Mitochondrial mass and mitochondrial membrane potential of peripheral lymphocytes: promising biomarkers of systemic lupus erythematosus

Guanfei Zhao¹Haolong Li^2*Yutong Miao¹Linlin Cheng²Yuying Chen¹Yuan Huang²Hongyun Zhao¹Yongmei Liu²Yongzhe Li²Rui Zhang¹

• ¹Department of Clinical Laboratory, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
• ²Department of Clinical Laboratory, Peking Union Medical College Hospital, Beijing, China

Background: Mitochondrial dysfunction is implicated in the pathogenesis of systemic lupus erythematosus (SLE). Single-cell mitochondrial mass (SCMM) and low mitochondrial membrane potential (MMP-Low) in lymphocytes, as well as circulating mitochondrial DNA (mtDNA), can reflect the mitochondrial impairment and have the potential role as novel biomarkers for SLE.Purpose: We investigated the diagnostic utility of MMP-Low and SCMM in lymphocytes, as well as circulating mtDNA levels, in patients with SLE and examined their correlation with disease activity.Methods: Flow cytometry was performed to detect MMP-Low and SCMM in peripheral lymphocytes from patients with SLE (n = 52) and healthy controls (n =30). The level of circulating mtDNA was quantified by PCR. Results: Patients with SLE exhibited a significantly decreased MMP-Low in some peripheral lymphocyte subsets. Meanwhile, a significantly increased SCMM in some lymphocyte subsets and circulating mtDNA were observed in patients with SLE. CD8+ T naïve cell (Tn) MMP-Low, CD8+ T effector memory cell MMP-Low, CD8+ T central memory cell (Tcm) MMP-Low, and SCMM-CD8+ Tn demonstrated a moderate diagnostic value for SLE, with an area under the curve above 0.8. Both CD4+ Tcm MMP-Low and SCMM-CD3+CD4+ T cells were significantly associated with the SLE Disease Activity Index 2000 and circulating mtDNA levels. Both CD4+ Tcm MMP-Low and SCMM-CD3+CD4+ T cells showed significantly alternations between inactive and active SLE.Conclusions: Our data showed that patients with SLE had mitochondrial dysfunction. Several MMP-Low and SCMM in CD8+T cell subsets could serve as potential biomarkers for diagnosing SLE. Additionally, CD4+ Tcm MMP-Low and SCMM-CD3+CD4+ T cells were associated with SLE disease activity.