Autoantibodies are highly prevalent in non–SARS-CoV-2 respiratory infections and critical illness
Allan Feng, et al.
Allan Feng, et al.
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Research Article Infectious disease

Autoantibodies are highly prevalent in non–SARS-CoV-2 respiratory infections and critical illness

Abstract

The widespread presence of autoantibodies in acute infection with SARS-CoV-2 is increasingly recognized, but the prevalence of autoantibodies in non–SARS-CoV-2 infections and critical illness has not yet been reported. We profiled IgG autoantibodies in 267 patients from 5 independent cohorts with non–SARS-CoV-2 viral, bacterial, and noninfectious critical illness. Serum samples were screened using Luminex arrays that included 58 cytokines and 55 autoantigens, many of which are associated with connective tissue diseases (CTDs). Samples positive for anti-cytokine antibodies were tested for receptor blocking activity using cell-based functional assays. Anti-cytokine antibodies were identified in > 50% of patients across all 5 acutely ill cohorts. In critically ill patients, anti-cytokine antibodies were far more common in infected versus uninfected patients. In cell-based functional assays, 11 of 39 samples positive for select anti-cytokine antibodies displayed receptor blocking activity against surface receptors for Type I IFN, GM-CSF, and IL-6. Autoantibodies against CTD-associated autoantigens were also commonly observed, including newly detected antibodies that emerged in longitudinal samples. These findings demonstrate that anti-cytokine and autoantibodies are common across different viral and nonviral infections and range in severity of illness.

Authors

Allan Feng, Emily Y. Yang, Andrew Reese Moore, Shaurya Dhingra, Sarah Esther Chang, Xihui Yin, Ruoxi Pi, Elisabeth K.M. Mack, Sara Völkel, Reinhard Geßner, Margrit Gündisch, Andreas Neubauer, Harald Renz, Sotirios Tsiodras, Paraskevi C. Fragkou, Adijat A. Asuni, Joseph E. Levitt, Jennifer G. Wilson, Michelle Leong, Jennifer H. Lumb, Rong Mao, Kassandra Pinedo, Jonasel Roque, Christopher M. Richards, Mikayla Stabile, Gayathri Swaminathan, Maria L. Salagianni, Vasiliki Triantafyllia, Wilhelm Bertrams, Catherine A. Blish, Jan E. Carette, Jennifer Frankovich, Eric Meffre, Kari Christine Nadeau, Upinder Singh, Taia T. Wang, Eline T. Luning Prak, Susanne Herold, Evangelos Andreakos, Bernd Schmeck, Chrysanthi Skevaki, Angela J. Rogers, Paul J. Utz

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Figure 2

IgG anti-cytokine autoantibodies in serum from patients with ARDS or patients acutely infected with influenza virus.

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IgG anti-cytokine autoantibodies in serum from patients with ARDS or pat...
Tukey box plots comparing MFI data for 8 cytokines in patients with influenza (n = 25) and patients with ARDS (n = 17), both collected prior to the COVID-19 pandemic; patients with ARDS who were COVID-19– (n = 19); and HC (n = 11). One COVID-19 PCR-negative patient from the Marburg cohort had high levels of antibodies targeting SARS-CoV-2 proteins from our viral array and was excluded from this figure and other analyses (Supplemental Figure 6). The middle line represents the median, while the lower and upper hinges correspond to the first and third quartiles. The upper whisker extends from the hinge to 1.5 times the IQR above the 75th percentile MFI value, and the lower whisker extends from the hinge to 1.5 times the IQR below the 25th percentile MFI value. Black arrows indicate a serum sample with receptor-blocking activity (see Figure 4). Individual MFI values 1.5 times the IQR above the 75th percentile or 1.5 times the IQR below the 25th percentile are displayed as dots. MFI is shown on the y axis, which is hatched to reflect outlier samples with very high MFI. Cohorts are shown on the x axis.