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.

Key Points Germline activating STAT3 mutations were detected in 3 patients with autoimmunity, hypogammaglobulinemia, and mycobacterial disease. T-cell lymphoproliferation, deficiency of regulatory and helper 17 T cells, natural killer cells, dendritic cells, and eosinophils were common.

White blood cells, C-reactive protein and erythrocyte sedimentation rate in pneumococcal pneumonia in children. M. Korppi, T. Heiskanen-Kosma, M. Leinonen. ©ERS Journals Ltd 1997. ABSTRACT: We evaluated the applicability of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell count (WBC), and absolute neutrophil count (ANC), in the screening of pneumococcal (PNC) pneumonia in children.In 1981-1982, 161 children were treated for radiologically verified communityacquired pneumonia in the hospital during a period of 12 months. The Streptococcus pneumoniae aetiology of infection was studied by antigen, antibody and immune complex assays in acute and convalescent sera. In acute blood samples, CRP was measured by the immunonephelometric method, ESR by the Westergren method, WBC using an automatic cell counter, and thereafter the ANC was calculated after microscopic examination of peripheral smears.CRP and ESR were significantly higher in patients with alveolar (n=53) than in those with interstitial (n=108) pneumonia. CRP, ESR and ANC were significantly higher in PNC (n=29) than in viral (n=23) pneumonia. The values in mixed PNC and viral infections (n=17) were approximately midway between PNC and viral cases. All cases with serologic evidence of S. pneumoniae aetiology were combined (n=46) for calculation of diagnostic parameters. When a cut-off limit of 60 mg·L -1 was used, CRP had a sensitivity of 26% and a specificity of 83% in the screening of PNC pneumonia.We conclude that C-reactive protein and erythrocyte sedimentation rate have a limited capacity to differentiate between pneumococcal and nonpneumococcal pneumonia. C-reactive protein is recommended as the first-line method of screening, and the value of 60 mg·L -1 as the cut-off limit. Eur Respir J 1997; 10: 1125-1129

Viral and bacterial antigen and antibody assays were prospectively applied to study the microbial aetiology of community-acquired pneumonia in 195 hospitalised children during a surveillance period of 12 months. A viral infection alone was indicated in 37 (19%), a bacterial infection alone in 30 (15%) and a mixed viral-bacterial infection in 32 (16%) patients. Thus, 46% of the 69 patients with viral infection and 52% of the 62 patients with bacterial infection had a mixed viral and bacterial aetiology. Respiratory syncytial virus (RSV) was identified in 52 patients and Streptococcus pneumoniae in 41 patients. The next common agents in order were non-classified Haemophilus influenzae (17 cases), adenoviruses (10 cases) and Chlamydia species (8 cases). The diagnosis of an RSV infection was based on detecting viral antigen in nasopharyngeal secretions in 79% of the cases. Pneumococcal infections were in most cases identified by antibody assays; in 39% they were indicated by demonstrating pneumococcal antigen in acute phase serum. An alveolar infiltrate was present in 53 (27%) and an interstitial infiltrate in 108 (55%) of the 195 patients. The remaining 34 patients had probable pneumonia. C-reactive protein (CRP), erythrocyte sedimentation rate and total white blood cell count were elevated in 25%, 40% and 36% of the patients, respectively. CRP was more often elevated in patients with bacterial infection alone than in those with viral or mixed viral-bacterial infections. No other correlation was seen between the radiological or laboratory findings and serologically identified viral, bacterial or mixed viral-bacterial infections.(ABSTRACT TRUNCATED AT 250 WORDS)

Incidence of community-acquired pneumonia in children caused byMycoplasma pneumoniae : Serological results of a prospective, population-based study in primary health care KORPPI M, HEISKANEN-KOSMA T, KLEEMOLA M. Respirology 2004; 9 : 109-114 Objective:The objective of the present study was to assess the incidence of community-acquired pneumonia (CAP) in children caused by Mycoplasma pneumoniae . Methodology: During 12 months in 1981-1982, all CAP cases in a defined child population were registered. M. pneumoniae aetiology, initially measured by complement fixation (CF) test, was in 1999 supplemented by measurement of IgG and IgM antibodies using enzyme immunoassays (EIA). Results: M. pneumoniae was detected in 61 (30%) of 201 paediatric CAP cases, being the most common aetiological agent in those 5 years of age or over. At that age, M. pneumoniae was responsible for over 50% of cases, and over 90% of mycoplasmal cases were treated as outpatients. The EIA detected 17 new cases over and above the 44 detected by CF, while CF alone revealed 10 cases. The incidence of M. pneumoniae CAP increased with age, being over 10/1000 children at the age of 10 years or more. Co-infections with Streptococcus pneumoniae and Chlamydia pneumoniae were present in over 30% and 15%, respectively, of mycoplasmal CAP cases. Conclusion: M. pneumoniae is a common cause of paediatric CAP in primary health care, and coinfections with S. pneumoniae are common. Both S. pneumoniae and M. pneumoniae should be taken into account when starting antibiotics for children with CAP.