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.
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