The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection is associated with increased levels of autoantibodies targeting immunological proteins such as cytokines and chemokines. ...Reports further indicate that COVID‐19 patients may develop a broad spectrum of autoimmune diseases due to reasons not fully understood. Even so, the landscape of autoantibodies induced by SARS‐CoV‐2 infection remains uncharted territory. To gain more insight, we carried out a comprehensive assessment of autoantibodies known to be linked to diverse autoimmune diseases observed in COVID‐19 patients in a cohort of 231 individuals, of which 161 were COVID‐19 patients (72 with mild, 61 moderate, and 28 with severe disease) and 70 were healthy controls. Dysregulated IgG and IgA autoantibody signatures, characterized mainly by elevated concentrations, occurred predominantly in patients with moderate or severe COVID‐19 infection. Autoantibody levels often accompanied anti‐SARS‐CoV‐2 antibody concentrations while stratifying COVID‐19 severity as indicated by random forest and principal component analyses. Furthermore, while young versus elderly COVID‐19 patients showed only slight differences in autoantibody levels, elderly patients with severe disease presented higher IgG autoantibody concentrations than young individuals with severe COVID‐19. This work maps the intersection of COVID‐19 and autoimmunity by demonstrating the dysregulation of multiple autoantibodies triggered during SARS‐CoV‐2 infection. Thus, this cross‐sectional study suggests that SARS‐CoV‐2 infection induces autoantibody signatures associated with COVID‐19 severity and several autoantibodies that can be used as biomarkers of COVID‐19 severity, indicating autoantibodies as potential therapeutical targets for these patients.
Ameloblasts are specialized epithelial cells in the jaw that have an indispensable role in tooth enamel formation-amelogenesis
. Amelogenesis depends on multiple ameloblast-derived proteins that ...function as a scaffold for hydroxyapatite crystals. The loss of function of ameloblast-derived proteins results in a group of rare congenital disorders called amelogenesis imperfecta
. Defects in enamel formation are also found in patients with autoimmune polyglandular syndrome type-1 (APS-1), caused by AIRE deficiency
, and in patients diagnosed with coeliac disease
. However, the underlying mechanisms remain unclear. Here we show that the vast majority of patients with APS-1 and coeliac disease develop autoantibodies (mostly of the IgA isotype) against ameloblast-specific proteins, the expression of which is induced by AIRE in the thymus. This in turn results in a breakdown of central tolerance, and subsequent generation of corresponding autoantibodies that interfere with enamel formation. However, in coeliac disease, the generation of such autoantibodies seems to be driven by a breakdown of peripheral tolerance to intestinal antigens that are also expressed in enamel tissue. Both conditions are examples of a previously unidentified type of IgA-dependent autoimmune disorder that we collectively name autoimmune amelogenesis imperfecta.
