deficiency Have Increased Natural IgM Antibodies to MAA-LDL and No Changes in Oral Microbiota.

机构信息

Medical Microbiology and Immunology, Research Unit of Biomedicine, University of Oulu, Oulu, Finland;

Department of Biological and Environmental Science, University of Jyväskylä, Jyväskylä, Finland.

出版信息

Immunohorizons. 2021 Apr 23;5(4):170-181. doi: 10.4049/immunohorizons.2100014.

DOI:10.4049/immunohorizons.2100014
PMID:33893180
Abstract

IgA is the most abundant Ab in the human body. However, most patients with selective IgA deficiency (SIgAD) are asymptomatic. IgM, and to lesser extent IgG Abs, are generally presumed to compensate for the lack of IgA in SIgAD by multiplying and adopting functions of IgA. We used data from the Northern Finland Birth Cohort 1966 to investigate whether SIgAD patients have differences in levels of natural Abs to oxidized epitopes compared with 20 randomly selected healthy controls. First, we screened the saliva and serum samples from the Northern Finland Birth Cohort 1966 cohort ( 1610) for IgA concentration. We detected five IgA-deficient subjects, yielding a prevalence of 0.3%, which is consistent with the general prevalence of 0.25% in the Finnish population. To detect natural Abs, we used malondialdehyde acetaldehyde-low-density lipoprotein (MAA-LDL), an Ag known to bind natural Abs. In this study, we show that natural secretory IgM and IgG Abs to MAA-DL were significantly increased in subjects with SIgAD. Given that secretory IgA is an important part of mucosal immune defense and that, in the gut microbiota, dysbiosis with SIgAD patients has been observed, we characterized the oral bacterial microbiota of the subjects with and without SIgAD using high-throughput 16S rRNA gene sequencing. We found no significant alterations in diversity and composition of the oral microbiota in subjects with SIgAD. Our data suggest that increased levels of secretory natural Abs in patients with SIgAD could be a compensatory mechanism, providing alternative first-line defense against infections and adjusting mucosal milieu to maintain a healthy oral microbiota.

摘要

IgA 是人体内含量最丰富的 Ab。然而,大多数选择性 IgA 缺乏症(SIgAD)患者无症状。通常认为,IgM,以及在较小程度上的 IgG Abs,通过增殖和采用 IgA 的功能来弥补 SIgAD 中 IgA 的缺乏。我们使用来自芬兰北部出生队列 1966 年的数据,调查了 SIgAD 患者与 20 名随机选择的健康对照者相比,其氧化表位天然 Ab 水平是否存在差异。首先,我们筛选了芬兰北部出生队列 1966 年队列(1610 人)的唾液和血清样本,以检测 IgA 浓度。我们检测到 5 名 IgA 缺乏的受试者,患病率为 0.3%,这与芬兰人群的一般患病率 0.25%一致。为了检测天然 Ab,我们使用了已知与天然 Ab 结合的丙二醛乙醛低密度脂蛋白(MAA-LDL)作为 Ag。在这项研究中,我们表明 SIgAD 患者的天然分泌型 IgM 和 IgG 对 MAA-DL 的抗体显著增加。鉴于分泌型 IgA 是黏膜免疫防御的重要组成部分,并且在肠道微生物群中观察到 SIgAD 患者的微生态失调,我们使用高通量 16S rRNA 基因测序对有和没有 SIgAD 的受试者的口腔细菌微生物群进行了特征描述。我们发现 SIgAD 受试者的口腔微生物群多样性和组成没有显著变化。我们的数据表明,SIgAD 患者中分泌型天然 Ab 水平的升高可能是一种代偿机制,提供了针对感染的替代一线防御,并调整黏膜环境以维持健康的口腔微生物群。

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