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Inactive disease in patients with lupus is linked to autoantibodies to type I interferons that normalize blood IFNα and B cell subsets

Bradford, Hannah F; Haljasmägi, Liis; Menon, Madhvi; McDonnell, Thomas CR; Särekannu, Karita; Vanker, Martti; Peterson, Pärt; ... Mauri, Claudia; + view all (2023) Inactive disease in patients with lupus is linked to autoantibodies to type I interferons that normalize blood IFNα and B cell subsets. Cell Reports Medicine , 4 (1) , Article 100894. 10.1016/j.xcrm.2022.100894. Green open access

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Abstract

Systemic lupus erythematosus (SLE) is characterized by increased expression of type I interferon (IFN)-regulated genes in 50%-75% of patients. We report that out of 501 patients with SLE analyzed, 73 (14%) present autoantibodies against IFNα (anti-IFN-Abs). The presence of neutralizing-anti-IFN-Abs in 4.2% of patients inversely correlates with low circulating IFNα protein levels, inhibition of IFN-I downstream gene signatures, and inactive global disease score. Hallmarks of SLE pathogenesis, including increased immature, double-negative plasmablast B cell populations and reduction in regulatory B cell (Breg) frequencies, were normalized in patients with neutralizing anti-IFN-Abs compared with other patient groups. Immunoglobulin G (IgG) purified from sera of patients with SLE with neutralizing anti-IFN-Abs impedes CpGC-driven IFNα-dependent differentiation of B cells into immature B cells and plasmablasts, thus recapitulating the neutralizing effect of anti-IFN-Abs on B cell differentiation in vitro. Our findings highlight a role for neutralizing anti-IFN-Abs in controlling SLE pathogenesis and support the use of IFN-targeting therapies in patients with SLE lacking neutralizing-anti-IFN-Abs.

Type: Article
Title: Inactive disease in patients with lupus is linked to autoantibodies to type I interferons that normalize blood IFNα and B cell subsets
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.xcrm.2022.100894
Publisher version: https://doi.org/10.1016/j.xcrm.2022.100894
Language: English
Additional information: Crown Copyright © 2022. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: B cells, SLE, autoimmunity, Humans, Interferon Type I, Autoantibodies, B-Lymphocyte Subsets, Interferon-alpha, Lupus Erythematosus, Systemic
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10163853
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