Defective formation of IgA memory B cells, Th1 and Th17 cells in symptomatic patients with selective IgA deficiency.,Clinical & Translational Immunology

当前位置： X-MOL 学术 › Clin. Transl. Immunol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Defective formation of IgA memory B cells, Th1 and Th17 cells in symptomatic patients with selective IgA deficiency.
Clinical & Translational Immunology ( IF 4.6 ) Pub Date : 2020-04-29 , DOI: 10.1002/cti2.1130
Christina Grosserichter-Wagener ₁ , Alexander Franco-Gallego ₂ , Fatemeh Ahmadi ₁ , Marcela Moncada-Vélez ₂ , Virgil Ash Dalm _{1,

3} , Jessica Lineth Rojas ₂ , Julio César Orrego ₂ , Natalia Correa Vargas ₂ , Lennart Hammarström ₄ , Marco Wj Schreurs ₁ , Willem A Dik ₁ , P Martin van Hagen _{1,

3} , Louis Boon ₅ , Jacques Jm van Dongen _{1,

6} , Mirjam van der Burg _{1,

7} , Qiang Pan-Hammarström ₄ , José L Franco ₂ , Menno C van Zelm _{1,

8,

9}

Affiliation

Objective Selective IgA deficiency (sIgAD) is the most common primary immunodeficiency in Western countries. Patients can suffer from recurrent infections and autoimmune diseases because of a largely unknown aetiology. To increase insights into the pathophysiology of the disease, we studied memory B and T cells and cytokine concentrations in peripheral blood. Methods We analysed 30 sIgAD patients (12 children, 18 adults) through detailed phenotyping of peripheral B-cell, CD8+ T-cell and CD4+ T-cell subsets, sequence analysis of IGA and IGG transcripts, in vitro B-cell activation and blood cytokine measurements. Results All patients had significantly decreased numbers of T-cell-dependent (TD; CD27+) and T-cell-independent (TI; CD27-) IgA memory B cells and increased CD21low B-cell numbers. IgM+IgD- memory B cells were decreased in children and normal in adult patients. IGA and IGG transcripts contained normal SHM levels. In sIgAD children, IGA transcripts more frequently used IGA2 than controls (58.5% vs. 25.1%), but not in adult patients. B-cell activation after in vitro stimulation was normal. However, adult sIgAD patients exhibited increased blood levels of TGF-β1, BAFF and APRIL, whereas they had decreased Th1 and Th17 cell numbers. Conclusion Impaired IgA memory formation in sIgAD patients is not due to a B-cell activation defect. Instead, decreased Th1 and Th17 cell numbers and high blood levels of BAFF, APRIL and TGF-β1 might reflect disturbed regulation of IgA responses in vivo.These insights into B-cell extrinsic immune defects suggest the need for a broader immunological focus on genomics and functional analyses to unravel the pathogenesis of sIgAD.

中文翻译：

选择性 IgA 缺乏症患者中 IgA 记忆 B 细胞、Th1 和 Th17 细胞的缺陷形成。

目的选择性IgA缺乏症（sIgAD）是西方国家最常见的原发性免疫缺陷病。由于很大程度上未知的病因，患者可能患有反复感染和自身免疫性疾病。为了增加对该疾病病理生理学的了解，我们研究了外周血中的记忆 B 和 T 细胞以及细胞因子浓度。方法我们通过外周 B 细胞、CD8+ T 细胞和 CD4+ T 细胞亚群的详细表型分析、IGA 和 IGG 转录本的序列分析、体外 B 细胞活化和血液细胞因子分析了 30 名 sIgAD 患者（12 名儿童，18 名成人）测量。结果所有患者的 T 细胞依赖性（TD；CD27+）和 T 细胞非依赖性（TI；CD27-）IgA 记忆 B 细胞数量显着减少，CD21low B 细胞数量增加。IgM+IgD-记忆 B 细胞在儿童中减少，在成人患者中正常。IGA 和 IGG 转录本包含正常的 SHM 水平。在 sIgAD 儿童中，IGA 转录本比对照组更频繁地使用 IGA2（58.5% 对 25.1%），但在成人患者中则不然。体外刺激后的 B 细胞活化正常。然而，成年 sIgAD 患者的血液中 TGF-β1、BAFF 和 APRIL 水平升高，而 Th1 和 Th17 细胞数量减少。结论 sIgAD 患者 IgA 记忆形成受损不是由于 B 细胞活化缺陷。相反，Th1 和 Th17 细胞数量减少以及 BAFF、APRIL 和 TGF-β1 的高血液水平可能反映了体内 IgA 反应的失调调节。

更新日期：2020-04-29

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文