Autoantibodies against type I interferons correlate with low CD169/SIGLEC1 and severe non-viral infections in ER patients

Neutralizing autoantibodies against type I interferons are a risk factor for multiple severe viral diseases. The timely detection of these autoantibodies remains an unmet need. We hypothesized that paradoxically low expression of type I IFN-induced CD169/SIGLEC1 expression analyzed by flow cytometry may allow rapid screening for the presence of these autoantibodies. In a prospective cohort study, we quantified monocytic CD169/SIGLEC1 expression and neutralizing autoantibodies against type I interferons in 808 patients who presented to the emergency room with signs of acute infections during the second wave of the SARS-CoV-2 pandemic in Germany in 2021. In patients, elevated CD169/SIGLEC1 (>2400 mAb/cell) demonstrated a negative predictive value of 100% for the detection of neutralizing autoantibodies against type I interferons. Low CD169/SIGLEC1 (<2400 mAb/cell) and a CRP >50 mg/L exhibited a positive predictive value of 70% for neutralizing autoantibodies against type I interferons. We further compared the adjusted odds ratio for mortality in patients with these autoantibodies to that in patients without autoantibodies against type I interferons. Neutralizing autoantibodies against type I interferons were associated with a worse clinical outcome, independent of SARS-CoV-2 infection, implying their presence is a risk factor for a worse general outcome.