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. 2023 Mar 31:6:100199.
doi: 10.1016/j.jtauto.2023.100199. eCollection 2023.

Immunological and translational key challenges in systemic lupus erythematosus: A symposium update

Yves Renaudineau  1   2 , Sylviane Muller  3 , Christian M Hedrich  4 , Dominique Chauveau  5 , Julie Bellière  5 , Sébastien De Almeida  6 , Jan Damoiseaux  7 , Marc Scherlinger  8 , Jean Charles Guery  2 , Laurent Sailler  6 , Chloé Bost  1   2
Affiliations

Immunological and translational key challenges in systemic lupus erythematosus: A symposium update

Yves Renaudineau et al. J Transl Autoimmun. .

Abstract

The first LBMR-Tim (Toulouse Referral Medical Laboratory of Immunology) symposium convened on December 16, 2022 in Toulouse, France to address challenging questions in systemic lupus erythematosus (SLE). Special focus was put on (i) the role played by genes, sex, TLR7, and platelets on SLE pathophysiology; (ii) autoantibodies, urinary proteins, and thrombocytopenia contribution at the time of diagnosis and during follow-up; (iii) neuropsychiatric involvement, vaccine response in the COVID-19 era, and lupus nephritis management at the clinical frontline; and (iv) therapeutic perspectives in patients with lupus nephritis and the unexpected adventure of the Lupuzor/P140 peptide. The multidisciplinary panel of experts further supports the concept that a global approach including basic sciences, translational research, clinical expertise, and therapeutic development have to be prioritized in order to better understand and then improve the management of this complex syndrome.

Keywords: COVID-19; Genetics; Lupus nephritis; Lupuzor; Nervous system; Platelets; Systemic lupus erythematosus; TLR7; Vaccine.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Systemic lupus erythematosus (SLE) pathophysiology and implications for treatments. SLE pathophysiology comprises three parts. First, a cellular debris accumulation with cell surface exposed autoantigens. This step is promoted by the cellular apoptosis and cellular activation including from platelets, by genetic factors, and by autoantibodies to form immune complexes. Second, antigen presenting cells are hyperactivated and produce high levels of interferon (IFN)-alpha, which resulted from genetic and immune gene dysregulation involving Toll like receptor (TLR)7 on the X chromosome. The HSPA8/HSC70 chaperone autophagy pathway leading to an exacerbated autoantigen presentation is also abnormally hyperactivated. Third, an extrafollicular immune response takes place characterized by inflammation, a defective T cell and B cell response. Abbreviations: UV ultraviolet light; DNA: deoxyribonucleic acid RNA: ribonucleic acid; autoAb: autoantibody; Ab antibody; HCQ: hydroxychloroquine, MHC II: major histocompatibility/human leukocyte antigen type II; Pts: platelets; IFN-α: interferon type I; BAFF: B cell activating factor; Treg: regulatory T cells; Tmem: memory T cell; TFH: follicular helper T cell; XCI: X chromosome inactivation; TREX: three prime repair exonuclease 1; MDA5: melanoma differentiation-associated protein 5; STING: stimulator of interferon genes; TLR7/9: toll like receptor 7/9. This figure was made with Servier Medical Art templates (https://smart.servier.com).
Fig. 2
Fig. 2
Lupus nephritis improvement remains modest in the last two decades regarding therapies, pathology and biomarkers.
See this image and copyright information in PMC

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