Longitudinal single-cell epitope and RNA-sequencing reveals the immunological impact of type 1 interferon autoantibodies in critical COVID-19
van der Wijst, M. G. P.; Vazquez, S. E.; Hartoularos, G. C.; Bastard, P.; Grant, T.; Bueno, R.; Lee, D. S.; Greenland, J. R.; Sun, Y.; Perez, R.; Ogorodnikov, A.; Ward, A.; Mann, S. A.; Lynch, K. L.; Yun, C.; Havlir, D. V.; Chamie, G.; Marquez, C.; Greenhouse, B.; Lionakis, M. S.; Norris, P. J.; Dumont, L. J.; Kelly, K.; Zhang, P.; Zhang, Q.; Gervais, A.; Le Voyer, T.; Whatley, A.; Si, Y.; Byrne, A.; Combes, A. J.; Arkal, A.; Song, Y. S.; Fragiadakis, G. K.; UCSF COMET consortium, ; Kangelaris, K.; Calfee, C. S.; Erle, D. J.; Hendrickson, C.; Krummel, M. F.; Woodruff, P. G.; Langelier, C. R.;
Show abstract
Type I interferon (IFN-I) neutralizing autoantibodies have been found in some critical COVID-19 patients; however, their prevalence and longitudinal dynamics across the disease severity scale, and functional effects on circulating leukocytes remain unknown. Here, in 284 COVID-19 patients, we found IFN-I autoantibodies in 19% of critical, 6% of severe and none of the moderate cases. Longitudinal profiling of over 600,000 peripheral blood mononuclear cells using multiplexed single-cell epitope and transcriptome sequencing from 54 COVID-19 patients, 15 non-COVID-19 patients and 11 non-hospitalized healthy controls, revealed a lack of IFN-I stimulated gene (ISG-I) response in myeloid cells from critical cases, including those producing anti-IFN-I autoantibodies. Moreover, surface protein analysis showed an inverse correlation of the inhibitory receptor LAIR-1 with ISG-I expression response early in the disease course. This aberrant ISG-I response in critical patients with and without IFN-I autoantibodies, supports a unifying model for disease pathogenesis involving ISG-I suppression via convergent mechanisms.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- The COVID-19 immune landscape is dynamically and reversibly correlated with disease severity 97%
- Blood immunophenotyping identifies distinct kidney histopathology and outcomes in patients with lupus nephritis 96%
- CXCL8 secreted by immature granulocytes inhibits wildtype hematopoiesis in chronic myelomonocytic leukemia 95%
Similar papers in this journal
- ScRNA-Seq study of neutrophils reveals vast heterogeneity and breadth of inflammatory responses in severe COVID-19 patients 97%
- Dysregulated immune responses in COVID-19 patients correlating with disease severity and invasive oxygen requirements 97%
- Prognostic peripheral blood biomarkers at ICU admission predict COVID-19 clinical outcomes 96%
Similar papers in this journal
- Integrated single-cell transcriptomics and epigenomics reveals strong germinal center-associated etiology of autoimmune risk loci 96%
- ZEB2 regulates the development of CD11c+ atypical B cells 96%
- Loss-of-function mutation in IKZF2 leads to immunodeficiency with dysregulated germinal center reactions and reduction of MAIT cells. 96%
Similar papers in this journal
- A multimorphic variant in ThPOK causes a novel human disease characterized by T cell abnormalities, immunodysregulation, allergy, and fibrosis 96%
- Multi-omic profiling reveals widespread dysregulation of innate immunity and hematopoiesis in COVID-19 95%
- Plasmodium falciparum-specific IgM B cells dominate in children, expand with malaria and produce parasite inhibitory IgM 94%
Similar papers in this journal
- Neutrophil Profiles of Pediatric COVID-19 and Multisystem Inflammatory Syndrome in Children 97%
- Rewired type I IFN signaling is linked to age-dependent differences in COVID-19 96%
- Profiling Transcription Initiation in Peripheral Leukocytes Reveals Severity-Associated Cis-Regulatory Elements in Critical COVID-19 96%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.