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

  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.