Autoantibodies to IL-1Ra and PGRN in severe COVID-19 are associated with inflammation-induced hyperphosphorylated antigen isoforms - PubMed
2 hours ago
- #Inflammation
- #Autoantibodies
- #COVID-19
- Severe COVID-Patients have been found to have autoantibodies against IL-1Ra and PGRN which leads to impaired inflammatory responses.
- The key findings include hyperphosphorylation of IL-1Ra at Thr111 and PGRN at Ser81 respectively in these patients.
- The autoantibodies contribute to reduced antigen levels as well as immune complex formation thereby enhancing IL-1 and TNF signaling.
- Phage-display technology was used to detect hyperphosphorylated isoforms in a national pandemic cohort showing that autoantibodies can be found in most patients.
- The level of autoantibodies is highest at baseline and declines over 12 months while hyperphosphorylated antigens decrease prior to the autoantibodies.
- Seropositivity associates with hyperinflammation and cytokine profiles suggesting a role in disease pathogenesis.
- Cytokine signaling can induce hyperphosphorylation of IL-1Ra and PGRN which is more pronounced in monocytes from seropositive patients than in healthy monocytes.