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高通量 RNA 测序揭示 IgG4 相关疾病活动期的独特基因特征。

High-throughput RNA sequencing reveals distinct gene signatures in active IgG4-related disease.

机构信息

MedImmune, Gaithersburg, MD, 20878, USA.

Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, 100044, China.

出版信息

Sci Rep. 2017 Dec 14;7(1):17567. doi: 10.1038/s41598-017-17602-9.

DOI:10.1038/s41598-017-17602-9
PMID:29242501
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5730556/
Abstract

We aimed to characterize the molecular differences and effects from prednisone treatment among IgG4-related disease with salivary gland lesions (RD-SG), without SG lesions (RD-nonSG), and IgG4-related retroperitoneal fibrosis (RF). RNA sequencing was conducted on blood from 25 RD-SG, 11 RD-nonSG, 3 RF and 10 control subjects. Among these, 8 RD-nonSG and 12 RD-SG patients were subjected to treatment with prednisone and/or glucocorticoid-sparing agents. Six RD patients had a longitudinal time point. The mRNA levels of IgG4 and IgE, genes specific for Th2 cells, eosinophils, and neutrophils were over-expressed in RD-SG and RD-nonSG. A B-cell signature was suppressed in patients group versus controls, while Th1, Th2, Treg, and eosinophil gene signatures were increased in patients without treatment. Interestingly, Tfh genes and B cell signature were decreased at flare disease state. Prednisone treatment led to increased neutrophil, but decreased Treg signatures. Serum IgG4 levels correlated with the eosinophil and neutrophil gene signatures in RD-SG patients, and with a B cell signature in only RD-nonSG patients. IgG4, IgE, and cell-specific signatures are regulated in patients, suggesting the imbalance of immune and inflammatory cells in IgG4-related disease. Prednisone treatment selectively modulates Treg, eosinophil, and neutrophil signatures.

摘要

我们旨在描述 IgG4 相关疾病伴唾液腺病变（RD-SG）、无唾液腺病变（RD-nonSG）和 IgG4 相关腹膜后纤维化（RF）患者之间的分子差异和泼尼松治疗的效果。对 25 例 RD-SG、11 例 RD-nonSG、3 例 RF 和 10 例对照患者的血液进行了 RNA 测序。其中，8 例 RD-nonSG 和 12 例 RD-SG 患者接受了泼尼松和/或糖皮质激素保留剂治疗。6 例 RD 患者有纵向时间点。在 RD-SG 和 RD-nonSG 患者中，IgG4 和 IgE 的 mRNA 水平以及 Th2 细胞、嗜酸性粒细胞和中性粒细胞的基因特异性表达上调。与对照组相比，患者组的 B 细胞特征受到抑制，而未经治疗的患者中 Th1、Th2、Treg 和嗜酸性粒细胞基因特征增加。有趣的是，在疾病活动期，Tfh 基因和 B 细胞特征减少。泼尼松治疗导致中性粒细胞增加，但 Treg 特征减少。RD-SG 患者的血清 IgG4 水平与嗜酸性粒细胞和中性粒细胞基因特征相关，而仅在 RD-nonSG 患者中与 B 细胞特征相关。IgG4、IgE 和细胞特异性特征在患者中受到调节，提示 IgG4 相关疾病中免疫和炎症细胞失衡。泼尼松治疗选择性调节 Treg、嗜酸性粒细胞和中性粒细胞特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2e1/5730556/98f36fcfab46/41598_2017_17602_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2e1/5730556/13facf247917/41598_2017_17602_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2e1/5730556/8079e13643e5/41598_2017_17602_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2e1/5730556/98f36fcfab46/41598_2017_17602_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2e1/5730556/13facf247917/41598_2017_17602_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2e1/5730556/8c86cafa93ca/41598_2017_17602_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2e1/5730556/92f600ba6bf4/41598_2017_17602_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2e1/5730556/fc6c5fa00d4c/41598_2017_17602_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2e1/5730556/8079e13643e5/41598_2017_17602_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2e1/5730556/98f36fcfab46/41598_2017_17602_Fig6_HTML.jpg

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