Burden of Oral Symptoms and Health-Related Quality of Life in Long-Term Care Settings in Helsinki, Finland

Objectives Poor oral health may complicate eating and deteriorate nutritional status. However, little is known about how the burden of oral symptoms (OS) is associated with the health-related quality of life (HRQoL) of vulnerable older people in institutional settings. This study explores how the burden of certain OS (chewing problems, swallowing difficulties, dry mouth) is associated with functioning, morbidity, nutritional status and eating habits. It also examines the association between the OS burden and HRQoL. Design A cross-sectional study in 2017. Setting All long-term care wards in Helsinki, Finland. Participants 2401 older residents (74% females, mean age 83.9). Measurements Nurses assessed the residents and completed questionnaires on the participants' demographics, functional status, diagnoses, OS and eating habits. Nutritional status was assessed using the Mini Nutritional Assessment (MNA) and HRQoL with a 15-dimensional instrument (15D). Results Of the residents, 25.4% had one OS and 16.6% two or three OS. OS burden was associated linearly with poorer cognitive and physical functioning and a higher number of comorbidities, edentulousness without dentures, and less frequent teeth brushing/denture cleaning. OS burden was also associated with malnutrition, lower BMI and eating less during main meals. In the multivariate analyses adjusted for various confounding factors, a higher number of OS was associated with lower HRQoL. OS burden correlated with nearly all dimensions of HRQoL. Conclusion Oral symptoms are associated with generic HRQoL. Therefore, OS should be regularly assessed and managed in daily care.Peer reviewe

Concentration Dependence of the Effective Mass of He-3 Atoms in He-3/He-4 Mixtures

Recent measurements by Yorozu et al. (S. Yorozu, H. Fukuyama, and H. Ishimoto, Phys. Rev. B 48, 9660 (1993)) as well as by Simons and Mueller (R. Simons and R. M. Mueller, Czhechoslowak Journal of Physics Suppl. 46, 201 (1976)) have determined the effective mass of He-3 atoms in a He-3/He-4 mixture with great accuracy. We here report theoretical calculations for the dependence of that effective mass on the He-3 concentration. Using correlated basis functions perturbation theory to infinite order to compute effective interactions in the appropriate channels, we obtain good agreement between theory and experiment.Comment: 4 pages, 1 figur

Single Particle and Fermi Liquid Properties of He-3/--He-4 Mixtures: A Microscopic Analysis

We calculate microscopically the properties of the dilute He-3 component in a He-3/--He-4 mixture. These depend on both, the dominant interaction between the impurity atom and the background, and the Fermi liquid contribution due to the interaction between the constituents of the He-3 component. We first calculate the dynamic structure function of a He-3 impurity atom moving in He-3. From that we obtain the excitation spectrum and the momentum dependent effective mass. The pole strength of this excitation mode is strongly reduced from the free particle value in agreement with experiments; part of the strength is distributed over high frequency excitations. Above k > 1.7$\AA$^{-1}$ the motion of the impurity is damped due to the decay into a roton and a low energy impurity mode. Next we determine the Fermi--Liquid interaction between He-4 atoms and calculate the pressure-- and concentration dependence of the effective mass, magnetic susceptibility, and the He-3--He-3 scattering phase shifts. The calculations are based on a dynamic theory that uses, as input, effective interactions provided by the Fermi hypernetted--chain theory. The relationship between both theories is discussed. Our theoretical effective masses agree well with recent measurements by Yorozu et al. (Phys. Rev. B 48, 9660 (1993)) as well as those by R. Simons and R. M. Mueller (Czekoslowak Journal of Physics Suppl. 46, 201 (1996)), but our analysis suggests a new extrapolation to the zero-concentration limit. With that effective mass we also find a good agreement with the measured Landau parameter F_0^a.Comment: 47 pages, 15 figure

Swallowing difficulty and nutrient intakes among residents in assisted living facilities in Helsinki

Background: Swallowing difficulty (SWD) commonly occurs and is associated with malnutrition in old age. Less is known of how SWD is associated with various nutrient intakes. Objectives: To examine how SWD among residents in assisted living facilities. Materials and methods: In this cross-sectional study, we examined 345 residents in Helsinki in 2007. Detailed energy, protein and nutrient intakes were calculated from 1-day food diaries and compared with the Nordic Nutrition Recommendations (NNRs) as a measure of dietary adequacy. Swallowing was assessed by the closest nurse knowing the resident well. Nutritional status was assessed using the Mini-Nutritional Assessment (MNA). Results: Of the participants, 14% (n = 48) suffered from SWD, often had prior stroke, increased comorbidities and lower body-mass index. A larger proportion of residents with SWD consumed oral nutritional supplements. The MNA showed that over 52% of residents with SWD were malnourished, whereas the respective figure was 17% among residents without SWD. A large proportion of the study population had lower than recommended intakes of energy, protein and micronutrients. However, those with SWD differed significantly from those without only in higher protein and lower zinc and folic acid intakes. Conclusion: Although malnutrition was more common among those with SWD than those without, the daily intakes of energy, protein and micronutrients were similar in these groups, highlighting that the risk of malnutrition and low nutrient intakes commonly occurred in both groups of residents in assisted living facilities. (C) 2017 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved.Peer reviewe

Truncating <em>NFKB1 </em>variants cause combined NLRP3 inflammasome activation and type I interferon signaling and predispose to necrotizing fasciitis

\ua9 2024 The AuthorsIn monogenic autoinflammatory diseases, mutations in genes regulating innate immune responses often lead to uncontrolled activation of inflammasome pathways or the type I interferon (IFN-I) response. We describe a mechanism of autoinflammation potentially predisposing patients to life-threatening necrotizing soft tissue inflammation. Six unrelated families are identified in which affected members present with necrotizing fasciitis or severe soft tissue inflammations. Exome sequencing reveals truncating monoallelic loss-of-function variants of nuclear factor κ light-chain enhancer of activated B cells (NFKB1) in affected patients. In patients’ macrophages and in NFKB1-variant-bearing THP-1 cells, activation increases both interleukin (IL)-1β secretion and IFN-I signaling. Truncation of NF-κB1 impairs autophagy, accompanied by the accumulation of reactive oxygen species and reduced degradation of inflammasome receptor nucleotide-binding oligomerization domain, leucine-rich repeat-containing protein 3 (NLRP3), and Toll/IL-1 receptor domain-containing adaptor protein inducing IFN-β (TRIF), thus leading to combined excessive inflammasome and IFN-I activity. Many of the patients respond to anti-inflammatory treatment, and targeting IL-1β and/or IFN-I signaling could represent a therapeutic approach for these patients

Endostatin expression in pancreatic tissue is modulated by elastase

Pancreatic tumours are scirrhous, avascular tumours, suggesting that they may produce angiogenesis inhibitors that suppress the growth of the vasculature to the tumour and metastases. We have sought evidence for the angiogenesis inhibitor, endostatin, in normal and cancerous pancreatic tissue. Using Western blotting, we found mature 20 kDa endostatin in cancer tissue but not in normal tissue. Several endostatin-related peptides of higher mol wt were present in both tissues. Extracts from normal tissue were able to degrade exogenous endostatin, whereas extracts from cancer were without effect. Although the exocrine pancreas secretes inactive proenzymes of trypsin, chymotrypsin and elastase, their possible role in this degradation was examined. The trypsin/chymotrypsin inhibitor, Glycine max, did not prevent the degradation of endostatin by normal pancreatic extracts but elastatinal, a specific inhibitor of elastase, reduced the rate of degradation. Extracts of pancreatic tumours did not express any detectable elastase activity, but an elastase (Km 1.1 mM) was expressed by extracts of normal pancreas. We conclude that endostatin is present and stable in pancreatic cancer tissues, which may explain their avascular nature, but that normal pancreatic tissue expresses enzymes, including elastase, which rapidly degrade endostatin. The stability of endostatin may have implications for its therapeutic use

Novel Hemizygous IL2RG p.(Pro58Ser) Mutation Impairs IL-2 Receptor Complex Expression on Lymphocytes Causing X-Linked Combined Immunodeficiency

Hypomorphic IL2RG mutations may lead to milder phenotypes than X-SCID, named variably as atypical X-SCID or X-CID. We report an 11-year-old boy with a novel c. 172C>T;p.(Pro58Ser) mutation in IL2RG, presenting with atypical X-SCID phenotype. We also review the growing number of hypomorphic IL2RG mutations causing atypical X-SCID. We studied the patient's clinical phenotype, B, T, NK, and dendritic cell phenotypes, IL2RG and CD25 cell surface expression, and IL-2 target gene expression, STAT tyrosine phosphorylation, PBMC proliferation, and blast formation in response to IL-2 stimulation, as well as protein-protein interactions of the mutated IL2RG by BioID proximity labeling. The patient suffered from recurrent upper and lower respiratory tract infections, bronchiectasis, and reactive arthritis. His total lymphocyte counts have remained normal despite skewed T and B cells subpopulations, with very low numbers of plasmacytoid dendritic cells. Surface expression of IL2RG was reduced on his lymphocytes. This led to impaired STAT tyrosine phosphorylation in response to IL-2 and IL-21, reduced expression of IL-2 target genes in patient CD4+ T cells, and reduced cell proliferation in response to IL-2 stimulation. BioID proximity labeling showed aberrant interactions between mutated IL2RG and ER/Golgi proteins causing mislocalization of the mutated IL2RG to the ER/Golgi interface. In conclusion, IL2RG p.(Pro58Ser) causes X-CID. Failure of IL2RG plasma membrane targeting may lead to atypical X-SCID. We further identified another carrier of this mutation from newborn SCID screening, lost to closer scrutiny

Autoimmunity, hypogammaglobulinemia, lymphoproliferation and mycobacterial disease in patients with dominant activating mutations in STAT3

The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of IPEX-like syndrome. Here, we immunologically characterized three patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T and p.K658N, respectively). The patients displayed multi-organ autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4-CD8-) T cells, and decreased NK, Th17, and regulatory T cell numbers. Notably, the patient harboring the K392R mutation developed T cell LGL leukemia at age 14. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of IPEX-like syndrome. Here, we immunologically characterized three patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T and p.K658N, respectively). The patients displayed multi-organ autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4-CD8-) T cells, and decreased NK, Th17, and regulatory T cell numbers. Notably, the patient harboring the K392R mutation developed T cell LGL leukemia at age 14. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of IPEX-like syndrome. Here, we immunologically characterized three patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T and p.K658N, respectively). The patients displayed multi-organ autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4-CD8-) T cells, and decreased NK, Th17, and regulatory T cell numbers. Notably, the patient harboring the K392R mutation developed T cell LGL leukemia at age 14. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of IPEX-like syndrome. Here, we immunologically characterized three patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T and p.K658N, respectively). The patients displayed multi-organ autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4-CD8-) T cells, and decreased NK, Th17, and regulatory T cell numbers. Notably, the patient harboring the K392R mutation developed T cell LGL leukemia at age 14. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of IPEX-like syndrome. Here, we immunologically characterized three patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T and p.K658N, respectively). The patients displayed multi-organ autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4-CD8-) T cells, and decreased NK, Th17, and regulatory T cell numbers. Notably, the patient harboring the K392R mutation developed T cell LGL leukemia at age 14. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of IPEX-like syndrome. Here, we immunologically characterized three patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T and p.K658N, respectively). The patients displayed multi-organ autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4-CD8-) T cells, and decreased NK, Th17, and regulatory T cell numbers. Notably, the patient harboring the K392R mutation developed T cell LGL leukemia at age 14. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of IPEX-like syndrome. Here, we immunologically characterized three patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T and p.K658N, respectively). The patients displayed multi-organ autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4-CD8-) T cells, and decreased NK, Th17, and regulatory T cell numbers. Notably, the patient harboring the K392R mutation developed T cell LGL leukemia at age 14. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of IPEX-like syndrome. Here, we immunologically characterized three patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T and p.K658N, respectively). The patients displayed multi-organ autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4-CD8-) T cells, and decreased NK, Th17, and regulatory T cell numbers. Notably, the patient harboring the K392R mutation developed T cell LGL leukemia at age 14. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of IPEX-like syndrome. Here, we immunologically characterized three patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T and p.K658N, respectively). The patients displayed multi-organ autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4-CD8-) T cells, and decreased NK, Th17, and regulatory T cell numbers. Notably, the patient harboring the K392R mutation developed T cell LGL leukemia at age 14. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of IPEX-like syndrome. Here, we immunologically characterized three patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T and p.K658N, respectively). The patients displayed multi-organ autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4-CD8-) T cells, and decreased NK, Th17, and regulatory T cell numbers. Notably, the patient harboring the K392R mutation developed T cell LGL leukemia at age 14. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of IPEX-like syndrome. Here, we immunologically characterized three patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T and p.K658N, respectively). The patients displayed multi-organ autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4-CD8-) T cells, and decreased NK, Th17, and regulatory T cell numbers. Notably, the patient harboring the K392R mutation developed T cell LGL leukemia at age 14. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of IPEX-like syndrome. Here, we immunologically characterized three patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T and p.K658N, respectively). The patients displayed multi-organ autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4-CD8-) T cells, and decreased NK, Th17, and regulatory T cell numbers. Notably, the patient harboring the K392R mutation developed T cell LGL leukemia at age 14. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of IPEX-like syndrome. Here, we immunologically characterized three patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T and p.K658N, respectively). The patients displayed multi-organ autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4-CD8-) T cells, and decreased NK, Th17, and regulatory T cell numbers. Notably, the patient harboring the K392R mutation developed T cell LGL leukemia at age 14. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of IPEX-like syndrome. Here, we immunologically characterized three patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T and p.K658N, respectively). The patients displayed multi-organ autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4-CD8-) T cells, and decreased NK, Th17, and regulatory T cell numbers. Notably, the patient harboring the K392R mutation developed T cell LGL leukemia at age 14. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of IPEX-like syndrome. Here, we immunologically characterized three patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T and p.K658N, respectively). The patients displayed multi-organ autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4-CD8-) T cells, and decreased NK, Th17, and regulatory T cell numbers. Notably, the patient harboring the K392R mutation developed T cell LGL leukemia at age 14. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of IPEX-like syndrome. Here, we immunologically characterized three patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T and p.K658N, respectively). The patients displayed multi-organ autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4-CD8-) T cells, and decreased NK, Th17, and regulatory T cell numbers. Notably, the patient harboring the K392R mutation developed T cell LGL leukemia at age 14. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.</p