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. 2025 Jul;102(1):e70039.
doi: 10.1111/sji.70039.

Evaluating IL1RA-Autoantibodies Across SARS-CoV-2-Related Diseases

Affiliations

Evaluating IL1RA-Autoantibodies Across SARS-CoV-2-Related Diseases

Anish Behere et al. Scand J Immunol. 2025 Jul.
No abstract available

Keywords: COVID‐19; IL1RA; MIS‐C; adverse events following immunisation; autoantibodies; myocarditis.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Patients with multisystem inflammatory syndrome in children (MIS‐C, n = 28), COVID‐19 vaccine‐associated myocarditis and perimyocarditis (Cardiac AEFI, n = 47), severe COVID‐19 pneumonia (n = 48), COVID‐19 vaccine‐associated thrombosis (Non‐cardiac AEFI, n = 47) plasma samples and blood donor samples were tested for autoantibodies against IL1RA. (A) A heatmap showing the unique antigen‐specific reactivities with log2 fold‐change above the pre‐pandemic blood donor group (grey, n = 38), from a multiplex bead assay experiment. Elevated and shared immunoreactivity against multiple type‐I interferons was observed in the severe COVID‐19 pneumonia patient group. However, none of the disease groups showed elevated immunoreactivity against IL1RA (HEK293T cell‐expression system) (B) In the same experiment, IL1RA protein from three sources, as well as technical controls in the form of a representative type‐I interferon (IFNA16), SARS‐CoV‐2 Spike protein and Epstein–Barr virus Nuclear Antigen (EBNA1) were included. The red‐dotted threshold line indicates mean + 5 SD over MFI value of pre‐pandemic blood donor group, while blue‐dotted line indicates lower limit of detection of the bead assay. (C) IL1RA autoantibodies were measured using a sandwich ELISA with human IL1RA protein. The red‐dotted threshold line indicates mean + 7 SD over OD value at 450 nm of pre‐pandemic blood donors' group. (D) Samples were tested for IL1RA neutralisation using a cell‐based IL1 reporter assay. HEK‐Blue IL‐1β cells were stimulated with recombinant IL‐1β in the presence of IL1RA, with or without rabbit anti‐IL1RA antibody or samples. The resultant release of SEAP in proportion with IL1R‐mediated cell stimulation was measured at 650 nm using manufacturer reagents. The red‐dotted threshold line indicates IC50 threshold calculated based on IL‐1β sole stimulation versus IL‐1β + IL1RA co‐stimulation. IC50, half maximal inhibitory concentration; MFI, Mean Fluorescence Intensity; OD, optical density; SD, standard deviation; SEAP, Secreted Embryonic Alkaline Phosphatase.

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