Monogenic causes of autoimmunity give key insights to the complex regulation of the immune system. We report a new monogenic cause of autoimmunity resulting from de novo germline activating STAT3 mutations in 5 individuals with a spectrum of early-onset autoimmune disease including type 1 diabetes. These findings emphasise the critical role of STAT3 in autoimmune disease and contrast with the germline inactivating STAT3 mutations that result in Hyper IgE syndrome.

Background: Social distancing measures are used to reduce the spreading of infection. Our aim was to assess the immediate effects of national lockdown orders due to coronavirus disease 2019 (COVID-19) on pediatric emergency room (ER) visits and respiratory tract infections in hospitals and nationwide in Finland. Methods: This register-based study used hospital patient information systems and the Finnish national infectious disease register. The participants were all patients visiting pediatric ER in 2 Finnish hospitals (Kuopio University Hospital, Mikkeli Central Hospital) covering 1/5th of the Finnish children population, 4 weeks before and 4 weeks after the start of the nationwide lockdown on March 16, 2020. Nationwide weekly numbers of influenza (A + B) and respiratory syncytial virus (RSV) in children were assessed from the infectious disease register from 2015 to 2020. Results: A major decrease in the rate of daily median pediatric ER visits was detected in both hospitals in the study during the nationwide lockdown compared with the study period before the lockdown (Mikkeli, 19 vs. 7, P < 0.001; Kuopio, 9 vs. 2,5, P < 0.001). The influenza season was shorter (8 weeks from peak to no cases), and the weekly rate of new cases decreased faster compared with the previous 4 influenza seasons (previously 15–20 weeks from peak to no cases). A similar decrease was also seen in RSV cases. No pediatric cases of COVID-19 were found in participating hospitals during the study period. Conclusion: These results strongly suggest that social distancing and other lockdown strategies are effective to slow down the spreading of common respiratory viral diseases and decreasing the need for hospitalization among children.

• Diverse patient groups with GATA2 mutation develop mononuclear cytopenia and elevated Flt3 ligand. • Progressive cytopenias, risingFlt3 ligand, and terminal differentiation of lymphoid cells accompany clinical progression.Constitutive heterozygous GATA2 mutation is associated with deafness, lymphedema, mononuclear cytopenias, infection, myelodysplasia (MDS), and acute myeloid leukemia. In this study, we describe a cross-sectional analysis of 24 patients and 6 relatives with 14 different frameshift or substitution mutations of GATA2. A pattern of dendritic cell, monocyte, B, and natural killer (NK) lymphoid deficiency (DCML deficiency) with elevated Fms-like tyrosine kinase 3 ligand (Flt3L) was observed in all 20 patients phenotyped, including patients with Emberger syndrome, monocytopenia with Mycobacterium avium complex (MonoMAC), and MDS. Four unaffected relatives had a normal phenotype indicating that cellular deficiency may evolve over time or is incompletely penetrant, while 2 developed subclinical cytopenias or elevated Flt3L. Patients with GATA2 mutation maintained higher hemoglobin, neutrophils, and platelets and were younger than controls with acquired MDS and wild-type GATA2. Frameshift mutations were associated with earlier age of clinical presentation than substitution mutations. Elevated Flt3L, loss of bone marrow progenitors, and clonal myelopoiesis were early signs of disease evolution. Clinical progression was associated with increasingly elevated Flt3L, depletion of transitional B cells, CD56 bright NK cells, naïve T cells, and accumulation of terminally differentiated NK and CD8 1 memory T cells. These studies provide a framework for clinical and laboratory monitoring of patients with GATA2 mutation and may inform therapeutic decision-making. (Blood. 2014;123(6):863-874)

The results of our prospective, strictly population-based study confirm the importance of S. pneumoniae in the etiology of community-acquired pneumonia in children of all ages. M. pneumoniae and Chlamydia pneumoniae are important from the age of 5 years onwards.