ABSTRACT
OBJECTIVE: Primary ciliary dyskinesia (PCD) severity has been related to genotype and levels of nasal nitric oxide (nNO). The most common TAS2R38 haplotypes (PAV/PAV, PAV/AVI, AVI/AVI) encoding the bitter taste receptor can affect nNO levels and thus could play a role in the susceptibility to respiratory infections. We assessed the impact of these polymorphisms on nNO production and Pseudomonas aeruginosa (P.a.) infections in different PCD genotypes. METHODS: Prospective, longitudinal, single-centre study in patients with PCD with known genotype and one of three TAS2R38 haplotypes evaluated for up to 10 years. We related nNO values to TAS2R38 haplotypes in all patients, and in the three most frequent genotypes (CCDC39/CCDC40, DNAH5, DNAH11). In the genetic group(s) with different mean trends of nNO in relation to the polymorphism, we evaluated longitudinal lung function as a clinical outcome measure. We also studied any associations between the prevalence of chronic P.a. infection and PAV alleles. Linear mixed-effects models were used to evaluate longitudinal associations. RESULTS: 119 patients with PCD underwent 1116 study visits. Only in the DNAH11 mutations group was there a mean trend of nNO production which was significantly higher in PAV/PAV than AVI/AVI haplotype (p=0.033), with a better trend in spirometric and plethysmographic parameters. In patients with DNAH11 mutations the PAV allele was also associated with a significantly reduced prevalence of chronic P.a. CONCLUSION: TAS2R38 may be a modifier gene for PCD severity, but only in mild phenotype disease. Further study of TAS2R38 polymorphisms might enable new management strategies to prevent chronic P.a.
ABSTRACT
Behçet's Disease (BD), also recognized as Behçet Syndrome, manifests uniquely in pediatric populations as Pediatric Behçet's Disease (PBD), characterized by multisystemic inflammatory symptoms including recurrent oral and genital aphthae, and diverse ocular, vascular, and neurological involvements. This review elucidates the prevalence, burden, and management strategies of headaches in children with PBD, focusing on both primary headaches, such as migraine and tension-type headaches, and secondary headaches linked to systemic disease manifestations. It explores the pathophysiological underpinnings specific to PBD-related headaches and discusses the intricate relationship between systemic inflammatory processes and neurological symptoms. By examining the literature from 2004 to 2024, this study highlights the high frequency of headache in PBD patients, underscoring its diagnostic and clinical significance. We aim to provide a detailed understanding of headache management in PBD, emphasizing tailored therapeutic strategies that address the unique challenges faced by this patient population. This review also underscores the importance of comprehensive clinical evaluations to optimize outcomes and mitigate long-term sequelae, proposing that awareness and understanding of headache in PBD can significantly enhance both diagnosis and management.
ABSTRACT
This systematic review and meta-analysis aimed to consolidate evidence on dietary interventions for atopic eczema/dermatitis (AD) skin symptoms in children without food allergies, following PRISMA 2020 guidelines. Systematic review updates were conducted in May 2022 and June 2023, focusing on randomized placebo-controlled trials (RCTs) involving children with AD but without food allergies. Specific diets or supplements, such as vitamins, minerals, probiotics, prebiotics, symbiotics, or postbiotics, were explored in these trials. Exclusions comprised descriptive studies, systematic reviews, meta-analyses, letters, case reports, studies involving elimination diets, and those reporting on food allergens in children and adolescents. Additionally, studies assessing exacerbation of AD due to food allergy/sensitization and those evaluating elimination diets' effects on AD were excluded. Nutritional supplementation studies were eligible regardless of sensitization profile. Evaluation of their impact on AD clinical expression was performed using SCORAD scores, and a meta-analysis of SCORAD outcomes was conducted using random-effect models (CRD42022328702). The review encompassed 27 RCTs examining prebiotics, Vitamin D, evening primrose oil, and substituting cow's milk formula with partially hydrolyzed whey milk formula. A meta-analysis of 20 RCTs assessing probiotics, alone or combined with prebiotics, revealed a significant reduction in SCORAD scores, suggesting a consistent trend in alleviating AD symptoms in children without food allergies. Nonetheless, evidence for other dietary interventions remains limited, underscoring the necessity for well-designed intervention studies targeting multiple factors to understand etiological interactions and propose reliable manipulation strategies.
Subject(s)
Dermatitis, Atopic , Randomized Controlled Trials as Topic , Child , Humans , Dermatitis, Atopic/diet therapy , Dermatitis, Atopic/therapy , Dietary Supplements , Prebiotics/administration & dosage , Probiotics/administration & dosage , Probiotics/therapeutic useABSTRACT
Chronic infantile neurological cutaneous articular (CINCA) syndrome is an autoinflammatory disease encompassed in the group of cryopyrin-associated periodic syndromes (CAPS). Patients suffering from CINCA have an elevated risk of developing chronic sequelae, including deforming arthropathy, chronic meningitis, neurodevelopmental delay, and neurosensorial hearing loss. The diagnosis of CINCA presents several difficulties, as the clinical phenotype could be difficult to recognize, and almost half of the patients have negative genetic testing. In this paper, we describe the case of a patient presenting with the typical phenotype of neonatal-onset CINCA who resulted negative for NLRP3 mutations. Based on the clinical judgment, the patient underwent treatment with anti-interleukin-1 (IL-1) agents (anakinra and, later, canakinumab) resulting in a complete clinical and laboratory response that allowed confirmation of the diagnosis. Additional genetic investigations performed after the introduction of anti-IL-1 therapy revealed a pathogenic mosaicism in the NLRP3 gene. After a 12-year follow-up, the patient has not experienced chronic complications. Although genetics is rapidly progressing, this case highlights the importance of early diagnosis of CINCA patients when the clinical and laboratory picture is highly suggestive in order to start the appropriate anti-cytokine treatment even in the absence of a genetic confirmation.
ABSTRACT
The adaptor protein 4 (AP-4) constitutes a conserved hetero-tetrameric complex within the family of adaptor protein (AP) complex, crucial for the signal-mediated trafficking of integral membrane proteins. Mutations affecting all subunits of the AP-4 complex have been linked to autosomal-recessive cerebral palsy and a complex hereditary spastic paraparesis (HSP) phenotype. Our report details the case of a 14-year-old boy born to consanguineous parents, presenting psychomotor delay, severe intellectual disability, microcephaly, and trigonocephaly. Despite a history of febrile seizures, subsequent years were devoid of seizures, with normal EEG. Exome sequencing revealed pathogenic variants in both the AP4B1 and ERF genes. Significantly, the patient exhibited features associated with AP4B1 mutations, including distinctive traits such as cranial malformations. The ERF gene variant, linked to craniosynostosis, likely contributes to the observed trigonocephaly. This case represents the initial documentation of a concurrent mutation in the AP4B1 and ERF genes, underscoring the critical role of exome analysis in unraveling complex phenotypes. Understanding these complex genotypes offers valuable insights into broader syndromic conditions, facilitating comprehensive patient management.
Subject(s)
Adaptor Protein Complex 4 , Mutation , Peptide Termination Factors , Phenotype , Repressor Proteins , Humans , Male , Adolescent , Peptide Termination Factors/genetics , Adaptor Protein Complex 4/genetics , Intellectual Disability/genetics , Intellectual Disability/pathology , Exome Sequencing , Microcephaly/genetics , Microcephaly/pathology , Craniosynostoses/genetics , Craniosynostoses/pathologyABSTRACT
OBJECTIVES: To compare Kawasaki disease (KD) and multisystem inflammatory syndrome (MIS-C) in children. METHODS: Prospective collection of demographics, clinical and treatment data. Assessment of type 1 interferon (IFN) score, CXCL9, CXCL10, Interleukin (IL)18, IFNγ, IL6, IL1b at disease onset and at recovery. RESULTS: 87 patients (43 KD, 44 MIS-C) were included. Age was higher in MIS-C compared to KD group (mean 31±23 vs. 94±50 months, p<0.001). Extremities abnormalities (p=0.027), mucosal involvement (p<0.001), irritability (p<0.001), gallbladder hydrops (p=0.01) and lymphadenopathy (p=0.07) were more often recorded in KD. Neurological findings (p=0.002), gastrointestinal symptoms (p=0.013), respiratory involvement (p=0.019) and splenomegaly (p=0.026) were more frequently observed in MIS-C. Cardiac manifestations were higher in MIS-C (p<0.001), although coronary aneurisms were more frequent in KD (p=0.012). In the MIS-C group, the multiple linear regression analysis revealed that a higher IFN score at onset was related to myocardial disfunction (p<0.001), lymphadenopathy (p=<0.001) and need of ventilation (p=0.024). Both CXCL9 and CXCL10 were related to myocardial disfunction (p<0.001 and p=0.029). IL18 was positively associated to PICU admission (0.030) and ventilation (p=004) and negatively associated to lymphadenopathy (0.004). IFNγ values were related to neurological involvement and lymphadenopathy (p<0.001), IL1b to hearth involvement (0.006). A negative correlation has been observed between IL6 values, heart involvement (p=0.013) and PICU admission (p<0.001). CONCLUSIONS: The demographic and clinical differences between KD e MIS-C cohorts confirm previous reported data. The assessment of biomarkers levels at MIS-C onset could be useful to predict a more severe disease course and the development of cardiac complications.
Subject(s)
COVID-19/complications , Mucocutaneous Lymph Node Syndrome , Systemic Inflammatory Response Syndrome , Humans , Mucocutaneous Lymph Node Syndrome/diagnosis , Mucocutaneous Lymph Node Syndrome/complications , Mucocutaneous Lymph Node Syndrome/epidemiology , Mucocutaneous Lymph Node Syndrome/physiopathology , Male , Female , Child, Preschool , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/epidemiology , Child , Prospective Studies , Infant , COVID-19/diagnosis , Biomarkers/bloodABSTRACT
BACKGROUND: Cyclophilins are ubiquitous panallergens whose epidemiologic, diagnostic, and clinical relevance is largely unknown and whose sensitization is rarely examined in routine allergy practice. OBJECTIVE: We investigated the epidemiologic, diagnostic, and clinical relevance of cyclophilins in seasonal allergic rhinitis and its comorbidities. METHODS: We examined a random sample of 253 (25%) of 1263 Italian children with seasonal allergic rhinitis from the Panallergens in Pediatrics (PAN-PED) cohort with characterized disease phenotypes. Nested studies of sensitization prevalence, correlation, and allergen extract inhibition were performed in patients sensitized to birch pollen extract but lacking IgE to Bet v 1/2/4 (74/1263) or with highest serum level of IgE to Bet v 1 (26/1263); and in patients with sensitization to various extracts (ragweed, mugwort, pellitory, Plantago, and plane tree), but not to their respective major allergenic molecule, profilins, and polcalcins. IgE to cyclophilin was detected with recombinant Bet v 7, and extract inhibition tests were performed with the same rBet v 7. RESULTS: IgE to rBet v 7 was detected in 43 (17%) of 253 patients. It was associated with asthma (P < .028) and oral allergy syndrome (P < .017) in univariate but not multivariate analysis adjusted for IgE to profilins (Phl p 12), PR-10s (Bet v 1), and lipid transfer proteins (Pru p 3). IgE to rBet v 7 was also highly prevalent (47/74, 63%) among patients with unexplained sensitization to birch pollen extract. In patients with unexplained sensitization to ragweed, mugwort, pellitory, Plantago and plane tree pollen, the levels of IgE to those extracts correlated with the levels of IgE to rBet v 7, and they were also significantly inhibited by rBet v 7 (inhibition range 45%-74%). CONCLUSIONS: IgE sensitization to cyclophilin is frequent in pollen-allergic patients living in temperate areas and can produce "false" positive outcomes in skin prick and IgE tests to pollen extracts. Molecular diagnostic guidelines should include this panallergen family.
Subject(s)
Allergens , Cyclophilins , Immunoglobulin E , Pollen , Rhinitis, Allergic, Seasonal , Humans , Immunoglobulin E/immunology , Immunoglobulin E/blood , Child , Rhinitis, Allergic, Seasonal/immunology , Rhinitis, Allergic, Seasonal/epidemiology , Rhinitis, Allergic, Seasonal/diagnosis , Rhinitis, Allergic, Seasonal/blood , Male , Female , Cyclophilins/immunology , Allergens/immunology , Pollen/immunology , Adolescent , Child, Preschool , Antigens, Plant/immunology , Italy/epidemiology , PrevalenceABSTRACT
Asthma is one of the most common non-communicable diseases, and its prevalence and morbidity are influenced by a wide array of factors that are only partially understood. In addition to individual predisposition linked to genetic background and early life infections, environmental factors are crucial in determining the impact of asthma both on an individual patient and on a population level.Several studies have examined the role of the environment where asthmatic subjects live in the pathogenesis of asthma. This review aims to investigate the differences in the prevalence and characteristics of asthma between the pediatric population residing at higher altitudes and children living at lower altitudes, trying to define factors that potentially determine such differences. For this purpose, we reviewed articles from the literature concerning observational studies assessing the prevalence of pediatric asthma in these populations and its characteristics, such as spirometric and laboratory parameters and associated sensitization to aeroallergens.Despite the heterogeneity of the environments examined, the hypothesis of a beneficial effect of residing at a higher altitude on the prevalence of pediatric asthma could be confirmed, as well as a good profile on airway inflammation in asthmatic children. However, the possibility of a higher hospitalization risk for asthma in children living at higher altitudes was demonstrated. Moreover, a positive association between residing at a higher altitude and sensitization to pollens and between lower altitude and sensitization to house dust mites could be confirmed in some pediatric patients, even if the results are not homogeneous, probably due to the different geographical and climatic regions considered. Nonetheless, further studies, e.g., extensive and international works, need to be conducted to better understand the complex interplay between different environmental factors, such as altitude, and the pathogenesis of asthma and how its prevalence and characteristics could vary due to climate change.
Subject(s)
Altitude , Asthma , Humans , Child , Asthma/epidemiology , Asthma/etiology , Genotype , Geography , HospitalizationABSTRACT
BACKGROUND: Long-term health outcomes in children and young people (CYP) after COVID-19 infection are not well understood and studies with control groups exposed to other infections are lacking. This study aimed to investigate the incidence of post-COVID-19 condition (PCC) and incomplete recovery in CYP after hospital discharge and compare outcomes between different SARS-CoV-2 variants and non-SARS-CoV-2 infections. METHODS: A prospective exposure-stratified cohort study of individuals under 18 years old in Moscow, Russia. Exposed cohorts were paediatric patients admitted with laboratory-confirmed COVID-19 infection between April 2 and December 11, 2020 (Wuhan variant cohort) and between January 12 and February 19, 2022 (Omicron variant cohort). CYP admitted with respiratory and intestinal infections, but negative lateral flow rapid diagnostic test and PCR-test results for SARS-CoV-2, between January 12 and February 19, 2022, served as unexposed reference cohort. Comparison between the 'exposed cohorts' and 'reference cohort' was conducted using 1:1 matching by age and sex. Follow-up data were collected via telephone interviews with parents, utilising the long COVID paediatric protocol and survey developed by the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC). The WHO case definition was used to categorise PCC. RESULTS: Of 2595 CYP with confirmed COVID-19, 1707 (65.7%) participated in follow-up interviews, with 1183/1707 (69%) included in the final 'matched' analysis. The median follow-up time post-discharge was 6.7 months. The incidence of PCC was significantly higher in the Wuhan variant cohort (89.7 cases per 1000 person-months, 95% CI 64.3-120.3) compared to post-infection sequalae in the reference cohort (12.2 cases per 1000 person-months, 95% CI 4.9-21.9), whereas the difference with the Omicron variant cohort and reference cohort was not significant. The Wuhan cohort had higher incidence rates of dermatological, fatigue, gastrointestinal, sensory, and sleep manifestations, as well as behavioural and emotional problems than the reference cohort. The only significant difference between Omicron variant cohort and reference cohort was decreased school attendance. When comparing the Wuhan and Omicron variant cohorts, higher incidence of PCC and event rates of fatigue, decreased physical activity, and deterioration of relationships was observed. The rate of incomplete recovery was also significantly higher in the Wuhan variant cohort than in both the reference and the Omicron variant cohorts. CONCLUSIONS: Wuhan variant exhibited a propensity for inducing a broad spectrum of physical symptoms and emotional behavioural changes, suggesting a pronounced impact on long-term health outcomes. Conversely, the Omicron variant resulted in fewer post-infection effects no different from common seasonal viral illnesses. This may mean that the Omicron variant and subsequent variants might not lead to the same level of long-term health consequences as earlier variants.
Subject(s)
COVID-19 , Post-Acute COVID-19 Syndrome , Humans , Child , Adolescent , Moscow/epidemiology , Incidence , Prospective Studies , SARS-CoV-2 , COVID-19/epidemiology , Aftercare , Cohort Studies , Pandemics , Patient Discharge , Chronic Disease , FatigueABSTRACT
BACKGROUND: Even though the incidence of Multisystem Inflammatory Syndrome in children (MIS-C) is decreasing cases are still reported across the world. Studying the consequences of MIS-C enhances our understanding of the disease's prognosis. The objective of this study was to assess short- and medium-term clinical outcomes of MIS-C. METHODS: Prospective observational cohort study at Municipal Children's Hospital Morozovskaya, Moscow, Russia. All children meeting the Royal College of Paediatrics and Child Health (RCPCH), Centers for Disease Control and Prevention (CDC), or the World Health Organization (WHO) MIS-C case definition admitted to the hospital between 17 May and 26 October 2020 were included in the study. All survivors were invited to attend a clinic at 2 and 6 weeks after hospital discharge. RESULTS: 37 children median age 6 years (interquartile range [IQR] 3.3-9.4), 59.5% (22/37) boys were included in the study. 48.6% (18/37) of patients required ICU care. One child died. All children had increased levels of systemic inflammatory markers during the acute event. Echocardiographic investigations identified abnormal findings in 35.1% (13/37) of children. 5.6% (2/36) of children were presenting with any symptoms six weeks after discharge. By six weeks the inflammatory markers were within the reference norms in all children. The echocardiographic evaluation showed persistent coronary dilatation in one child. CONCLUSIONS: Despite the severity of their acute MIS-C, the majority of children in our cohort fully recovered with none having elevated laboratory markers of inflammation at 6 weeks, few (< 10%) reporting persistent symptoms at 6 weeks, and only one with persistent echocardiographic abnormalities.
Subject(s)
COVID-19 , Connective Tissue Diseases , Child , Humans , Male , Prospective Studies , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/therapy , Female , Child, PreschoolABSTRACT
BACKGROUND: IgE antibodies to cross-reactive carbohydrate determinants (CCD) are usually clinically irrelevant but they can be a cause of false positive outcomes of allergen-specific IgE tests in vitro. Their prevalence and levels have been so far cross-sectionally examined among adult allergic patients and much less is known about their origins and relevance in childhood. METHODS: We examined CCD with a cross-sectional approach in 1263 Italian pollen allergic children (Panallergen in Paediatrics, PAN-PED), as well as with a longitudinal approach in 612 German children (Multicenter Allergy Study, MAS), whose cutaneous and IgE sensitization profile to a broad panel of allergen extracts and molecules was already known. The presence and levels of IgE to CCD were examined in the sera of both cohorts using bromelain (MUXF3) as reagent and a novel chemiluminescence detection system, operating in a solid phase of fluorescently labelled and streptavidin-coated paramagnetic microparticles (NOVEOS, HYCOR, USA). RESULTS: IgE to CCD was found in 22% of the Italian pollen allergic children, mainly in association with an IgE response to grass pollen. Children with IgE to CCD had higher total IgE levels and were sensitized to more allergenic molecules of Phleum pratense than those with no IgE to CCD. Among participants of the German MAS birth cohort study, IgE to CCD emerged early in life (even at pre-school age), with IgE sensitization to group 1 and 4 allergen molecules of grasses, and almost invariably persisted over the full observation period. CONCLUSIONS: Our results contribute to dissect the immunological origins, onset, evolution and risk factors of CCD-sIgE response in childhood, and raise the hypothesis that group 1 and/or 4 allergen molecules of grass pollen are major inducers of these antibodies through an antigen-specific, T-B cell cognate interaction.
Subject(s)
Hypersensitivity , Immunoglobulin E , Adult , Humans , Child , Child, Preschool , Cohort Studies , Prevalence , Allergens , Carbohydrates , Risk Factors , Cross ReactionsABSTRACT
BACKGROUND: International guidelines disagree on how best to diagnose primary ciliary dyskinesia (PCD), not least because many tests rely on pattern recognition. We hypothesized that quantitative distribution of ciliary ultrastructural and motion abnormalities would detect most frequent PCD-causing groups of genes by soft computing analysis. METHODS: Archived data on transmission electron microscopy and high-speed video analysis from 212 PCD patients were re-examined to quantitate distribution of ultrastructural (10 parameters) and functional ciliary features (4 beat pattern and 2 frequency parameters). The correlation between ultrastructural and motion features was evaluated by blinded clustering analysis of the first two principal components, obtained from ultrastructural variables for each patient. Soft computing was applied to ultrastructure to predict ciliary beat frequency (CBF) and motion patterns by a regression model. Another model classified the patients into the five most frequent PCD-causing gene groups, from their ultrastructure, CBF and beat patterns. RESULTS: The patients were subdivided into six clusters with similar values to homologous ultrastructural phenotype, motion patterns, and CBF, except for clusters 1 and 4, attributable to normal ultrastructure. The regression model confirmed the ability to predict functional ciliary features from ultrastructural parameters. The genetic classification model identified most of the different groups of genes, starting from all quantitative parameters. CONCLUSIONS: Applying soft computing methodologies to PCD diagnostic tests optimizes their value by moving from pattern recognition to quantification. The approach may also be useful to evaluate atypical PCD, and novel genetic abnormalities of unclear disease-producing potential in the future.
Subject(s)
Ciliary Motility Disorders , Kartagener Syndrome , Humans , Kartagener Syndrome/diagnosis , Kartagener Syndrome/genetics , Soft Computing , Cilia/genetics , Cilia/ultrastructure , Microscopy, Video , Microscopy, Electron, Transmission , Ciliary Motility Disorders/diagnosis , Ciliary Motility Disorders/geneticsABSTRACT
The Hyper IgE Syndromes are rare primary immunodeficiencies characterized by eczema, recurrent skin and respiratory infections and elevated serum IgE levels. Nowadays a geneticmolecular characterization is possible and allows the distinction in various monogenic pathologies, which share some clinical characteristics but also important differences. In addition to long-known STAT3 and DOCK8 gene mutations, in fact, also ZNF341, CARD11, ERBB2IP, IL6R and IL6ST genes mutations can cause the disease. The main clinical manifestations are represented by newborn rash, eczema similar to atopic dermatitis, bacterial and viral skin infections, cold abscesses, respiratory infections with possible pulmonary complications, allergies, gastrointestinal manifestations, malignancies and connective tissue abnormalities. Diagnosis is still a challenge because, especially in the early stages of life, it is difficult to distinguish from other pathologies characterized by eczema and high IgE, such as atopic dermatitis. Several scores and diagnostic pathways have been developed, but it is essential to seek a genetic diagnosis. Treatment is based on prevention and early treatment of infections, meticulous skincare, intravenous immunoglobulins and HSCT, which, in some HIES subtypes, can modify the prognosis. Prognosis is related to the affected gene, but also to early diagnosis, timely treatment of infections and early HSCT.
Subject(s)
Dermatitis, Atopic , Eczema , Job Syndrome , Respiratory Tract Infections , Infant, Newborn , Humans , Job Syndrome/diagnosis , Job Syndrome/genetics , Job Syndrome/therapy , Dermatitis, Atopic/diagnosis , Mutation , Immunoglobulin E , Respiratory Tract Infections/complications , Guanine Nucleotide Exchange Factors/geneticsABSTRACT
The burden of group A streptococcus (GAS) infection and its rheumatic sequelae remains dramatically high, especially in low-income countries. Recently, an increased number of Acute Rheumatic Fever (ARF) cases was documented in many regions of Italy. The diagnosis of rheumatic sequelae relies on clinical signs and on the evaluation of the Antistreptolysin O titre (ASO), whose variations are globally reported. To re-examine the standard reference value of ASO titre, by measuring either its upper limit of normal (ULN) in a population of healthy children (HC) or comparing these values with streptococcal antibodies registered in a cohort of patients affected by the rheumatic sequelae of GAS infection. We performed a multicenter retrospective study. We enrolled 125 HC, aged 2-17 years, and a total of 181 patients affected by ARF, acute streptococcal pharyngitis, post-streptococcal arthritis, Henoch-Schönlein purpura and erythema nodosum, divided into four groups. The levels of ASO and anti-deoxyribonuclease B (anti-DNase B) titres were analyzed and compared among the various groups. Moreover, the 80th percentile value was calculated and established as the ULN for ASO titre in HC group. The ULN for ASO titre in overall HC group was 515 IU/mL, resulting in higher than used in the routine investigation. The ASO titre was significantly higher in patients with rheumatic sequelae compared with HC group, with a peak in the age between 5 and 15 years. Conclusion: Our study established a new ULN normal value of streptococcal serology in a childhood and adolescent population of Italy, suggesting the need to extend this revaluation to the critical areas, in order to avoid underestimating ARF diagnosis. The correct interpretation of ASO and anti-DNase B values in the context of rheumatic diseases has been discussed. What is Known: ⢠The global burden of disease caused by group A streptococcus is not known and remains an important cause of morbidity and mortality. Acute rheumatic fever continues to be a serious worldwide public health problem and a recent recurrence of group A streptococcus infection cases is observed. ⢠The streptococcal sequelae requires evidence of preceding streptococcal infection, commonly elevated streptococcal antibody titre, but the upper limit for these titres varies considerably based on age group, region, and origin. What is New: ⢠This study provides population-specific values for streptococcal antibody titres in Italy. ⢠Interpret the results of group A streptococcal antibody tests within the clinical context.
Subject(s)
Rheumatic Diseases , Rheumatic Fever , Streptococcal Infections , Child , Adolescent , Humans , Child, Preschool , Rheumatic Fever/diagnosis , Rheumatic Fever/epidemiology , Antistreptolysin , Retrospective Studies , Streptococcal Infections/complications , Streptococcal Infections/diagnosis , Streptococcal Infections/epidemiology , Streptococcus pyogenes , Antibodies, Bacterial , Disease ProgressionABSTRACT
Nutritional Immunity is one of the most ancient innate immune responses, during which the body can restrict nutrients availability to pathogens and restricts their uptake by the gut mucosa (mucosal block). Though this can be a beneficial strategy during infection, it also is associated with non-communicable diseases-where the pathogen is missing; leading to increased morbidity and mortality as micronutritional uptake and distribution in the body is hindered. Here, we discuss the acute immune response in respect to nutrients, the opposing nutritional demands of regulatory and inflammatory cells and particularly focus on some nutrients linked with inflammation such as iron, vitamins A, Bs, C, and other antioxidants. We propose that while the absorption of certain micronutrients is hindered during inflammation, the dietary lymph path remains available. As such, several clinical trials investigated the role of the lymphatic system during protein absorption, following a ketogenic diet and an increased intake of antioxidants, vitamins, and minerals, in reducing inflammation and ameliorating disease.
Subject(s)
Micronutrients , Vitamins , Humans , Micronutrients/therapeutic use , Vitamins/therapeutic use , Antioxidants/metabolism , Vitamin A , Inflammation/drug therapy , Mucous Membrane/metabolismABSTRACT
Disorders of sexual development (DSDs) encompass a group of congenital conditions associated with atypical development of internal and external genital structures. Among those with DSDs are 46,XX males, whose condition mainly arises due to the translocation of SRY onto an X chromosome or an autosome. In the few SRY-negative 46,XX males, overexpression of other pro-testis genes or failure of pro-ovarian/anti-testis genes may be involved, even if a non-negligible number of cases remain unexplained. A three-year-old boy with an SRY-negative 46,XX karyotype showed a normal male phenotype and normal prepubertal values for testicular hormones. A heterozygous de novo in tandem duplication of 50,221 bp, which encompassed exons 2 and 3 of the Doublesex and Mab-3-related transcription factor 1 (DMRT1) gene, was detected using MPLA, CGH-array analysis, and Sanger sequencing. Both breakpoints were in the intronic regions, and this duplication did not stop or shift the coding frame. Additional pathogenic or uncertain variants were not found in a known pro-testis/anti-ovary gene cascade using a custom NGS panel and whole genome sequencing. The duplication may have allowed DMRT1 to escape the transcriptional repression that normally occurs in 46,XX fetal gonads and thus permitted the testicular determination cascade to switch on. So far, no case of SRY-negative 46,XX DSD with alterations in DMRT1 has been described.
Subject(s)
Testis , Transcription Factors , Humans , Male , Child, Preschool , Transcription Factors/genetics , Gonads , Sexual Development/genetics , KaryotypingABSTRACT
Ataxia telangiectasia (AT) is a rare disease characterized by the early onset and slow progression of neurodegenerative defects, mainly affecting the cerebellum, associated with immunodeficiency and teleangiectasias. Ataxia is the hallmark of the disease and usually its first manifestation. Overt cerebellar ataxia usually becomes evident between 16 and 18 months of age, after the onset of walking, and is characterized by frequent falls and an ataxic gait with an enlarged base. We report the case of a child who first presented with serious recurrent infectious, without exhibiting neurological symptoms. The patient was initially diagnosed with combined immunodeficiency (CID) of unknown etiology for nearly 3 years, before he was definitively diagnosed with ataxia telangiectasia.
ABSTRACT
The ketogenic diet (KD) restricts carbohydrate consumption, leading to an increase in ketone bodies, such as acetoacetate, ß-hydroxybutyrate, and acetone, which are utilized as energy substrates. This dietary approach impacts several biochemical processes, resulting in improved clinical management of various disorders, particularly in childhood. However, the exact mechanisms underlying the efficacy of KD remain unclear. Interestingly, KD may also impact the gut microbiota, which plays a pivotal role in metabolism, nutrition, and the development of the immune and nervous systems. KD has gained popularity for its potential benefits in weight loss, blood sugar control, and certain neurological conditions. This narrative review sums up KD-related studies published over 30 years. While short-term studies have provided valuable insights into the effects of KD on the gut microbiota, persistent uncertainties surround its long-term efficacy and potential for inducing dysbiosis. The significant influence of KD on epigenetic mechanisms, intracellular pathways, and gut microbial composition underscores its potential as a therapeutic choice. However, a judicious consideration of the potential risks associated with the strict adherence to a low-carbohydrate, high-fat, and high-protein regimen over prolonged periods is imperative. As KDs gain popularity among the adolescent and young adult demographic for weight management, it becomes imperative to undertake additional research to comprehensively assess their impact on nutritional status and gut microbiota, ensuring a holistic and sustainable approach to medical nutrition.