Herpes Simplex Encephalitis Does Interferon Care?

Introduction and aims: Herpes simplex encephalitis (HSE) is an acute, life-threatening disease, requiring prompt intervention. TLR3-interferon (IFN) axis defects in the antiviral innate immune response against HSV-1 and some genes (TLR3, UNC93B1 and TRAF3) probably play an important role in HSE pathogenesis. Methods: Descriptive study between January 2007 and December 2012 from HSE patients treated with acyclovir (initiated between D2 to D3 of illness) and INF alpha-2b. HSV-1 was detected by PCR from CSF. PBMC and fibroblasts were studied for their IFN responses to TLR3 and virus stimulations. Coding exons of the known HSE-associated genes were sequenced. Results: Six cases, aged between 7 months and 11 years, with seizures and extensive brain injury. Interferon was initiated between D3 and D18. Patient 1 initiated IFN on D18 and stopped 7 days later for bicytopenia. Patient 2 started on D3 and has no sequelae. Patient 4 started on D5 and has persistent right sided hemiparesis. Patient 3, 5 and 6 started on D5, D3 and D7 respectively remain with epilepsy under medical control. Only Patient 1, who started IFN later than D7, has sequelar tetraparesis. None of the other patients have severe neurological deficits. The functional studies were normal, except for patient 1 whose fibroblasts displayed impaired IFN-lambda production after stimulations of poly(I:C), thought to be TLR3-dependent. No mutation was found in the sequenced coding exons of UNC93B1, TLR3 and TRAF3. Conclusions: Although a small sample, our results suggest that IFN therapy should be considered in the treatment of HSE.info:eu-repo/semantics/publishedVersio

A Novel TRAF3IP2 Mutation Causing Chronic Mucocutaneous Candidiasis

Inborn errors of the IL-17-mediated signaling have been associated with chronic mucocutaneous candidiasis (CMC). We describe a patient with CMC, atopic dermatitis, enamel dysplasia, and recurrent parotitis harboring a novel compound heterozygous mutation of TRAF3IP2, leading to autosomal recessive ACT1 deficiency and deficient IL-17 signaling.info:eu-repo/semantics/publishedVersio

Prevalencia de depresión y ansiedad y variables asociadas en gestantes de Bucaramanga y Floridablanca (Santander, Colombia)

Abstract Introduction. Depression and anxiety are frequent conditions in women of childbearing age and are associated with adverse perinatal outcomes. The prevalence in Colombian population of low obstetric risk is unknown. Objective. Establish the prevalence of depression and gestational anxiety, and the associated demographic, psychosocial and clinical variables, in women attending prenatal care in Bucaramanga and Floridablanca, Santander. Methodology. A cross-sectional, descriptive study applying a survey and Edinburgh Postnatal Depression Scales, Zung Anxiety Self-Assessment, family apgar and perceived social support questionnaire. The prevalence ratios were established with 95% confidence intervals. Results. A total of 244 pregnant women were studied, with an average of 24.8 years. The prevalence of depression was 24.6%, 95% CI (19.1-30.0) and anxiety was 25.8%, 95% CI (20.3-31.3). Depression is associated with a family history of depression in first or second degree, prevalence ratio: 2.0, 95% CI (1.1-3.7); presence of anxiety, prevalence ratio: 22.5, 95% CI (9.4-53.7); and alcohol consumption, prevalence ratio: 2.9, 95% CI (1.1-8.2). A protective factor was found to have two sources of income (couple and family), prevalence ratio: 0.6, 95% CI (0.4-0.8). Additionally, anxiety was associated with the presence of depression, prevalence ratio: 13.3, 95% CI (6.3-28.1); presence of psychological violence, prevalence ratio: 2.3, 95% CI (1.1-4.8) and trusting the couple, prevalence ratio: 3.4, 95% CI (1.5-8.2). Conclusion. There is a strong association between anxiety and depression so it should be screened during pregnancy. Keywords: Pregnancy; Depression; Anxiety; Prevalence; Risk factors.Introducción. La depresión y la ansiedad son condiciones frecuentes en la mujer en edad fértil y están asociadas a desenlaces perinatales adversos. Se desconoce la prevalencia en población colombiana de bajo riesgo obstétrico. Objetivo. Determinar la prevalencia de depresión y ansiedad gestacional, y las variables demográficas, psicosociales y clínicas asociadas, en mujeres consultantes a control prenatal en Bucaramanga y Floridablanca, Santander. Metodología. Estudio descriptivo, transversal aplicando una encuesta y las escalas de Depresión Posnatal de Edimburgo, autoevaluación de ansiedad de Zung, apgar familiar y cuestionario de apoyo social percibido. Se establecieron las razones de prevalencia con intervalos de confianza del 95%. Resultados. Se estudiaron 244 gestantes, con un promedio de 24.8 años. La prevalencia de depresión fue de 24.6%, IC 95% (19.1-30.0) y ansiedad fue de 25.8%, IC 95% (20.3-31.3). La depresión está asociada con antecedente familiar de depresión en primer o segundo grado, razón de prevalencia: 2.0, IC 95% (1.1-3.7); presencia de ansiedad, razón de prevalencia: 22.5, IC 95% (9.4-53.7); y consumo de alcohol, razón de prevalencia: 2.9, IC 95% (1.1-8.2). Como factor protector se encontró tener dos fuentes de ingresos (pareja y familia), razón de prevalencia: 0.6, IC 95% (0.4-0.8). Adicionalmente, la ansiedad se asoció a presencia de depresión, razón de prevalencia: 13.3, IC 95% (6.3-28.1); presencia de violencia psicológica, razón de prevalencia: 2.3, IC 95% (1.1-4.8) y tener confianza en la pareja, razón de prevalencia: 3.4, IC 95% (1.5-8.2). Conclusión. Existe una fuerte asociación entre ansiedad y depresión por lo que debe ser tamizada durante la gestación. &nbsp

International Union of Immunological Societies: 2017 Primary Immunodeficiency Diseases Committee Report on Inborn Errors of Immunity

Beginning in 1970, a committee was constituted under the auspices of the World Health Organization (WHO) to catalog primary immunodeficiencies. Twenty years later, the International Union of Immunological Societies (IUIS) took the remit of this committee. The current report details the categorization and listing of 354 (as of February 2017) inborn errors of immunity. The growth and increasing complexity of the field have been impressive, encompassing an increasing variety of conditions, and the classification described here will serve as a critical reference for immunologists and researchers worldwide

Lymphadenopathy after BCG vaccination in a child with chronic granulomatous disease

We report a 15-month-old boy who developed an ulcer in the left axillary fold following bacillus Calmette-Guerin vaccination. Subsequent immunologic and genetic studies led to the diagnosis of chronic granulomatous disease. His mother had "lupus-like" lesions, described in some carriers of this disease, that were thus related to her son's diagnosis. Although in healthy subjects this vaccination is usually harmless, in instances of impaired immunity it may cause adverse reactions. When a vaccine-related complication occurs, an underlying immunodeficiency should be sough

Family Relationship, Water Contact and Occurrence of Buruli Ulcer in Benin

Mycobacterium ulcerans disease (Buruli ulcer) is the most widespread mycobacterial disease in the world after leprosy and tuberculosis. How M. ulcerans is introduced into the skin of humans remains unclear, but it appears that individuals living in the same environment may have different susceptibilities. This case control study aims to determine whether frequent contacts with natural water sources, family relationship or the practice of consanguineous marriages are associated with the occurrence of Buruli ulcer (BU). The study involved 416 participants, of which 104 BU-confirmed cases and 312 age, gender and village of residence matched controls (persons who had no signs or symptoms of active or inactive BU). The results confirmed that contact with natural water sources is a risk factor. Furthermore, it suggests that a combination of genetic factors may constitute risk factors for the development of BU, possibly by influencing the type of immune response in the individual, and, consequently, the development of BU infection per se and its different clinical forms. These findings may be of major therapeutic interest

The intersection of COVID-19 and autoimmunity

Acute coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is characterized by diverse clinical presentations, ranging from asymptomatic infection to fatal respiratory failure, and often associated with varied longer-term sequelae. Over the past 18 months, it has become apparent that inappropriate immune responses contribute to the pathogenesis of severe COVID-19. Researchers working at the intersection of COVID-19 and autoimmunity recently gathered at an American Autoimmune Related Disease Association (AARDA) Noel R. Rose Colloquium to address the current state of knowledge regarding two important questions: Does established autoimmunity predispose to severe COVID-19? And, at the same time, can SARS-CoV-2 infection trigger de novo autoimmunity? Indeed, work to date has demonstrated that 10 to 15% of patients with critical COVID-19 pneumonia exhibit autoantibodies against type I interferons, suggesting that preexisting autoimmunity underlies severe disease in some patients. Other studies have identified functional autoantibodies following infection with SARS-CoV-2, such as those that promote thrombosis or antagonize cytokine signaling. These autoantibodies may arise from a predominantly extrafollicular B cell response that is more prone to generating autoantibody-secreting B cells. This review highlights the current understanding, evolving concepts, and unanswered questions provided by this unique opportunity to determine mechanisms by which a viral infection can be exacerbated by, and even trigger, autoimmunity. The potential role of autoimmunity in post-acute sequelae of COVID-19 is also discussed

Iron and risk of dementia: Mendelian randomisation analysis in UK Biobank

This is the final version. Available on open access from BMJ Publishing Group via the DOI in this recordData availability statement: Results are available in a public, open access repository. Access to UK Biobank participant level data requires application. UKB data are available to any bone fide researcher following application (https://www.ukbiobank.ac.uk/enable-your-research/apply-for-access). Summary statistics for these GWAS are available to download from FigShare (DOI 10.6084/m9.figshare.21828498).Background Brain iron deposition is common in dementia, but whether serum iron is a causal risk factor is unknown. We aimed to determine whether genetic predisposition to higher serum iron status biomarkers increased risk of dementia and atrophy of grey matter. Methods We analysed UK Biobank participants clustered into European (N=451284), African (N=7477) and South Asian (N=9570) groups by genetic similarity to the 1000 genomes project. Using Mendelian randomisation methods, we estimated the association between genetically predicted serum iron (transferrin saturation [TSAT] and ferritin), grey matter volume and genetic liability to clinically defined dementia (including Alzheimer’s disease [AD], non-AD dementia, and vascular dementia) from hospital and primary care records. We also performed time-to-event (competing risks) analysis of the TSAT polygenic score on risk of clinically defined non-AD dementia. Results In Europeans, higher genetically predicted TSAT increased genetic liability to dementia (Odds Ratio [OR]: 1.15, 95% Confidence Intervals [CI] 1.04 to 1.26, p=0.0051), non-AD dementia (OR: 1.27, 95% CI 1.12 to 1.45, p=0.00018) and vascular dementia (OR: 1.37, 95% CI 1.12 to 1.69, p=0.0023), but not AD (OR: 1.00, 95% CI 0.86 to 1.15, p=0.97). Higher TSAT was also associated with increased risk of non-AD dementia in participants of African, but not South Asian groups. In survival analysis using a TSAT polygenic score, the effect was independent of apolipoprotein-E ε4 genotype (with adjustment subdistribution Hazard Ratio: 1.74, 95% CI 1.33 to 2.28, p=0.00006). Genetically predicted TSAT was associated with lower grey matter volume in caudate, putamen and thalamus, and not in other areas of interest. Discussion Genetic evidence supports a causal relationship between higher TSAT and risk of clinically defined non-AD and vascular dementia, in European and African groups. This association appears to be independent of apolipoprotein-E ε4.National Institute for Health and Care Research (NIHR