SP0174 ADVANCES IN THE DETECTION OF PATHOGENIC AUTOANTIBODIES IN SLE

Abstract

Background: The accumulation of late apoptotic or so-called Secondary NEcrotic Cells (SNEC) in germinal centers challenges B and T cell tolerance and leads to the development of autoimmunity and the production of autoantibodies. Objectives: Determine the test performance of immobilized SNEC autoantigens for the diagnosis of Systemic Lupus Erythematosus. Methods: SNEC ELISA of sera from patients with SLE and test performance statistics were deployed to evaluate the diagnostic potential SNEC-derived autoantigens. Functional assays confirmed its pathophysiological relevance. Results: SNEC contains nuclear autoantigens bearing apoptosis-associated modifications such as histone H3 K27me3, histone H2A/H4AcK8,12,16, and histone H2B-AcK12. The SNEC ELISA clearly discriminated patients with SLE from patients with Rheumatoid Arthritis (RA), Primary Anti-Phospholipid Syndrome (PAPS), Spondyloarthropathy (SpA), Psoriatic Arthritis (PsA), and Systemic Sclerosis (SSc). A positive test result in SNEC ELISA significantly correlated with serological variables and reflected the uptake of opsonized SNEC by neutrophils in the blood. Conclusion: SNEC ELISA allows for the sensitive detection of pathologically relevant autoantibodies in the serum of patients with SLE. The clearance of nuclear remnants by neutrophils enhances inflammatory responses supporting the role of clearance deficiency in the etiopathogenesis of SLE. Reference: [1] Biermann MHC, Boeltz S, Pieterse E, Knopf J, Rech J, Bilyy R, van der Vlag J, Tincani A, Distler JHW, Kronke G, Schett GA, Herrmann M and Munoz LE (2018) Autoantibodies Recognizing Secondary NEcrotic Cells Promote Neutrophilic Phagocytosis and Identify Patients With Systemic Lupus Erythematosus. Front. Immunol. 9:989. doi: 10.3389/fimmu.2018.00989 Disclosure of Interests: None declared