Broad responses to chemical adducts shape the natural antibody repertoire in early infancy.

Natural antibodies are an integral part of innate humoral immunity yet their development and polyreactive nature are still enigmatic. Here, we show that characteristic monoclonal natural antibodies recognize common chemical moieties or adducts, supporting the view that polyreactive antibodies may often correspond to anti-adduct antibodies. We next examined the development of immunoglobulin M (IgM) and IgG to 81 ubiquitous adducts from birth to old age.

Epicutaneous immunotherapy protects cashew-sensitized mice from anaphylaxis.

Background: The prevalence of tree nut allergy has increased worldwide, and cashew has become one of the most common food allergens. More critically, cashew allergy is frequently associated with severe anaphylaxis. Despite the high medical need, no approved treatment is available and strict avoidance and preparedness for prompt treatment of allergic reactions are considered dual standard of care.

Type I interferon-mediated autoinflammation due to DNase II deficiency.

Microbial nucleic acid recognition serves as the major stimulus to an antiviral response, implying a requirement to limit the misrepresentation of self nucleic acids as non-self and the induction of autoinflammation. By systematic screening using a panel of interferon-stimulated genes we identify two siblings and a singleton variably demonstrating severe neonatal anemia, membranoproliferative glomerulonephritis, liver fibrosis, deforming arthropathy and increased anti-DNA antibodies. In both families we identify biallelic mutations in DNASE2, associated with a loss of DNase II endonuclease activity.