Cano-Cano Fátima, Lara-Barea Almudena, Cruz-Gómez Álvaro Javier, Martín-Loro Francisco, Gómez-Jaramillo Laura, González-Montelongo María Carmen, Roca-Rodríguez María Mar, Beltrán-Camacho Lucía, Forero Lucía, González-Rosa Javier J, Durán-Ruiz Mª Carmen, Arroba Ana I, Aguilar-Diosdado Manuel
Diabetes Mellitus Laboratory, Institute of Research and Biomedical Innovation of Cadiz (INiBICA), Cádiz, Spain.
Psychology Department, Institute of Research and Biomedical Innovation of Cadiz (INiBICA), University of Cadiz, Cádiz, Spain.
Mol Med. 2025 Feb 3;31(1):36. doi: 10.1186/s10020-025-01084-x.
Interest in the study of type 1 diabetes mellitus (T1DM) and multiple sclerosis (MS) has increased because of their significant negative impact on the patient quality of life and the profound implications for the health care system. Although the clinical symptoms of T1DM differ from those of MS, such as pancreatic β-cell failure in T1DM and demyelination in the central nervous system (CNS) in MS, both pathologies are considered as autoimmune-related diseases with shared pathogenic pathways, which include autophagy, inflammation and degeneration, among others. Considering the challenges in obtaining pancreatic β-cells and CNS tissue from patients with T1DM and MS, respectively, it is fundamental to explore alternative methods for evaluating disease status. Proteomic analysis of peripheral blood mononuclear cells (PBMCs) is an ideal approach for identifying novel and potential biomarkers for both autoimmune diseases.
We conducted a proteomic analysis of PBMCs from patients with T1DM and relapsing remitting Multiple Sclerosis (herein forth MS) patients (n = 9 per condition), using a label-free quantitative proteomics approach. The patients were diagnosed following the American Diabetes Association (ADA) criteria for T1DM and McDonald criteria for MS respectively, and were aged over 18 years and more than 2 years from the onset respectively.
A total of 2476 proteins were differentially expressed in PBMCs from patients with T1DM and MS patients compared with those form healthy controls (H). Predictive analysis highlighted 15 common proteins, up- or downregulated in PBMCs from patients with T1DM and MS patients vs. healthy controls, involved in the immune system activity (BTF3, TTR, CD59, CSTB), diseases of the neuronal system (TTR), signal transduction (STMN1, LAMTOR5), metabolism of nucleotides (RPS21), proteins (TTR, ENAM, CD59, RPS21, SRP9) and RNA (SRSF10, RPS21). In addition, this study revealed both shared and distinct molecular patterns between the two conditions.
Compared with H, patients with T1DM and MS presented a specific expression pattern of common proteins has been identified. This pattern underscores the shared mechanisms involved in their immune responses and neurological complications, alongside dysregulation of the autophagy pathway. Notably, CSTB has emerged as a differential biomarker, distinguishing between these two autoimmune diseases.
1型糖尿病（T1DM）和多发性硬化症（MS）的研究受到越来越多的关注，因为它们对患者生活质量有重大负面影响，并且对医疗保健系统有深远影响。尽管T1DM的临床症状与MS不同，如T1DM中的胰腺β细胞功能衰竭和MS中的中枢神经系统（CNS）脱髓鞘，但这两种疾病都被认为是自身免疫相关疾病，具有共同的致病途径，包括自噬、炎症和变性等。考虑到分别从T1DM和MS患者获取胰腺β细胞和CNS组织存在挑战，探索评估疾病状态的替代方法至关重要。外周血单核细胞（PBMC）的蛋白质组分析是识别这两种自身免疫性疾病新的潜在生物标志物的理想方法。
我们采用无标记定量蛋白质组学方法，对T1DM患者和复发缓解型多发性硬化症（以下简称MS）患者（每种情况n = 9）的PBMC进行了蛋白质组分析。患者分别按照美国糖尿病协会（ADA）的T1DM标准和麦克唐纳MS标准进行诊断，年龄均超过18岁，且发病分别超过2年。
与健康对照（H）相比，T1DM患者和MS患者的PBMC中共有2476种蛋白质表达存在差异。预测分析突出了15种常见蛋白质，在T1DM患者和MS患者的PBMC中相对于健康对照上调或下调，这些蛋白质参与免疫系统活动（BTF3、TTR、CD59、CSTB）、神经系统疾病（TTR）、信号转导（STMN1、LAMTOR5）、核苷酸代谢（RPS21）、蛋白质（TTR、ENAM、CD59、RPS21、SRP9）和RNA（SRSF10、RPS21）。此外，本研究揭示了这两种疾病之间共同和独特的分子模式。
与H相比，已确定T1DM患者和MS患者存在共同蛋白质的特定表达模式。这种模式强调了它们免疫反应和神经并发症中涉及的共同机制，以及自噬途径的失调。值得注意的是，CSTB已成为区分这两种自身免疫性疾病的差异生物标志物。
