Inactive disease in lupus patients is linked to autoantibodies to type-I interferons that normalize blood IFNα and B cell subsets - Institut Pasteur Access content directly
Journal Articles Cell Reports Medicine Year : 2023

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

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.

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Immunology
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Origin : Publication funded by an institution
Licence : CC BY - Attribution

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pasteur-03244412 , version 1 (08-02-2023)

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Madhvi Menon, Hannah Bradford, Liis Haljasmagi, Martti Vanker, Pärt Peterson, et al.. Inactive disease in lupus patients is linked to autoantibodies to type-I interferons that normalize blood IFNα and B cell subsets. Cell Reports Medicine, 2023, 4 (1), pp.100894. ⟨10.1101/2021.04.07.21255049⟩. ⟨pasteur-03244412⟩

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