Sjögren's Disease and Mitochondrial Function

Biji T Kurien¹, Pharaoh Gavin², Joshua Cavett¹, Valerie Lewis³, Ambre Chambers¹, Bhaskaran Shylesh⁴, Anjum Juvaria¹, Brittany Karfonta¹, Lida Radfar¹, Astrid Rasmussen⁴, Christopher Lessard⁴, Darise Farris⁴, Kathy Sivils⁵, Kristi A Koelsch⁴, Holly Van Remmen⁴ and R. Hal Scofield¹, ¹University of Oklahoma Health Sciences Center, Oklahoma City, OK, ²University of Washington, Seattle, WA, ³Veterans Affairs Medical Center, Oklahoma City, OK, ⁴Oklahoma Medical Research Foundation, Oklahoma City, OK, ⁵Janssen Research and Development, LLC, Spring House, PA

Meeting: ACR Convergence 2022

Keywords: Fatigue, metabolic syndrome, Mitochondrial Dysfunction, Sjögren's syndrome, T Cell

Session Information

Date: Monday, November 14, 2022

Title: Sjögren's Syndrome – Basic and Clinical Science Poster

Session Type: Poster Session D

Session Time: 1:00PM-3:00PM

Background/Purpose: Sjögren’s disease (SjD) is a chronic inflammatory, autoimmune disorder with reduced lacrimal/salivary gland secretion resulting in keratoconjunctivitis sicca and xerostomia, respectively. Also, SjD patients have increased rates of metabolic syndrome and experience significant fatigue. Metabolic syndrome and fatigue are associated with chronic low-level inflammation. Our previous studies showed oxidative damage in systemic lupus erythematosus and oxidative modification of proteins in SjD. Oxidative damage, mitochondrial dysfunction, and metabolic syndrome have been studied only sporadically in SjD, and their associations have not been studied. We hypothesized that SjD subjects have mitochondrial dysfunction and that fatigue and oxidative damage will be present in a subset of subjects with SjD.

Methods: We enrolled 17 SjD subjects and seven age and sex-matched subjects at the Oklahoma Shared Clinical and Translational Resources in this study. Subjects underwent a fasting blood draw, lipid and glucose testing, BMI measurement, and completed a fatigue questionnaire. After isolating PBMCs from the blood, B cells were purified through positive selection, and T cells through negative selection using Miltenyi Biotech B and T cell isolation kit. We plated one million T cells/well on Cell Tak coated plate to make the cells adherent. The cells were analyzed for mitochondrial oxygen consumption rate (OCR) and extracellular acidification rate (glycolysis) using the Seahorse XF24 assay. SDS-PAGE analysis of plasma proteins followed by immunoblotting of 4-hydroxynonenal (HNE) modified proteins using anti-HNE antibody were also performed.

Results: Our previous studies confirmed oxidative damage in SjD, demonstrated by an HNE-modified plasma protein migrating at ~16 kD. In the present study, we did not find significant differences in non-mitochondrial respiration between controls and SjD [17.67±2.77 Standard Error (SE) Vs. 17.95±3.1 SE pmol/min/million cells]. However, basal OCR was significantly higher (p< 0.0001) in controls compared to SjD (114.94±16.13 SE Vs. 70±5.69 SE pmol/min/million cells). ATP-linked respiration was also significantly higher (p< 0.001) in controls than in SjD (116.07±16.79 SE Vs. 66.93±4.71 SE pmol/min/million cells). The biggest differences were in the maximal respiration (p< 0.0005) (controls- 421.3±88.35 SE; SjD- 173.97±17.21 SE pmol/min/million cells) and reserve capacity (p< 0.0002) (controls- 310.93±74.37 SE; SjD- 105.01±12.34 SE pmol/min/million cells). There was no significant difference in basal glycolysis or glycolytic stressed levels in controls and SjD. Our next steps will be to determine which of these SjD subjects have metabolic syndrome and oxidative damage and whether mitochondrial dysfunction, metabolic syndrome and oxidative damage occur in a sub-set of these SjD subjects.

Conclusion: Mitochondrial dysfunction appears to be a significant problem in SjD. We will analyze if it is associated with the metabolic syndrome and fatigue that frequently accompany SjD.

Disclosures: B. Kurien, None; P. Gavin, None; J. Cavett, None; V. Lewis, None; A. Chambers, None; B. Shylesh, None; A. Juvaria, None; B. Karfonta, None; L. Radfar, None; A. Rasmussen, None; C. Lessard, None; D. Farris, None; K. Sivils, Janssen Research & Development, LLC; K. Koelsch, None; H. Van Remmen, None; R. Scofield, None.

To cite this abstract in AMA style:

Kurien B, Gavin P, Cavett J, Lewis V, Chambers A, Shylesh B, Juvaria A, Karfonta B, Radfar L, Rasmussen A, Lessard C, Farris D, Sivils K, Koelsch K, Van Remmen H, Scofield R. Sjögren’s Disease and Mitochondrial Function [abstract]. Arthritis Rheumatol. 2022; 74 (suppl 9). https://acrabstracts.org/abstract/sjogrens-disease-and-mitochondrial-function/. Accessed .

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