Implication of a lysosomal antigen in the pathogenesis of lupus erythematosus
Autor: | Maud Wilhelm, Srinivasa Reddy Bonam, Catherine Lumbroso, Nicolas Schall, Mykolas Bendorius, Sylviane Muller, Anne-Sophie Korganow |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Mice Inbred MRL lpr Immunology Autoimmunity Enzyme-Linked Immunosorbent Assay Endosomes Autoantigens Pathogenesis Mice 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Antigen immune system diseases Lysosomal-Associated Membrane Protein 2 Autophagy medicine Animals Humans Lupus Erythematosus Systemic Immunology and Allergy Antigens skin and connective tissue diseases Heat-Shock Proteins Autoantibodies 030203 arthritis & rheumatology Systemic lupus erythematosus Lupus erythematosus biology Autoantibody medicine.disease Disease Models Animal Membrane glycoproteins 030104 developmental biology Case-Control Studies Immunoglobulin G biology.protein Disease Susceptibility Lysosomes Peptides Biomarkers |
Zdroj: | Journal of Autoimmunity. 120:102633 |
ISSN: | 0896-8411 |
Popis: | Naturally-occurring autoantibodies to certain components of autophagy processes have been described in a few autoimmune diseases, but their fine specificity, their relationships with clinical phenotypes, and their potential pathogenic functions remain elusive. Here, we explored IgG autoantibodies reacting with a panel of cytoplasmic endosomal/lysosomal antigens and individual heat-shock proteins, all of which share links to autophagy. Sera from autoimmune patients and from MRL/lpr and NZB/W lupus-prone mice reacted with the C-terminal residues of lysosome-associated membrane glycoprotein (LAMP)2A. No cross-reaction was observed with LAMP2B or LAMP2C variants, with dsDNA or mononucleosomes, or with heat-shock protein A8. Moreover, administering chromatography-purified LAMP2A autoantibodies to MRL/lpr mice accelerated mortality. Furthermore, flow cytometry revealed elevated cell-surface expression of LAMP2A on MRL/lpr B cells. These findings reveal the involvement of a new class of autoantibodies targeting the C-terminus of LAMP2A, a receptor for cytosolic proteins targeted for degradation via chaperone-mediated autophagy. These autoantibodies could affect the autophagy process, which is abnormally upregulated in lupus. The data presented support a novel connection between autophagy dysregulation, autoimmune processes and pathophysiology in lupus. |
Databáze: | OpenAIRE |
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