Background/Purpose: Primary Sjögren’s Syndrome (pSS) is a systemic autoimmune disorder characterized by lymphocytic infiltrations in exocrine glands. T-cells are considered major players in the pathogenesis of pSS. Previously, we reported naïve CD4+ T-cells exhibited signs of immune cell aging including shortened telomeres, increased senescence-associated -β-galactosidase activity, a reduction in IL-7R expression and reduced level of T-cell receptor excision circles. Homeostatic proliferation of naïve CD4+ T-cells was impared both ex vivo and after stimulation in vitro. Senescencence and impaired homeostasis of pSS naïve CD4+ T-cells lead to peripheral lymphopenia, a frequent finding in pSS patients. As mitochondrial fitness has been linked to cellular aging and AI conditions, we assessed mitochondrial parameters in T cells of pSS patients.

Methods: Peripheral blood mononuclear cells (PBMC) were isolated from venous blood of pSS patients fulfilling 2016 ACR/EULAR classification criteria and sex- and age-matched healthy control subjects (HC). Flow cytometric analysis was performed to identify and further characterise CD4+ T-cell subsets (Naïve, Central memory, Effector memory and Terminally differentiated effector memory) at single-cell level: staining with mitochondrion‐selective fluorescent dyes MitoTracker® Green (MTG), MitoTracker® Deep Red (MTDR), MitoSox Red was performed to assess mitochondrial mass, membrane potential (MtMP) and superoxide production, respectively. Mitochondrial fitness was assessed by combined staining method with MTG and MTDR.Uptake of glucose analogue 2-NBDG was used to monitor glucose uptake ability of the CD4+ T-cell subsets.

Results: Staining with MTG and MTDR showed decreased mitochondrial mass and mitochondrial membrane potential in all CD4+ T-cell subsets of pSS patients. Despite having reduced mitochondrial mass and MtMP, we observed that pSS T-cells produced higher amount of mitochondrial superoxides compared to HC. Percentage of dysfunctional mitochondria (MTG high, MTDR low) was significantly increased in pSS, probably due to accumulation of mitochondrial superoxides. On the other hand, glucose uptake was increased in all pSS CD4+ T-cells, which can indicate enhanced glycolysis.

Conclusion: We found that T-cells premature aging in pSS patients is linked with mitochondrial dysfunction associated with accumulation of mitochondrial superoxides and enhanced glucose uptake ex vivo. The underlying mechanisms of mitochondrial dysfunction of T-cells in primary Sjögren’s Syndrome should be investigated in further studies.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/mitochondrial-alterations-in-primary-sjogrens-syndrome/