Identification of TRAPPC4 as a Key Autoantigen in Immune-Related Pancytopenia: Epitope Characterization and Immune Activation Mechanisms.

IF 1.5 4区医学 Q3 HEMATOLOGY

Turkish Journal of Hematology Pub Date : 2025-01-17 DOI:10.4274/tjh.galenos.2025.2024.0365

Shanfeng Hao, Yang Zhang, Na Xiao, Zonghong Shao

{"title":"Identification of TRAPPC4 as a Key Autoantigen in Immune-Related Pancytopenia: Epitope Characterization and Immune Activation Mechanisms.","authors":"Shanfeng Hao, Yang Zhang, Na Xiao, Zonghong Shao","doi":"10.4274/tjh.galenos.2025.2024.0365","DOIUrl":null,"url":null,"abstract":"Objective: Immune-related pancytopenia (IRP) is characterized by autoantibody-mediated destruction or suppression of bone marrow cells, leading to pancytopenia. This study aimed to explore the role of TRAPPC4 (trafficking protein particle complex subunit 4) as a key autoantigen in IRP, including epitope identification and immune activation mechanisms.Methods: A total of 90 participants were included in the study, divided into four groups: 30 newly diagnosed IRP patients, 25 IRP remission patients, 20 patients with control hematologic conditions (severe aplastic anemia [SAA] and myelodysplastic syndrome [MDS]), and 15 healthy controls. TRAPPC4 was identified using affinity screening with a phage random peptide library and confirmed with ELISPOT and epitope prediction software. TRAPPC4 expression in bone marrow cells and serum antibody titers was assessed via flow cytometry, ELISA, and real-time PCR. Immune cell profiling of peripheral blood mononuclear cells (PBMNCs) was conducted using flow cytometry.Results: TRAPPC4 was overexpressed on CD34+ bone marrow hematopoietic progenitor cells in newly diagnosed IRP patients compared to remission patients, disease controls (SAA and MDS), and healthy controls, with no significant differences observed in CD15+ granulocytes or CD235a+ nucleated red blood cells. The epitope peptide YTADGKEVLEYLG activated Th2 cells, as confirmed by ELISPOT. Newly diagnosed IRP patients exhibited elevated TRAPPC4 mRNA and protein levels in bone marrow mononuclear cells and higher serum antibody titers compared with controls. Immune profiling revealed increased CD19+ and CD5+CD19+ B lymphocytes in IRP patients.Conclusion: TRAPPC4 was found as a key autoantigen in IRP, along with CD34+ cells as primary targets of autoantibody attacks. The identification of TRAPPC4 and its epitope provided insights into IRP pathogenesis and suggested potential diagnostic and therapeutic strategies.","PeriodicalId":23362,"journal":{"name":"Turkish Journal of Hematology","volume":" ","pages":""},"PeriodicalIF":1.5000,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Turkish Journal of Hematology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4274/tjh.galenos.2025.2024.0365","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"HEMATOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Objective: Immune-related pancytopenia (IRP) is characterized by autoantibody-mediated destruction or suppression of bone marrow cells, leading to pancytopenia. This study aimed to explore the role of TRAPPC4 (trafficking protein particle complex subunit 4) as a key autoantigen in IRP, including epitope identification and immune activation mechanisms.

Methods: A total of 90 participants were included in the study, divided into four groups: 30 newly diagnosed IRP patients, 25 IRP remission patients, 20 patients with control hematologic conditions (severe aplastic anemia [SAA] and myelodysplastic syndrome [MDS]), and 15 healthy controls. TRAPPC4 was identified using affinity screening with a phage random peptide library and confirmed with ELISPOT and epitope prediction software. TRAPPC4 expression in bone marrow cells and serum antibody titers was assessed via flow cytometry, ELISA, and real-time PCR. Immune cell profiling of peripheral blood mononuclear cells (PBMNCs) was conducted using flow cytometry.

Results: TRAPPC4 was overexpressed on CD34+ bone marrow hematopoietic progenitor cells in newly diagnosed IRP patients compared to remission patients, disease controls (SAA and MDS), and healthy controls, with no significant differences observed in CD15+ granulocytes or CD235a+ nucleated red blood cells. The epitope peptide YTADGKEVLEYLG activated Th2 cells, as confirmed by ELISPOT. Newly diagnosed IRP patients exhibited elevated TRAPPC4 mRNA and protein levels in bone marrow mononuclear cells and higher serum antibody titers compared with controls. Immune profiling revealed increased CD19+ and CD5+CD19+ B lymphocytes in IRP patients.

Conclusion: TRAPPC4 was found as a key autoantigen in IRP, along with CD34+ cells as primary targets of autoantibody attacks. The identification of TRAPPC4 and its epitope provided insights into IRP pathogenesis and suggested potential diagnostic and therapeutic strategies.

查看原文本刊更多论文

TRAPPC4作为免疫相关性全细胞减少症关键自身抗原的鉴定：表位表征和免疫激活机制。

目的：免疫相关性全细胞减少症（IRP）的特点是自身抗体介导的骨髓细胞破坏或抑制，导致全细胞减少。本研究旨在探讨转运蛋白颗粒复合物亚单位4 （TRAPPC4）作为关键自身抗原在IRP中的作用，包括表位鉴定和免疫激活机制。方法：共纳入90例受试者，分为4组：新诊断的IRP患者30例，IRP缓解患者25例，血液学正常（严重再生障碍性贫血[SAA]和骨髓增生异常综合征[MDS]）患者20例，健康对照15例。通过噬菌体随机肽库亲和筛选鉴定TRAPPC4，并通过ELISPOT和表位预测软件进行确认。通过流式细胞术、ELISA和实时荧光定量PCR检测骨髓细胞中TRAPPC4的表达和血清抗体滴度。采用流式细胞术对外周血单核细胞（PBMNCs）进行免疫细胞谱分析。结果：在新诊断的IRP患者中，与缓解患者、疾病对照组（SAA和MDS）和健康对照组相比，TRAPPC4在CD34+骨髓造血祖细胞上过表达，而在CD15+粒细胞或CD235a+有核红细胞上无显著差异。表位肽YTADGKEVLEYLG激活Th2细胞，经ELISPOT证实。与对照组相比，新诊断的IRP患者骨髓单核细胞中TRAPPC4 mRNA和蛋白水平升高，血清抗体滴度更高。免疫分析显示IRP患者的CD19+和CD5+CD19+ B淋巴细胞增加。结论：TRAPPC4是IRP的关键自身抗原，与CD34+细胞一起是自身抗体攻击的主要靶点。TRAPPC4及其表位的鉴定为IRP的发病机制提供了新的见解，并提出了潜在的诊断和治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Turkish Journal of Hematology HEMATOLOGY-

CiteScore

2.90

自引率

3.80%

发文量

审稿时长

1 months

期刊介绍： The Turkish Journal of Hematology is published quarterly (March, June, September, and December) by the Turkish Society of Hematology. It is an independent, non-profit peer-reviewed international English-language periodical encompassing subjects relevant to hematology. The Editorial Board of The Turkish Journal of Hematology adheres to the principles of the World Association of Medical Editors (WAME), International Council of Medical Journal Editors (ICMJE), Committee on Publication Ethics (COPE), Consolidated Standards of Reporting Trials (CONSORT) and Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). The aim of The Turkish Journal of Hematology is to publish original hematological research of the highest scientific quality and clinical relevance. Additionally, educational material, reviews on basic developments, editorial short notes, images in hematology, and letters from hematology specialists and clinicians covering their experience and comments on hematology and related medical fields as well as social subjects are published. As of December 2015, The Turkish Journal of Hematology does not accept case reports. Important new findings or data about interesting hematological cases may be submitted as a brief report.