Poster Presentation Abstracts
Anti-interferon-alpha autoantibodies in patients with inborn errors of Immunity and rheumatic diseases before and during the COVID-19 pandemic

https://doi.org/10.1016/j.clim.2023.109568Get rights and content

Abstract

Introduction

Type 1 interferon (IFN) autoantibodies, such as anti-IFNα, have pathogenic significance in life-threatening COVID-19 pneumonia. Ten to twenty percent of severe COVID cases are associated with type I IFN autoantibodies. These autoantibodies likely pre-exist while others arise de novo relative to SARS-CoV-2 infection. It is unclear to what extent type I anti-IFN autoantibodies are induced by SARS-CoV-2 infection and contribute to COVID-19 severity. We investigated these phenomena in those with inborn errors of immunity (IEI) and rheumatic disease (RHE).

Aims

We aim to compare the prevalence and neutralization ability of anti-IFNα autoantibodies in IEI and RHE patients using archived blood samples before and after the COVID-19 pandemic began.

Methods

We determined the presence of autoantibodies against IFNα in plasma samples by enzyme linked immunosorbent assay in 453 patients with IEI or RHE who were testing either before or after the COVID-19 pandemic began in March 2020. Using flow cytometry, we determined the function of IFNα autoantibodies in plasma to block CD4T cell activation by inhibiting STAT-1 phosphorylation.

Results

We found that 25 patients with IEI or RHE were positive for anti-IFNα autoantibodies. 10 out of 229 patient samples collected before the pandemic (4.2%) tested positive whereas 15 out of 224 patient samples collected after the pandemic began (7.0%) were positive. Seven of the 25 patients (28%) who tested positive had neutralizing antibodies in plasma, which prevented STAT-1 phosphorylation in CD4T cells; all of these patients had partial recombination activating gene deficiency (pRD) except for one patient with autoimmunity, leukemia and selective IgA deficiency. One pRD patient had anti-IFNα autoantibodies with neutralization capacity before the pandemic, which persisted after hematopoietic stem cell transplantation (HSCT) with full immune reconstitution. The patient was immunized for SARS-CoV-2 before and after HSCT and acquired COVID-19 infection a year after HSCT. The patient was symptomatic but never hospitalized and fully recovered despite having anti-IFNα autoantibodies.

Conclusion

Anti-IFNα autoantibody levels were comparable before and after the start of the COVID-19 pandemic in IEI and RHE patients but only 28% of cases were neutralizing. The clinical implications of these autoantibodies are yet to be determined.

Keywords

Interferon alpha
Autoantibodies
COVID-19
Inborn errors of immunity
Rheumatic disease
Neutralizing antibodies

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