Data for: Cellular origin and characterization of autoantibodies against type I IFNs in COVID-19 and APS-1

Populations of the study includes eight patients with aIFN+ severe COVID-19. five aIFN- severe COVID-19 patients, five APS-1 patients, and ten healthy donors controls. The results of the analysis will refer to this specific group of individuals.

This study characterized type I IFN-reactive B cells in patients with severe COVID-19 with type I IFN-neutralizing autoantibodies (aIFN+) and patients with APS-1. Serum or plasma samples were screened for autoantibody reactivity, and type I IFN-reactive B cells were isolated by flow cytometry. Paired single-cell RNA sequencing (scRNA-seq) and B-cell receptor sequencing (scBCR-seq) were performed to characterize B-cell states, clonality, and differentiation trajectories. Selected antibodies were cloned and experimentally evaluated for IFN binding and neutralizing activity, with additional structural and affinity analyses performed on lead neutralizing antibodies.

The samples used for the deposited scRNA-seq dataset were collected in Sweden and Italy under the relevant ethical approvals Dnr 2020-01558, Pavia Ethics Committee approval P-20200029440, and Dnr 2023-02698-02. The Italian samples were collected within the ATAC consortium at Fondazione IRCCS Policlinico San Matteo (Pavia, Italy) and transferred to Karolinska Institutet under a Material Transfer Agreement between Fondazione IRCCS Policlinico San Matteo and Karolinska Institutet. The approved Italian protocol includes Karolinska Institutet as a collaborating partner and permits anonymized samples to be analyzed by consortium partners. scRNA-seq data were generated at Karolinska Institutet from samples originating from both Sweden and Italy. The deposited dataset contains no direct personal identifiers.