Department of Rheumatology and Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Immunol. 2022 Nov 22;13:1026921. doi: 10.3389/fimmu.2022.1026921. eCollection 2022.
Immunoglobulin G4-related disease (IgG4-RD) is a newly defined disease entity, with great heterogeneity among IgG4-RD subgroups with different organ involvement patterns. Identification of the proteomic characteristics of IgG4-RD subgroups will be critical for the understanding of the pathogenic mechanisms of IgG4-RD.
In this study, we performed proteomic analysis using Tandem Mass Tags (TMT) technology with "high field" mass analyzer with improved resolution and sequencing speed to investigate the proteomic profile of saliva and plasma samples from ten untreated IgG4-RD patients and five healthy controls (HCs). Differentially expressed proteins (DEPs) were identified by "t test" function in R package. Functional enrichment analysis was used to investigate pathways enriched in IgG4-RD samples.
Most salivary DEPs identified in IgG4-RD patients compared with HCs were mainly enriched in neutrophil mediated GO bioprocess. Within the comparisons between four IgG4-RD subgroups, more DEPs were identified in the comparison of Mikulicz group and Head and neck group. Among four subgroups of IgG4-RD, Head and neck group showed the most distinctive proteomic expression pattern when compared with HCs. Moreover, "Neutrophil mediated process" related GO bioprocess was commonly identified between comparisons of Mikulicz group and Head and neck group, Head and neck group and Retroperitoneal aorta group, Head and neck group and HCs, IgG4-RD patients with saliva gland involvement and those without saliva gland involvement. Key DEPs that involved in this GO bioprocess were identified. Besides, we performed proteomic analysis for plasma samples between ten IgG4-RD and five HCs and there were several DEPs identified overlapped in saliva and plasma.
We identified multiple processes/factors and several signaling pathways in saliva that may be involved in the IgG4-RD pathogenesis.
免疫球蛋白 G4 相关疾病（IgG4-RD）是一种新定义的疾病实体，不同器官受累模式的 IgG4-RD 亚组之间存在很大的异质性。鉴定 IgG4-RD 亚组的蛋白质组学特征对于理解 IgG4-RD 的发病机制至关重要。
在这项研究中，我们使用串联质量标签（TMT）技术进行蛋白质组学分析，该技术采用“高场”质量分析仪，具有提高的分辨率和测序速度，以研究来自 10 名未经治疗的 IgG4-RD 患者和 5 名健康对照（HC）的唾液和血浆样本的蛋白质组学特征。通过 R 包中的“t 检验”功能鉴定差异表达蛋白（DEPs）。功能富集分析用于研究 IgG4-RD 样本中富集的途径。
与 HCs 相比，IgG4-RD 患者唾液中鉴定的大多数 DEPs 主要富集在中性粒细胞介导的 GO 生物过程中。在四个 IgG4-RD 亚组之间的比较中，Mikulicz 组和头颈部组之间鉴定出更多的 DEPs。在四个 IgG4-RD 亚组中，与 HCs 相比，头颈部组表现出最独特的蛋白质组学表达模式。此外，“中性粒细胞介导的过程”相关 GO 生物过程在 Mikulicz 组与头颈部组、头颈部组与腹膜后主动脉组、头颈部组与 HCs、有唾液腺受累的 IgG4-RD 患者与无唾液腺受累的 IgG4-RD 患者之间的比较中经常被鉴定出来。鉴定出涉及此 GO 生物过程的关键 DEPs。此外，我们在十个 IgG4-RD 和五个 HCs 之间进行了血浆样本的蛋白质组学分析，发现几个在唾液和血浆中都鉴定出的 DEPs 存在重叠。
我们在唾液中鉴定出多个可能参与 IgG4-RD 发病机制的过程/因素和几个信号通路。
