Exploring cell-free mitochondria as a potential non-invasive biomarker of lupus nephritis

Abstract

Background: Systemic lupus erythematosus (SLE) is a systemic chronic autoimmune disease. Lupus nephritis (LN) is one of the major manifestations of SLE affecting up to ~60% SLE patients. According to European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR), a positive renal biopsy along with a positive antinuclear antibody (ANA) and/or anti-double-stranded DNA (anti-dsDNA) antibody is required for confirmation and classification of LN. Renal biopsy is the gold standard to diagnose and classify LN, but it is invasive and costly. Therefore, there is a need for less invasive, risk-free systemic biomarkers to predict disease activity and treatment outcomes. Cells under oxidative stress can release various Mitochondrial Danger Associated Molecular Patterns (DAMPs) including naked or vesicle-enclosed forms of mitochondria itself known as cell-free mitochondria (cf-mitochondria), mitochondrial DNA etc. Stressful conditions are also well known to cause mitochondrial extrusion by damaged organs. The cf-mitochondria can act as auto-antigen, thus triggering immune response leading to production of anti-mitochondrial DNA autoantibodies.