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个体人血清中独特的抗碳水化合物抗体库。

Unique repertoire of anti-carbohydrate antibodies in individual human serum.

机构信息

Department of Surgery, Harvard Medical School, Beth Israel Deaconess Medical Center, National Center for Functional Glycomics, CLS 11087 - 3 Blackfan Circle, Boston, MA, 02115, USA.

Department of Biology, Institute of Microbiology, ETH Zurich, 8093, Zurich, Switzerland.

出版信息

Sci Rep. 2020 Sep 22;10(1):15436. doi: 10.1038/s41598-020-71967-y.

DOI:10.1038/s41598-020-71967-y
PMID:32963315
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7509809/
Abstract

Humoral immunity to pathogens and other environmental challenges is paramount to maintain normal health, and individuals lacking or unable to make antibodies are at risk. Recent studies indicate that many human protective antibodies are against carbohydrate antigens; however, little is known about repertoires and individual variation of anti-carbohydrate antibodies in healthy individuals. Here we analyzed anti-carbohydrate antibody repertoires (ACARs) of 105 healthy individual adult donors, aged 20-60 from different ethnic backgrounds to explore variations in antibodies, as defined by binding to glycan microarrays and by affinity purification. Using microarrays that contained > 1,000 glycans, including antigens from animal cells and microbes, we profiled the IgG and IgM ACARs from all donors. Each donor expressed many ACAs, but had a relatively unique ACAR, which included unanticipated antibodies to carbohydrate antigens not well studied, such as chitin oligosaccharides, Forssman-related antigens, globo-type antigens, and bacterial glycans. We also saw some expected antibodies to ABO(H) blood group and α-Gal-type antigens, although these also varied among individuals. Analysis suggests differences in ACARs are associated with ethnicity and age. Thus, each individual ACAR is relatively unique, suggesting that individualized information could be useful in precision medicine for predicting and monitoring immune health and resistance to disease.

摘要

体液免疫对于病原体和其他环境挑战至关重要,可维持正常健康,而缺乏或无法产生抗体的个体则面临风险。最近的研究表明,许多人类保护性抗体针对的是碳水化合物抗原;然而,对于健康个体中抗碳水化合物抗体的 repertoire 和个体差异知之甚少。在这里,我们分析了来自不同种族背景的 105 名年龄在 20-60 岁的健康个体成人供体的抗碳水化合物抗体 repertoire (ACAR),以探索抗体的变化,这些变化由与聚糖微阵列的结合和亲和纯化来定义。使用包含>1000 种聚糖的微阵列,包括来自动物细胞和微生物的抗原,我们对所有供体的 IgG 和 IgM ACAR 进行了分析。每个供体都表达了许多 ACAs,但具有相对独特的 ACAR,其中包括对尚未深入研究的碳水化合物抗原的意外抗体,例如几丁寡糖、Forssman 相关抗原、globotype 抗原和细菌聚糖。我们还观察到一些对 ABO(H)血型和α-Gal 型抗原的预期抗体,尽管这些抗体在个体之间也存在差异。分析表明,ACAR 的差异与种族和年龄有关。因此,每个个体的 ACAR 相对独特,这表明个体化信息可能有助于精准医学,用于预测和监测免疫健康和对疾病的抵抗力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a2d/7509809/fb9f606f74cb/41598_2020_71967_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a2d/7509809/31c07ef8560d/41598_2020_71967_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a2d/7509809/ef9f32691857/41598_2020_71967_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a2d/7509809/fb9f606f74cb/41598_2020_71967_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a2d/7509809/f7dc55056fa7/41598_2020_71967_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a2d/7509809/08dfe61ec33a/41598_2020_71967_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a2d/7509809/13be6b237fcd/41598_2020_71967_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a2d/7509809/a2f6a513bf76/41598_2020_71967_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a2d/7509809/a42e97dd18bc/41598_2020_71967_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a2d/7509809/31c07ef8560d/41598_2020_71967_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a2d/7509809/ef9f32691857/41598_2020_71967_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a2d/7509809/fb9f606f74cb/41598_2020_71967_Fig8_HTML.jpg

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