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In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. However, their thymuses have an abnormal structure, with few AIRE-expressing medullary thymic epithelial cells. These autoantibodies were widely thought to be clinically silent, with the notable exception of a year-old woman who had such antibodies and disseminated shingles, reported in 5 , 6. These autoantibodies were also found to underlie severe adverse reactions to yellow fever live-attenuated viral vaccine 12 , influenza pneumonia 13 , MERS pneumonia 14 and West Nile virus encephalitis Finally, these autoantibodies are also present in the general population, with the prevalence sharply increasing in individuals over 70 years of age, thereby contributing to the age-related increase in the risk of severe COVID 7 , AIRE deficiency impairs the expression of tissue-specific antigens in medullary thymic epithelial cells mTECs , enabling autoreactive T cells to escape 18 , Patients with APS-1 display severe multiorgan autoimmunity with a wide range of autoantibodies against tissue-specific antigens This leads to p processing to generate the p52 amino acids 1— active form, which preferentially dimerizes with RELB This p52—RELB heterodimer migrates to the nucleus, inducing the transcription of target genes involved in lymphoid organ development, germinal centre formation, B cell survival, maturation, homeostasis, mTEC development and osteoclastogenesis Most affected individuals had a predominant phenotype of primary antibody deficiency PAD 62 out of 69, The C-terminal domain CTD spans amino acids aa — Neutral NFKB2 variants are shown in black.
EV, empty vector. Data shown are representative of two independent experiments. Statistical comparisons were performed using two-tailed Mann—Whitney U -tests. AD, autosomal dominant. Three of these patients, aged 17, 23 and 39 years, were admitted to intensive care and two of these individuals aged 23 and 39 years died Fig.
Eight additional unvaccinated patients developed asymptomatic disease or mild symptoms NIH scale, 1—2 without pneumonia or hospitalization. All patients with severe varicella were hospitalized, including one with encephalitis and one with severe skin disease requiring acyclovir. The other severe viral diseases observed are indicated in Supplementary Table 1.
