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肺炎球菌多糖疫苗可在健康个体和1型糖尿病患者中诱导产生IgG抗A/B血型抗体。

Pneumococcal Polysaccharide Vaccination Elicits IgG Anti-A/B Blood Group Antibodies in Healthy Individuals and Patients with Type I Diabetes Mellitus.

作者信息

Wolfram Wendelin, Sauerwein Kai M T, Binder Christoph J, Eibl-Musil Nicole, Wolf Hermann M, Fischer Michael B

机构信息

Clinic for Blood Group Serology and Transfusion Medicine, Medical University of Vienna , Vienna , Austria.

Immunology Outpatient Clinic , Vienna , Austria.

出版信息

Front Immunol. 2016 Nov 14;7:493. doi: 10.3389/fimmu.2016.00493. eCollection 2016.

Abstract

HYPOTHESIS

Blood group antibodies are natural antibodies that develop early in life in response to cross-reactive environmental antigens in the absence of antigen encounter. Even later in life structural similarities in saccharide composition between environmental antigens such as bacterial polysaccharides and blood group A/B antigens could lead to changes in serum levels, IgM/IgG isotype, and affinity maturation of blood group anti-A/B antibodies. We addressed the question whether immunization with pneumococcal polysaccharide (PnP) vaccine Pneumo 23 Vaccine "Pasteur Merieux" (Pn23) could have such an effect in patients with type I diabetes mellitus (DM I), an autoimmune disease where an aberrant immune response to microbial antigens likely plays a role.

METHODS

Anti-PnP IgM and IgG responses were determined by ELISA, and the DiaMed-ID Micro Typing System was used to screen anti-A/B antibody titer before and after Pn23 immunization in 28 healthy individuals and 16 patients with DM I. In addition, surface plasmon resonance (SPR) technology using the Biacore device and a synthetic blood group A/B trisaccharide as the antigen was applied to investigate IgM and IgG anti-A/B antibodies and to measure antibody binding dynamics.

RESULTS

All healthy individuals and DM I patients responded with anti-PnP IgM and IgG antibody production 4-6 weeks after Pn23 immunization, while no increase in blood group anti-A/B antibody titer was observed when measured by the DiaMed-ID Micro Typing System. Interestingly, isotype-specific testing by SPR technology revealed an increase in blood group anti-A/B IgG, but not IgM, following Pn23 immunization in both patients and controls. No change in binding characteristics of blood group anti-A/B antibodies could be detected following Pn23 vaccination, supporting the assumption of an increase in IgG antibody titer with no or very little affinity maturation.

CONCLUSION

The study provides evidence for epitope sharing between pneumococcal polysaccharides and blood group ABO antigens, which leads to a booster of blood group anti-A/B antibodies of the IgG isotype after Pn23 immunization in healthy individuals. Manifest autoimmunity such as present in DM I patients has no additional effect on the cross-reactive antibody response against pneumococcal polysaccharides and blood group antigens.

摘要

假说

血型抗体是天然抗体,在生命早期,在未接触抗原的情况下,因对交叉反应性环境抗原产生应答而形成。即使在生命后期,诸如细菌多糖等环境抗原与A/B血型抗原之间在糖类组成上的结构相似性,也可能导致血型抗A/B抗体的血清水平、IgM/IgG同种型以及亲和力成熟度发生变化。我们探讨了用肺炎球菌多糖(PnP)疫苗“巴斯德梅里埃”肺炎23价疫苗(Pn23)进行免疫接种,是否会对I型糖尿病(DM I)患者产生这样的影响,I型糖尿病是一种自身免疫性疾病,对微生物抗原的异常免疫反应可能在其中起作用。

方法

通过酶联免疫吸附测定(ELISA)确定抗PnP IgM和IgG应答,并使用DiaMed-ID微定型系统,在28名健康个体和16名DM I患者中,筛查Pn23免疫接种前后的抗A/B抗体效价。此外,应用表面等离子体共振(SPR)技术,使用Biacore设备并以合成的A/B血型三糖作为抗原,来研究IgM和IgG抗A/B抗体,并测量抗体结合动力学。

结果

所有健康个体和DM I患者在Pn23免疫接种后4 - 6周,均产生了抗PnP IgM和IgG抗体,而用DiaMed-ID微定型系统检测时,未观察到血型抗A/B抗体效价升高。有趣的是,SPR技术的同种型特异性检测显示,在患者和对照组中,Pn23免疫接种后,血型抗A/B IgG升高,但IgM未升高。Pn23疫苗接种后,未检测到血型抗A/B抗体结合特性的变化,这支持了IgG抗体效价升高但亲和力成熟度无或极低的假设。

结论

该研究为肺炎球菌多糖与ABO血型抗原之间存在表位共享提供了证据,这导致在健康个体中,Pn23免疫接种后,IgG同种型的血型抗A/B抗体增强。像DM I患者中存在的明显自身免疫,对针对肺炎球菌多糖和血型抗原的交叉反应性抗体应答没有额外影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a8/5108245/bd6849f9a444/fimmu-07-00493-g001.jpg

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