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Wilhelm M, Bonam SR, Schall N, et al. Implication of a lysosomal antigen in the pathogenesis of lupus erythematosus. J Autoimmun. 2021;120:102633doi: 10.1016/j.jaut.2021.102633.
Wilhelm, M., Bonam, S. R., Schall, N., Bendorius, M., Korganow, A. S., Lumbroso, C., & Muller, S. (2021). Implication of a lysosomal antigen in the pathogenesis of lupus erythematosus. Journal of autoimmunity, 120102633. https://doi.org/10.1016/j.jaut.2021.102633
Wilhelm, Maud, et al. "Implication of a lysosomal antigen in the pathogenesis of lupus erythematosus." Journal of autoimmunity vol. 120 (2021): 102633. doi: https://doi.org/10.1016/j.jaut.2021.102633
Wilhelm M, Bonam SR, Schall N, Bendorius M, Korganow AS, Lumbroso C, Muller S. Implication of a lysosomal antigen in the pathogenesis of lupus erythematosus. J Autoimmun. 2021 Jun;120:102633. doi: 10.1016/j.jaut.2021.102633. Epub 2021 Apr 28. PMID: 33932829.
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J Autoimmun. 2021 Jun;120:102633. doi: 10.1016/j.jaut.2021.102633. Epub 2021 Apr 28.

Implication of a lysosomal antigen in the pathogenesis of lupus erythematosus.

Journal of autoimmunity

Maud Wilhelm, Srinivasa Reddy Bonam, Nicolas Schall, Mykolas Bendorius, Anne-Sophie Korganow, Catherine Lumbroso, Sylviane Muller

Affiliations

  1. CNRS, Strasbourg University Unit Biotechnology and Cell Signaling / Strasbourg Drug Discovery and Development Institute (IMS); Ecole Supérieure de Biotechnologie de Strasbourg, Illkirch, France.
  2. Department of Clinical Immunology and Internal Medicine, National Reference Center for Systemic Autoimmune Diseases (CNR RESO), Hôpitaux Universitaires de Strasbourg, France; Strasbourg University, INSERM Unit Molecular ImmunoRheumatology, Strasbourg, France; Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg University, Strasbourg, France.
  3. Centre Hospitalier Taaone, Papeete, French Polynesia.
  4. CNRS, Strasbourg University Unit Biotechnology and Cell Signaling / Strasbourg Drug Discovery and Development Institute (IMS); Ecole Supérieure de Biotechnologie de Strasbourg, Illkirch, France; Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg University, Strasbourg, France; University of Strasbourg Institute for Advanced Study, Strasbourg, France. Electronic address: [email protected].

PMID: 33932829 DOI: 10.1016/j.jaut.2021.102633

Abstract

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.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Keywords: Autoantibodies; Autophagy; LAMP2A; Lupus; Lysosomes

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