Overt immune activation by viral infections can lead to cytokine storm syndromes, such as hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS). We aimed to compare the imm Show more
Overt immune activation by viral infections can lead to cytokine storm syndromes, such as hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS). We aimed to compare the immune response to different viral pathogens to understand the connection between infections and cytokine storm syndromes. We recruited children who sought care at the emergency department with fever for ≥3 days. We performed immune profiling using Olink proximity extension assay and flow cytometry. We compared the findings with cases of HLH, MAS, Kawasaki disease (KD), and multisystem inflammatory syndrome in children (MIS-C). We enrolled 352 febrile patients and studied 110 cases of confirmed common viral infections. We found that Epstein-Barr virus (EBV) uniquely triggered high levels of multiple cytokines (IL-18, IL-27, TNF, FLT3 ligand, and lymphotoxin alpha) and IFN-γ-induced chemokines (CXCL9/10/11 and CCL19). These patterns are similar to the hyperinflammatory response associated with HLH/MAS but are less consistent with the findings in KD and MIS-C. Flow cytometry analysis revealed that CD38 This work broadens our understanding of common viral infections in children and provides an immunologic basis for the link between EBV infection and HLH/MAS. Show less
Weilai Dong, Sheng Chih Jin, Michael C Sierant+36 more · 2025 · Proceedings of the National Academy of Sciences of the United States of America · National Academy of Sciences · added 2026-04-24
Variants with large effect contribute to congenital heart disease (CHD). To date, recessive genotypes (RGs) have commonly been implicated through anecdotal ascertainment of consanguineous families and Show more
Variants with large effect contribute to congenital heart disease (CHD). To date, recessive genotypes (RGs) have commonly been implicated through anecdotal ascertainment of consanguineous families and candidate gene-based analysis; the recessive contribution to the broad range of CHD phenotypes has been limited. We analyzed whole exome sequences of 5,424 CHD probands. Rare damaging RGs were estimated to contribute to at least 2.2% of CHD, with greater enrichment among laterality phenotypes (5.4%) versus other subsets (1.4%). Among 108 curated human recessive CHD genes, there were 66 RGs, with 54 in 11 genes with >1 RG, 12 genes with 1 RG, and 85 genes with zero. RGs were more prevalent among offspring of consanguineous union (4.7%, 32/675) than among nonconsanguineous probands (0.7%, 34/4749). Founder variants in Show less