ABSTRACT
Activated phosphoinositide 3-kinase (PI3Kδ) Syndrome (APDS) is an inborn error of immunity (IEI) with a variable clinical presentation, characterized by infection susceptibility and immune dysregulation that may overlaps with other Primary Immune Regulatory Disorders (PIRDs). The rarity of the disease, its recent discovery, and the multiform /multifaced clinical presentation make it difficult to establish a correct diagnosis, especially at an early stage. As a result, the true prevalence of the pathology remains unknown. There is no treatment protocol for APDS, and drug therapy is primarily focused on treating symptoms. The most common therapies include immunoglobulin replacement therapy, antimicrobial prophylaxis, and immunosuppressive drugs. Hematopoietic stem cell transplantation (HSCT) has been used in some cases, but the risk-benefit balance remains unclear. With the upcoming introduction of specific medications, such as selective inhibitors for PI3Kδ, clinicians are shifting their attention towards target therapy.This review provides a comprehensive overview of APDS with a focus on diagnostic and treatments procedures available. This review may be useful in implementing strategies for a more efficient patients' management and therapeutic interventions.Main Text.
Subject(s)
Class I Phosphatidylinositol 3-Kinases , Primary Immunodeficiency Diseases , Humans , Primary Immunodeficiency Diseases/diagnosis , Primary Immunodeficiency Diseases/therapy , Italy , Hematopoietic Stem Cell TransplantationABSTRACT
Kabuki Syndrome (KS) is a multisystemic genetic disorder. A portion of patients has immunological manifestations characterized by increased susceptibility to infections and autoimmunity. Aiming to describe the clinical and laboratory immunological aspects of KS, we conducted a retrospective multicenter observational study on patients with KS treated in centers affiliated to the Italian Primary Immunodeficiency Network.Thirty-nine patients were enrolled, with a median age at evaluation of 10 years (range: 3 m-21y). All individuals had organ malformations of variable severity. Congenital heart defect (CHD) was present in 19/39 patients (49%) and required surgical correction in 9/39 (23%), with associated thymectomy in 7/39 (18%). Autoimmune cytopenia occurred in 6/39 patients (15%) and was significantly correlated with thymectomy (p < 0.002), but not CHD. Individuals with cytopenia treated with mycophenolate as long-term immunomodulatory treatment (n = 4) showed complete response. Increased susceptibility to infections was observed in 22/32 patients (69%). IgG, IgA, and IgM were low in 13/29 (45%), 13/30 (43%) and 4/29 (14%) patients, respectively. Immunoglobulin substitution was required in three patients. Lymphocyte subsets were normal in all patients except for reduced naïve T-cells in 3/15 patients (20%) and reduced memory switched B-cells in 3/17 patients (18%). Elevated CD3 + TCRαß + CD4-CD8-T-cells were present in 5/17 individuals (23%) and were correlated with hematological and overall autoimmunity (p < 0.05).In conclusion, immunological manifestations of KS in our cohort include susceptibility to infections, antibody deficiency, and autoimmunity. Autoimmune cytopenia is correlated with thymectomy and elevated CD3 + TCRαß + CD4-CD8-T-cells, and benefits from treatment with mycophenolate.
Subject(s)
Abnormalities, Multiple , Face/abnormalities , Hematologic Diseases , Vestibular Diseases , Humans , Female , Retrospective Studies , Male , Child , Hematologic Diseases/immunology , Hematologic Diseases/therapy , Adolescent , Italy , Vestibular Diseases/immunology , Child, Preschool , Young Adult , Abnormalities, Multiple/immunology , Infant , Autoimmunity , AdultABSTRACT
Background: Activated phosphoinositide 3-kinase-δ syndrome 2 (APDS2) is characterized by lymphoproliferation and increased risk of malignancy. FDG-PET/CT may represent a helpful diagnostic tool for differentiating these clinical features and correctly diagnosing inborn errors of immunity (IEI). Case report: We present the case of a female patient diagnosed with Hodgkin's lymphoma at 19 years of age, although atypical imaging aspects emerged: baseline FDG-PET/CT revealed several hot lymph nodes with a symmetrical distribution, and increased tracer uptake in spleen, axial, and appendicular bone marrow. Imaging repeated after chemotherapy and autologous stem cell transplantation showed persistent increased FDG uptake at multiple supradiaphragmatic nodes and in bone marrow. After the diagnosis of APDS2 and rapamycin treatment, FDG-PET/CT confirmed complete metabolic normalization of all sites. Conclusions: In the IEI scenario, FDG-PET/CT plays an effective role in differentiating malignant proliferation and immune dysregulation phenotypes. Atypical patterns at FDG-PET/CT should be interpreted as a red flag for the need of an early immunological evaluation.
ABSTRACT
In this work, phytochemical analysis on different extracts of Roccella tinctoria DC. was reported using different techniques with respect to the past. Twenty volatile and three non-volatile compounds were identified, some of which were found in this species for the first time. The methanolic extracts and their non-volatile components were then evaluated for their antitumor effects in cancerous A549 and Mz-ChA-1 cells and for their tolerability in non-cancerous BEAS-2B and H69 cells, showing IC50 values from 94.6 µg/mL to 416.4 µg/mL, in general. The same extracts and compounds were also tested for their antifungal effects in Candida albicans, with only compound 2 being active, with an MIC50 value of 87 µg/mL. In addition, they were tested for their anti-Candida adhesion activity, anti-Candida biofilm formation, and anti-Candida mature biofilm inhibition, with efficacy percentages generally above 50% but not for all of them. Lastly, the DF3 extract and compounds 1-2 were tested in vivo according to the Galleria mellonella survival assay, showing positive mortality rates above 50% at different concentrations. All these biological assays were conducted on this species for the first time. Comparisons with other lichens and compounds were also presented and discussed.
ABSTRACT
We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-α2 in 10 patients: IFN-α2 only in three, IFN-α2 plus IFN-ω in five, and IFN-α2, IFN-ω plus IFN-ß in two; IFN-ω only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-α2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-ω in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-α2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-ω only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-ω and/or IFN-α2.
Subject(s)
COVID-19 , Interferon Type I , Child , Humans , Interferon-alpha , AutoantibodiesABSTRACT
GATA2 deficiency is a rare disorder encompassing a broadly variable phenotype and its clinical picture is continuously evolving. Since it was first described in 2011, up to 500 patients have been reported. Here, we describe a cohort of 31 Italian patients (26 families) with molecular diagnosis of GATA2 deficiency. Patients were recruited contacting all the Italian Association of Pediatric Hematology and Oncology (AIEOP) centers, the Hematology Department in their institution and Italian societies involved in the field of vascular anomalies, otorhinolaryngology, dermatology, infectious and respiratory diseases. Median age at the time of first manifestation, molecular diagnosis and last follow-up visit was 12.5 (age-range, 2-52 years), 18 (age-range, 7-64 years) and 22 years (age-range, 3-64), respectively. Infections (39%), hematological malignancies (23%) and undefined cytopenia (16%) were the most frequent symptoms at the onset of the disease. The majority of patients (55%) underwent hematopoietic stem cell transplantation. During the follow-up rarer manifestations emerged. The clinical penetrance was highly variable, with the coexistence of severely affected pediatric patients and asymptomatic adults in the same pedigree. Two individuals remained asymptomatic at the last follow-up visit. Our study highlights new (pilonidal cyst/sacrococcygeal fistula, cholangiocarcinoma and gastric adenocarcinoma) phenotypes and show that lymphedema may be associated with null/regulatory mutations. Countrywide studies providing long prospective follow-up are essential to unveil the exact burden of rarer manifestations and the natural history in GATA2 deficiency.
Subject(s)
GATA2 Deficiency , Hematopoietic Stem Cell Transplantation , Adolescent , Adult , Child , Child, Preschool , Humans , Middle Aged , Young Adult , GATA2 Deficiency/diagnosis , GATA2 Deficiency/genetics , GATA2 Deficiency/therapy , Genetic Association Studies , Italy/epidemiology , Prospective StudiesABSTRACT
BACKGROUND: The large-scale utilization of immunoglobulins in patients with inborn errors of immunity (IEIs) since 1952 prompted the discovery of their key role at high doses as immunomodulatory and anti-inflammatory therapy, in the treatment of IEI-related immune dysregulation disorders, according to labelled and off-label indications. Recent years have been dominated by a progressive imbalance between the gradual but constant increase in the use of immunoglobulins and their availability, exacerbated by the SARS-CoV-2 pandemic. OBJECTIVES: To provide pragmatic indications for a need-based application of high-dose immunoglobulins in the pediatric context. SOURCES: A literature search was performed using PubMed, from inception until 1st August 2023, including the following keywords: anti-inflammatory; children; high dose gammaglobulin; high dose immunoglobulin; immune dysregulation; immunomodulation; immunomodulatory; inflammation; intravenous gammaglobulin; intravenous immunoglobulin; off-label; pediatric; subcutaneous gammaglobulin; subcutaneous immunoglobulin. All article types were considered. IMPLICATIONS: In the light of the current imbalance between gammaglobulins' demand and availability, this review advocates the urgency of a more conscious utilization of this medical product, giving indications about benefits, risks, cost-effectiveness, and administration routes of high-dose immunoglobulins in children with hematologic, neurologic, and inflammatory immune dysregulation disorders, prompting further research towards a responsible employment of gammaglobulins and improving the therapeutical decisional process.
Subject(s)
Immunoglobulins, Intravenous , Off-Label Use , Humans , Child , Immunoglobulins, Intravenous/therapeutic use , Anti-Inflammatory Agents/therapeutic use , SARS-CoV-2 , ImmunomodulationABSTRACT
During the first years of the HIV pandemic, the virus diffusion was responsible for discriminatory behavior from medical and dental care workers towards HIV-infected patients, as described by our research group in 2009. The aim of the current study was to provide an update on the previous data, investigating the presence of discriminatory behaviors, evaluating the level of dentists' knowledge about the virus and proposing strategies to be implemented to avoid professional exposure and cross-infections. This study was a cross-sectional, online, national survey on dentists, members of the main national dental associations (ANDI and AIO). The questionnaire was divided into four major sections, with the same structure as the questionnaire administered in 2009. The differences between groups were analyzed using the software program IBM SPSS Statistic, version 21.0. A total of 1054 dentists filled out the questionnaire completely. Among them 0.04% revealed a discriminatory attitude towards HIV-infected patients. The univariate analysis showed that discrimination towards HIV + patients was statistically associated with personal experiences and the level of fear associated with treating them (p = 0.001) and with the type of dental treatments performed (p = 0.01). This cross-sectional study revealed the persistence of dentists who still discriminate against HIV + patients, and the percentage of these dentists was only slightly lower than that in the previous survey (4.3% in the present survey vs. 4.5%). The survey also depicted other information worthy of consideration, such as a perceived ability to detect HIV + patients based on their appearance, complaints about not having received adequate training for treating HIV + individuals, and a lack of scientific knowledge about the virus. From the evidence reported by the present survey, it can be argued that universities, professional boards, and training institutions must increase their efforts in spreading correct knowledge about HIV among all dental care workers.
ABSTRACT
Multisystem inflammatory syndrome (MIS-C) is a rare condition associated with COVID-19 affecting children, characterized by severe and aberrant systemic inflammation leading to nonspecific symptoms, such as gastrointestinal, cardiac, respiratory, hematological, and neurological disorders. In the last year, we have experienced a progressive reduction in the incidence and severity of MIS-C, reflecting the worldwide trend. Thus, starting from the overall trend in the disease in different continents, we reviewed the literature, hypothesizing the potential influencing factors contributing to the reduction in cases and the severity of MIS-C, particularly the vaccination campaign, the spread of different SARS-CoV-2 variants (VOCs), and the changes in human immunological response. The decrease in the severity of MIS-C and its incidence seem to be related to a combination of different factors rather than a single cause. Maturation of an immunological memory to SARS-CoV-2 over time, the implication of mutations of key amino acids of S protein in VOCs, and the overall immune response elicited by vaccination over the loss of neutralization of vaccines to VOCs seem to play an important role in this change.
ABSTRACT
Kabuki syndrome (KS) is a rare multisystemic disease due to mutations in the KMT2D or KDM6A genes, which act as epigenetic modulators of different processes, including immune response. The syndrome is characterized by anomalies in multiple organ systems, and it is associated with autoimmune and inflammatory disorders, and an underlying immunological phenotype characterized by immunodeficiency and immune dysregulation. Up to 17% of KS patients present with immune thrombocytopenia characterized by a severe, chronic or relapsing course, and often associated to other hematological autoimmune diseases including autoimmune hemolytic anemia, eventually resulting in Evans syndrome (ES). A 23-year-old woman, clinically diagnosed with KS and presenting from the age of 3 years with ES was referred to the Rare Diseases Centre of our Pediatric Department for corticosteroid-induced hyperglycemia. Several ES relapses and recurrent respiratory infections in the previous years were reported. Severe hypogammaglobulinemia, splenomegaly and signs of chronic lung inflammation were diagnosed only at the time of our observation. Supportive treatment with amoxicillin-clavulanate prophylaxis and recombinant human hyaluronidase-facilitated subcutaneous immunoglobulin replacement were immediately started. In KS patients, the failure of B-cell development and the lack of autoreactive immune cells suppression can lead to immunodeficiency and autoimmunity that may be undiagnosed for a long time. Our patient's case is paradigmatic since she presented with preventable morbidity and severe lung disease years after disease onset. This case emphasizes the importance of suspecting immune dysregulation in KS. Pathogenesis and immunological complications of KS are discussed. Moreover, the need to perform immunologic evaluations is highlighted both at the time of KS diagnosis and during disease follow-up, in order to allow proper treatment while intercepting avoidable morbidity in these patients.
ABSTRACT
Mosquito-borne West Nile virus (WNV) infection is benign in most individuals but can cause encephalitis in <1% of infected individuals. We show that â¼35% of patients hospitalized for WNV disease (WNVD) in six independent cohorts from the EU and USA carry auto-Abs neutralizing IFN-α and/or -ω. The prevalence of these antibodies is highest in patients with encephalitis (â¼40%), and that in individuals with silent WNV infection is as low as that in the general population. The odds ratios for WNVD in individuals with these auto-Abs relative to those without them in the general population range from 19.0 (95% CI 15.0-24.0, P value <10-15) for auto-Abs neutralizing only 100 pg/ml IFN-α and/or IFN-ω to 127.4 (CI 87.1-186.4, P value <10-15) for auto-Abs neutralizing both IFN-α and IFN-ω at a concentration of 10 ng/ml. These antibodies block the protective effect of IFN-α in Vero cells infected with WNV in vitro. Auto-Abs neutralizing IFN-α and/or IFN-ω underlie â¼40% of cases of WNV encephalitis.
Subject(s)
Interferon Type I , West Nile Fever , West Nile virus , Animals , Chlorocebus aethiops , Humans , Vero Cells , Autoantibodies , Antibodies, Viral , Interferon-alphaABSTRACT
Job's syndrome, or autosomal dominant hyperimmunoglobulin E syndrome (AD-HIES, STAT3-Dominant Negative), is a rare inborn error of immunity (IEI) with multi-organ involvement and long-life post-infective damage. Longitudinal registries are of primary importance in improving our knowledge of the natural history and management of these rare disorders. This study aimed to describe the natural history of 30 Italian patients with AD-HIES recorded in the Italian network for primary immunodeficiency (IPINet) registry. This study shows the incidence of manifestations present at the time of diagnosis versus those that arose during follow up at a referral center for IEI. The mean time of diagnostic delay was 13.7 years, while the age of disease onset was < 12 months in 66.7% of patients. Respiratory complications, namely bronchiectasis and pneumatoceles, were present at diagnosis in 46.7% and 43.3% of patients, respectively. Antimicrobial prophylaxis resulted in a decrease in the incidence of pneumonia from 76.7% to 46.7%. At the time of diagnosis, skin involvement was present in 93.3% of the patients, including eczema (80.8%) and abscesses (66.7%). At the time of follow-up, under therapy, the prevalence of complications decreased: eczema and skin abscesses reduced to 63.3% and 56.7%, respectively. Antifungal prophylaxis decreased the incidence of mucocutaneous candidiasis from 70% to 56.7%. During the SARS-CoV-2 pandemic, seven patients developed COVID-19. Survival analyses showed that 27 out of 30 patients survived, while three patients died at ages of 28, 39, and 46 years as a consequence of lung bleeding, lymphoma, and sepsis, respectively. Analysis of a cumulative follow-up period of 278.7 patient-years showed that early diagnosis, adequate management at expertise centers for IEI, prophylactic antibiotics, and antifungal therapy improve outcomes and can positively influence the life expectancy of patients.
ABSTRACT
Febrile infection-related epilepsy syndrome (FIRES) is a prolonged refractory status epilepticus (SE) that develops among healthy individuals after a febrile infection. FIRES treatment is challenging due to its poor response to antiseizure medications (ASMs) and anesthetic drugs. The use of cannabidiol (CBD) as an adjunctive treatment has been suggested, albeit data about its role in the acute phase is lacking. This report describes the use of purified CBD in the acute phase of two pediatric cases of FIRES and their long-term outcome. Both children were treated with several ASMs, immunomodulators, anesthetics, and nonpharmacological treatment (ketogenic diet). CBD was administered, as an adjunctive treatment, through nasogastric tube about 30 days after onset. SE resolved within 3 days of reaching the target dose and both were seizure-free for 1 year after. Although it is difficult to define the extent to which each previous therapy contributed to recovery, in both cases CBD therapy was a turning point, reinforcing its potential role as add-on treatment in the acute phase of FIRES.
Subject(s)
Anesthetics , Cannabidiol , Drug Resistant Epilepsy , Encephalitis , Epileptic Syndromes , Status Epilepticus , Child , Humans , Cannabidiol/therapeutic use , Seizures/drug therapy , Status Epilepticus/drug therapy , Drug Resistant Epilepsy/drug therapy , Anesthetics/therapeutic use , Epileptic Syndromes/drug therapyABSTRACT
INTRODUCTION: According to the recent adaptation of the I-PACE model, desire thinking and craving might be closely related to problematic Internet pornography use. The overall aim of the present study was to investigate the role of two components of desire thinking (imaginal prefiguration and verbal perseveration) and craving in problematic Internet pornography use. Furthermore, we examined gender differences in the underlying mechanism linking desire thinking to problematic Internet pornography use. METHOD: A total of 414 Italian adults (mean age = 27.55 years, SD = 6.13; age range = 18-58; 53.6 % men) participated in this study. Participants completed an online survey to assess problematic Internet pornography use, pornography craving, desire thinking and problematic Internet use. Path analyses and a multi-group approach were used to test the relationships among variables and to explore gender differences. RESULTS: Imaginal prefiguration was associated to pornography craving which, in turn, was associated to verbal perseveration as proximal antecedent of problematic Internet pornography use, above and beyond the effect of age, relationship status, and problematic Internet use. Two paths significantly differed between men and women: the path between verbal perseveration and problematic Internet pornography, which for women was weaker and did not reach significance; and the path between problematic Internet use and problematic Internet pornography use that was not significant for women. CONCLUSIONS: In line with the I-PACE model, the present study provided support for the potential role of desire thinking in problematic Internet pornography use as a specific Internet-use disorder and expanded the literature in the field by testing unexplored gender differences. Preventive and clinical implications are discussed.
Subject(s)
Craving , Erotica , Adolescent , Adult , Female , Humans , Internet , Internet Use , Male , Middle Aged , Surveys and Questionnaires , Thinking , Young AdultABSTRACT
BACKGROUND: CBL syndrome is a RASopathy caused by heterozygous germline mutations of the Casitas B-lineage lymphoma (CBL) gene. It is characterized by heterogeneous clinical phenotype, including developmental delay, facial dysmorphisms, cardiovascular malformations and an increased risk of cancer development, particularly juvenile myelomonocytic leukemia (JMML). Although the clinical phenotype has been progressively defined in recent years, immunological manifestations have not been well elucidated to date. METHODS: We studied the genetic, immunological, coagulative, and clinical profile of a family with CBL syndrome that came to our observation after the diagnosis of JMML, with homozygous CBL mutation, in one of the members. RESULTS: Variant analysis revealed the co-occurrence of CBL heterozygous mutation (c.1141 T > C) and SH2B3 mutation (c.1697G > A) in two other members. Patients carrying both mutations showed an ALPS-like phenotype characterized by lymphoproliferation, cytopenia, increased double-negative T-cells, impaired Fas-mediated lymphocyte apoptosis, altered cell death in PBMC and low TRECs expression. A coagulative work-up was also performed and showed the presence of subclinical coagulative alterations in patients carrying both mutations. CONCLUSION: In the reported family, we described immune dysregulation, as part of the clinical spectrum of CBL mutation with the co-occurrence of SH2B3.
Subject(s)
Leukemia, Myelomonocytic, Juvenile , Proto-Oncogene Proteins c-cbl , Germ Cells/metabolism , Germ-Line Mutation/genetics , Humans , Leukemia, Myelomonocytic, Juvenile/complications , Leukemia, Myelomonocytic, Juvenile/genetics , Leukocytes, Mononuclear/metabolism , Proto-Oncogene Proteins c-cbl/genetics , Proto-Oncogene Proteins c-cbl/metabolismABSTRACT
BACKGROUND: Inborn errors of intrinsic and innate immunity constitute the focus of a growing research field that investigates the molecular mechanisms underlying susceptibility to infections previously not considered part of the spectrum of inborn errors of immunity. These so-called nonconventional inborn errors of immunity often occur as infections caused by a narrow spectrum of microorganisms in otherwise healthy subjects. OBJECTIVES: This review aimed to provide a framework for identifying and evaluating patients with viral, bacterial, mycobacterial, and fungal infection needing further assessment for inborn errors of intrinsic and innate immunity. SOURCES: A literature search was performed using PubMed, from inception until 1 May 2022. The search included the following keywords: "inborn errors of immunity"; "inborn errors of innate immunity"; "primary immune deficiency"; "primary immunodeficiency"; "infections"; "infectious susceptibility"; "virus"; "pyogenic bacteria"; "mycobacteria"; "fungi". All article types were considered. CONTENT: We review the definition of what can be considered an inborn error of immunity and how the definition changed over the last â¼25 years. We further provide criteria to rule out secondary immunodeficiencies, identify patients needing further clinical and laboratory immunological assessment, and suspect and diagnose an inborn error of intrinsic and innate immunity. These steps are proposed as part of an algorithm. IMPLICATIONS: Patients with unexplained life-threatening infections, including otherwise healthy subjects, should be systematically screened for known inborn errors of immunity. The early diagnosis can prevent recurrence of life-threatening infections in the patients and reduce the total burden of infectious diseases.
Subject(s)
Communicable Diseases , Immunologic Deficiency Syndromes , Mycobacterium Infections , Mycoses , Humans , Immunity, Innate , Immunologic Deficiency Syndromes/complications , Mycobacterium Infections/diagnosis , Communicable Diseases/complications , BacteriaABSTRACT
Sickle cell disease (SCD) is a condition of functional hypo-/a-splenism in which predisposition to bacterial infections is only a facet of a wide spectrum of immune-dysregulation disorders forming the clinical expression of a peculiar immunophenotype. The objective of this study was to perform an in-depth immunophenotypical characterization of SCD pediatric patients, looking for plausible correlations between immunological biomarkers, the impact of hydroxyurea (HU) treatment and clinical course. This was an observational case−control study including 43 patients. The cohort was divided into two main groups, SCD subjects (19/43) and controls (24/43), differing in the presence/absence of an SCD diagnosis. The SCD group was split up into HU+ (12/19) and HU− (7/19) subgroups, respectively receiving or not a concomitant HU treatment. The principal outcomes measured were differences in the immunophenotyping between SCD patients and controls through chi-squared tests, t-tests, and Pearson's correlation analysis between clinical and immunological parameters. Leukocyte and neutrophil increase, T-cell depletion with prevalence of memory T-cell compartment, NK and B-naïve subset elevation with memory and CD21low B subset reduction, and IgG expansion, significantly distinguished the SCD HU− subgroup from controls, with naïve T cells, switched-memory B cells and IgG maintaining differences between the SCD HU+ group and controls (p-value of <0.05). The mean CD4+ central-memory T-cell% count was the single independent variable showing a positive correlation with vaso-occlusive crisis score in the SCD group (Pearson's R = 0.039). We report preliminary data assessing plausible clinical implications of baseline and HU-related SCD immunophenotypical alterations, which need to be validated in larger samples, but potentially affecting hypo-/a-splenism immuno-chemoprophylactic recommendations.
ABSTRACT
The medaka, Oryzias latipes, is rapidly growing in importance as a model in behavioural research. However, our knowledge of its behaviour is still incomplete. In this study, we analysed the performance of medaka in 3 tests for anxiety-like behaviour (open-field test, scototaxis test, and diving test) and in 3 sociability tests (shoaling test with live stimuli, octagonal mirror test, and a modified shoaling test with mirror stimulus). The behavioural response of medaka was qualitatively similar to that observed in other teleosts in the open-field test (thigmotaxis), and in 2 sociability tests, the shoaling test and in the octagonal mirror test (attraction towards the social stimulus). In the remaining tests, medaka did not show typical anxiety (i.e., avoidance of light environments and preference for swimming at the bottom of the aquarium) and social responses (attraction towards the social stimulus). As a reference, we compared the behaviour of the medaka to that of a teleost species with well-studied behaviour, the zebrafish, tested under the same conditions. This interspecies comparison indicates several quantitative and qualitative differences across all tests, providing further evidence that the medaka responds differently to the experimental settings compared to other fish models.
Subject(s)
Oryzias , Animals , Anxiety , Anxiety Disorders , Social Behavior , ZebrafishABSTRACT
BACKGROUND: Pyogenic bacteria are associated with a wide range of clinical manifestations, ranging from common and relatively mild respiratory and cutaneous infections to life-threatening localized or systemic infections, such as sepsis and profound abscesses. Despite vaccination and the widespread use of effective antibiotic treatment, severe infection is still observed in a subset of affected patients. OBJECTIVES: We aim to summarize the available data regarding inborn errors of immunity that result in a high risk of severe pyogenic infections. SOURCES: Case series, as well as review and original articles on human genetic susceptibility to pyogenic infections were examined. CONTENT: We review host-associated factors resulting in inborn errors of immunity and leading to a susceptibility to pyogenic infections, including deficiency in major components of the immune system (e.g., neutrophils, complement, immunoglobulin, and spleen function) and novel monogenic disorders resulting in specific susceptibility to pyogenic infection. Specifically, innate immune system deficiency involving toll-like receptors and associated signaling typically predispose to a narrow spectrum of bacterial diseases in otherwise healthy people, making a diagnosis more difficult to suspect and confirm. More complex syndromes, such as hyper IgE syndrome, are associated with a high risk of pyogenic infections due to an impairment of the interleukin-6 or -17 signaling, demonstrating the pivotal role of these pathways in controlling bacterial infections. IMPLICATIONS: In clinical practice, awareness of such conditions is essential, especially in the pediatric setting, to avoid a potentially fatal diagnostic delay, set the most proper and prompt treatment, and ensure prevention of severe complications.