Volume 14 Issue 5
Sep.  2023
Turn off MathJax
Article Contents
WU Ziyan, FENG Futai, LI Haolong, XU Honglin, ZHANG Shulan, LI Yongzhe. Quantitative Analysis of Mitochondrial Damage in T Lymphocytes from Patients with Autoimmune Diseases and Evaluation of Its Clinical Value[J]. Medical Journal of Peking Union Medical College Hospital, 2023, 14(5): 991-998. doi: 10.12290/xhyxzz.2023-0256
Citation: WU Ziyan, FENG Futai, LI Haolong, XU Honglin, ZHANG Shulan, LI Yongzhe. Quantitative Analysis of Mitochondrial Damage in T Lymphocytes from Patients with Autoimmune Diseases and Evaluation of Its Clinical Value[J]. Medical Journal of Peking Union Medical College Hospital, 2023, 14(5): 991-998. doi: 10.12290/xhyxzz.2023-0256

Quantitative Analysis of Mitochondrial Damage in T Lymphocytes from Patients with Autoimmune Diseases and Evaluation of Its Clinical Value

doi: 10.12290/xhyxzz.2023-0256
Funds:

National Key Research and Development Program of China 2018YFE0207300

National Natural Science Foundation of China 81871302

National High Level Hospital Clinical Research Funding 2022-PUMCH-B-124

More Information
  • Corresponding author: LI Yongzhe, E-mail: yongzhelipumch@126.com
  • Received Date: 2023-03-27
  • Accepted Date: 2023-04-21
  • Publish Date: 2023-09-30
  •   Objective  To evaluate the mitochondrial damage of peripheral blood T lymphocytes in patients with autoimmune diseases (AID) and provide insights for etiological research.  Methods  Clinical data were retrospectively collected from the AID patients treated at the Peking Union Medical College Hospital from March 2023 to April 2023 and from a population that was physically healthy during the same period. Based on the ratio of peripheral blood helper T cells (Th) to cytotoxic T cells (Tc), the AID patients were divided into an immunodeficiency subgroup and an immunocompetent subgroup. Flow cytometry was used to assess the mitochondrial damage of T lymphocytes in the AID patients, with the percentage of cells showing low mitochondrial membrane potential (MMP-low%) as an indicator of mitochondrial dysfunction, and its correlation with AID was analyzed.  Results  A total of 70 AID patients and 20 healthy individuals who met the inclusion and exclusion criteria were included. Among the AID patients, there were 20 immunodeficient cases (Th/Tc ratio < 0.70) and 50 immunocompetent cases (Th/Tc ratio ≥0.70); 33 patients had systemic lupus erythematosus (SLE), 19 had rheumatoid arthritis (RA), and 18 had Sjögren syndrome (SS). The percentage of CD3+ T lymphocytes showing low mitochondrial membrane potential (T MMP-low%), CD3+CD4+ T lymphocytes showing low mitochondrial membrane potential (Th MMP-low%), and CD3+CD8+ T lymphocytes showing low mitochondrial membrane potential (Tc MMP-low%) in SLE, RA, and SS patients were all lower than those in healthy individuals (all P < 0.05). In the AID patients, the percentages of T MMP-low%, Th MMP-low%, and Tc MMP-low% in both the immunodeficient subgroup and immunocompetent subgroup were lower than those in healthy individuals (P < 0.05). Compared to the immunocompetent subgroup, the immunodeficient subgroup showed a decreasing trend in the percentages of T MMP-low%, Th MMP-low%, and Tc MMP-low%, but the differences were not statistically significant (all P > 0.05). Spearman correlation analysis showed that among the mitochondrial damage indicators, only the Th MMP-low%/Tc MMP-low% ratio was correlated with the immune function (Th/Tc ratio) of the AID patients (r=-0.39, P=0.001). The receiver operating characteristic curve showed that Tc MMP-low%, Tc MMP-low%, and Th MMP-low% all had good performance in identifying AID, with respective areas under the curve of 0.83(95% CI: 0.74-0.92), 0.82(95% CI: 0.73-0.92), and 0.77(95% CI: 0.67-0.88), respectively.  Conclusions  Peripheral blood T lymphocytes in AID patients have varying degrees of mitochondrial damage, especially in immunodeficient individuals. Mitochondrial damage-related indicators of T lymphocytes may serve as molecular markers for auxiliary diagnosis of AID.
  • loading
  • [1] Pisetsky DS. Pathogenesis of autoimmune disease[J]. Nat Rev Nephrol, 2023, 19: 509-524.
    [2] Aringer M, Costenbader K, Daikh D, et al. 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythe-matosus[J]. Arthritis Rheumatol, 2019, 71: 1400-1412. doi:  10.1002/art.40930
    [3] Kay J, Upchurch KS. ACR/EULAR 2010 rheumatoid arthritis classification criteria[J]. Rheumatology, 2012, 51: vi5-vi9. doi:  10.1093/rheumatology/ker193
    [4] Shiboski CH, Shiboski SC, Seror R, et al. 2016 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Primary Sjögren's Syndrome: A Consensus and Data-Driven Methodology Involving Three International Patient Cohorts[J]. Arthritis Rheumatol, 2017, 69: 35-45. doi:  10.1002/art.39859
    [5] Soriano BL, Brenner D. Metabolism and epigenetics at the heart of T cell function[J]. Trends Immunol, 2023, 44: 231-244. doi:  10.1016/j.it.2023.01.002
    [6] Becker YLC, Duvvuri B, Fortin PR, et al. The role of mitochondria in rheumatic diseases[J]. Nat Rev Rheumatol, 2022, 18: 621-640. doi:  10.1038/s41584-022-00834-z
    [7] Chen PM, Tsokos GC. Mitochondria in the Pathogenesis of Systemic Lupus Erythematosus[J]. Curr Rheumatol Rep, 2022, 24: 88-95. doi:  10.1007/s11926-022-01063-9
    [8] Clayton SA, MacDonald L, Kurowska SM, et al. Mitochondria as Key Players in the Pathogenesis and Treatment of Rheumatoid Arthritis[J]. Front Immunol, 2021, 12: 673916. doi:  10.3389/fimmu.2021.673916
    [9] Faas MM, de Vos P. Mitochondrial function in immune cells in health and disease[J]. Biochim Biophys Acta Mol Basis Dis, 2020, 1866: 165845. doi:  10.1016/j.bbadis.2020.165845
    [10] Jiao Y, Yan Z, Yang A. Mitochondria in innate immunity signaling and its therapeutic implications in autoimmune diseases[J]. Clin Exp Immunol, 2023, 14: 1160035.
    [11] Saadh MJ, Kazemi K, Khorramdelazad H, et al. Role of T cells in the pathogenesis of systemic lupus erythematous: Focus on immunometabolism dysfunctions[J]. Int Immunopharmacol, 2023, 119: 110246. doi:  10.1016/j.intimp.2023.110246
    [12] Shu P, Liang H, Zhang J, et al. Reactive oxygen species formation and its effect on CD4(+) T cell-mediated inflammation[J]. Front Immunol, 2023, 14: 1199233. doi:  10.3389/fimmu.2023.1199233
    [13] Quintero GDC, Muñoz UM, Vásquez G. Mitochondria as a key player in systemic lupus erythematosus[J]. Autoimmunity, 2022, 55: 497-505. doi:  10.1080/08916934.2022.2112181
    [14] Chávez MD, Tse HM. Targeting Mitochondrial-Derived Reactive Oxygen Species in T Cell-Mediated Autoimmune Diseases[J]. Front Immunol, 2021, 12: 703972. doi:  10.3389/fimmu.2021.703972
    [15] Weyand CM, Wu B, Huang T, et al. Mitochondria as disease-relevant organelles in rheumatoid arthritis[J]. Clin Exp Immunol, 2023, 211: 208-223. doi:  10.1093/cei/uxac107
    [16] Gergely PJ, Grossman C, Niland B, et al. Mitochondrial hyperpolarization and ATP depletion in patients with systemic lupus erythematosus[J]. Arthritis Rheum, 2002, 46: 175-190. doi:  10.1002/1529-0131(200201)46:1<175::AID-ART10015>3.0.CO;2-H
    [17] Wahl DR, Petersen B, Warner R, et al. Characterization of the metabolic phenotype of chronically activated lymphocytes[J]. Lupus, 2010, 19: 1492-1501. doi:  10.1177/0961203310373109
    [18] Lee HT, Lin CS, Lee CS, et al. Increased 8-hydroxy-2'-deoxyguanosine in plasma and decreased mRNA expres-sion of human 8-oxoguanine DNA glycosylase 1, anti-oxidant enzymes, mitochondrial biogenesis-related proteins and glycolytic enzymes in leucocytes in patients with systemic lupus erythematosus[J]. Clin Exp Immunol, 2014, 176: 66-77. doi:  10.1111/cei.12256
    [19] Lee HT, Lin CS, Pan SC, et al. Alterations of oxygen consumption and extracellular acidification rates by glutamine in PBMCs of SLE patients[J]. Mitochondrion, 2019, 44: 65-74. doi:  10.1016/j.mito.2018.01.002
    [20] Lee HT, Wu TH, Lin CS, et al. Oxidative DNA and mitochondrial DNA change in patients with SLE[J]. Front Biosci, 2017, 22: 493-503. doi:  10.2741/4497
    [21] Warner LM, Adams LM, Sehgal SN. Rapamycin prolongs survival and arrests pathophysiologic changes in murine systemic lupus erythematosus[J]. Arthritis Rheum, 1994, 37: 289-297. doi:  10.1002/art.1780370219
    [22] Hajizadeh S, DeGroot J, TeKoppele JM, et al. Extracellular mitochondrial DNA and oxidatively damaged DNA in synovial fluid of patients with rheumatoid arthritis[J]. Arthritis Res Ther, 2003, 5: R234-R240. doi:  10.1186/ar787
    [23] Li Y, Shen Y, Jin K, et al. The DNA Repair Nuclease MRE11A Functions as a Mitochondrial Protector and Prevents T Cell Pyroptosis and Tissue Inflammation[J]. Cell Metab, 2019, 30: 477-492. e476. doi:  10.1016/j.cmet.2019.06.016
    [24] Yang Z, Fujii H, Mohan SV, et al. Phosphofructokinase deficiency impairs ATP generation, autophagy, and redox balance in rheumatoid arthritis T cells[J]. J Exp Med, 2013, 210: 2119-2134. doi:  10.1084/jem.20130252
    [25] Li N, Li Y, Hu J, et al. A Link Between Mitochondrial Dysfunction and the Immune Microenvironment of Salivary Glands in Primary Sjögren's Syndrome[J]. Front Immunol, 2022, 13: 845209. doi:  10.3389/fimmu.2022.845209
    [26] Mankowski RT, Wohlgemuth SE, Bresciani G, et al. Intraoperative Hemi-Diaphragm Electrical Stimulation Demons-trates Attenuated Mitochondrial Function without Change in Oxidative Stress in Cardiothoracic Surgery Patients[J]. Antioxidants (Basel), 2023, 12: 1009. doi:  10.3390/antiox12051009
    [27] Yennemadi AS, Keane J, Leisching G. Mitochondrial bioenergetic changes in systemic lupus erythematosus immune cell subsets: Contributions to pathogenesis and clinical applications[J]. Lupus, 2023, 32: 603-611. doi:  10.1177/09612033231164635
    [28] Nanto HF, Yamazaki M, Murakami H, et al. Chronic heat stress induces renal fibrosis and mitochondrial dysfunction in laying hens[J]. J Anim Sci Biotechnol, 2023, 14: 81. doi:  10.1186/s40104-023-00878-5
    [29] Zhang S, Lv Y, Luo X, et al. Homocysteine promotes atherosclerosis through macrophage pyroptosis via endoplasmic reticulum stress and calcium disorder[J]. Mol Med, 2023, 29: 73.
    [30] Ren X, Zhou H, Sun Y, et al. MIRO-1 interacts with VDAC-1 to regulate mitochondrial membrane potent ial in Caenorhabditis elegans[J]. EMBO Rep, 2023, 24: e56297. doi:  10.15252/embr.202256297
    [31] Clifton LA, Wacklin KHP, Ådén J, et al. Creation of distinctive Bax-lipid complexes at mitochondrial membrane surfaces drives pore formation to initiate apoptosis[J]. Sci adv, 2023, 9: eadg7940. doi:  10.1126/sciadv.adg7940
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(3)  / Tables(3)

    Article Metrics

    Article views (1249) PDF downloads(49) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return