| Title: |
Inactive disease in patients with lupus is linked to autoantibodies to type I interferons that normalize blood IFNα and B cell subsets. |
| Authors: |
Bradford, HF; Haljasmägi, L; Menon, M; McDonnell, TCR; Särekannu, K; Vanker, M; Peterson, P; Wincup, Chris; Abida, R; Gonzalez, RF; Bondet, V; Duffy, D; Isenberg, DA; Kisand, K; Mauri, C |
| Source: |
Bradford, HF, Haljasmägi, L, Menon, M, McDonnell, TCR, Särekannu, K, Vanker, M, Peterson, P, Wincup, C, Abida, R, Gonzalez, RF, Bondet, V, Duffy, D, Isenberg, DA, Kisand, K & Mauri, C 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, vol. 4, no. 1, 100894. https://doi.org/10.1016/j.xcrm.2022.100894 |
| Publication Year: |
2023 |
| Collection: |
The University of Manchester: Research Explorer - Publications |
| Subject Terms: |
B cells; SLE; autoimmunity |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/36652906 |
| DOI: |
10.1016/j.xcrm.2022.100894 |
| Availability: |
https://research.manchester.ac.uk/en/publications/48fd12d7-481c-434e-80ae-31b84f485013; https://doi.org/10.1016/j.xcrm.2022.100894; https://europepmc.org/articles/PMC9873953; https://www.scopus.com/pages/publications/85146268108; https://www.mendeley.com/catalogue/6d300220-4f38-3a39-917c-2083a799bd5f/ |
| Rights: |
info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.9A429D4D |
| Database: |
BASE |