Autoantibodies against Type I Interferons Correlate with Low CD169/SIGLEC1 and Severe Non-Viral Infections in ER Patients.

Autoantibodies against Type I Interferons Correlate with Low CD169/SIGLEC1 and Severe Non-Viral Infections in ER Patients.

Publication date: Dec 02, 2025

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 (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 the one 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.

Concepts Keywords
Germany CD169
Immunol SARS-CoV-2
Mortality SIGLEC1

Semantics

Type Source Name
disease MESH Viral Infections
disease MESH emergency
disease MESH infections
disease IDO cell
disease MESH SARS-CoV-2 infection
pathway REACTOME SARS-CoV-2 Infection

Original Article

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