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Allergy, Asthma, and Clinical... Aug 2023Inborn errors of immunity (IEIs) are considered significant challenges for children with IEIs, their families, and their medical providers. Infections are the most...
BACKGROUND
Inborn errors of immunity (IEIs) are considered significant challenges for children with IEIs, their families, and their medical providers. Infections are the most common complication of IEIs and children can acquire coronavirus disease 2019 (COVID-19) even when protective measures are taken.
OBJECTIVES
To estimate the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children with IEIs and analyse the demographic parameters, clinical characteristics and treatment outcomes in children with IEIs with COVID-19 illness.
METHODS
For this systematic review, we searched ProQuest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guideline for studies on the development of COVID-19 in children with IEIs, published from December 1, 2019 to February 28, 2023, with English language restriction.
RESULTS
Of the 1095 papers that were identified, 116 articles were included in the systematic review (73 case report, 38 cohort 4 case-series and 1 case-control studies). Studies involving 710 children with IEIs with confirmed COVID-19 were analyzed. Among all 710 IEIs pediatric cases who acquired SARS-CoV-2, some children were documented to be admitted to the intensive care unit (ICU) (n = 119, 16.8%), intubated and placed on mechanical ventilation (n = 87, 12.2%), suffered acute respiratory distress syndrome (n = 98, 13.8%) or died (n = 60, 8.4%). Overall, COVID-19 in children with different IEIs patents resulted in no or low severity of disease in more than 76% of all included cases (COVID-19 severity: asymptomatic = 105, mild = 351, or moderate = 88). The majority of children with IEIs received treatment for COVID-19 (n = 579, 81.5%). Multisystem inflammatory syndrome in children (MIS-C) due to COVID-19 in children with IEIs occurred in 103 (14.5%). Fatality in children with IEIs with COVID-19 was reported in any of the included IEIs categories for cellular and humoral immunodeficiencies (n = 19, 18.6%), immune dysregulatory diseases (n = 17, 17.9%), innate immunodeficiencies (n = 5, 10%), bone marrow failure (n = 1, 14.3%), complement deficiencies (n = 1, 9.1%), combined immunodeficiencies with associated or syndromic features (n = 7, 5.5%), phagocytic diseases (n = 3, 5.5%), autoinflammatory diseases (n = 2, 3%) and predominantly antibody deficiencies (n = 5, 2.5%). Mortality was COVID-19-related in a considerable number of children with IEIs (29/60, 48.3%). The highest ICU admission and fatality rates were observed in cases belonging to cellular and humoral immunodeficiencies (26.5% and 18.6%) and immune dysregulatory diseases (35.8% and 17.9%) groups, especially in children infected with SARS-CoV-2 who suffered severe combined immunodeficiency (28.6% and 23.8%), combined immunodeficiency (25% and 15%), familial hemophagocytic lymphohistiocytosis (40% and 20%), X-linked lymphoproliferative diseases-1 (75% and 75%) and X-linked lymphoproliferative diseases-2 (50% and 50%) compared to the other IEIs cases.
CONCLUSION
Children with IEIs infected with SARS-CoV-2 may experience higher rates of ICU admission and mortality in comparison with the immunocompetent pediatric populations. Underlying immune defects does seem to be independent risk factors for severe SARS-CoV-2 infection in children with IEIs, a number of children with SCID and CID were reported to have prolonged infections-though the number of patients is small-but especially immune dysregulation diseases (XLP1 and XLP2) and innate immunodeficiencies impairing type I interferon signalling (IFNAR1, IFNAR2 and TBK1).
PubMed: 37559153
DOI: 10.1186/s13223-023-00831-1 -
Frontiers in Immunology 2023The activation of the pyrin inflammasome represents a highly intriguing mechanism employed by the innate immune system to effectively counteract pathogenic agents.... (Review)
Review
The activation of the pyrin inflammasome represents a highly intriguing mechanism employed by the innate immune system to effectively counteract pathogenic agents. Despite its key role in innate immunity, pyrin has also garnered significant attention due to its association with a range of autoinflammatory diseases (AIDs) including familial Mediterranean fever caused by disruption of the gene, or in other genes involved in its complex regulation mechanisms. Pyrin activation is strictly dependent on homeostasis-altering molecular processes, mostly consisting of the disruption of the small Ras Homolog Family Member A (RhoA) GTPases by pathogen toxins. The downstream pathways are regulated by the phosphorylation of specific pyrin residues by the kinases PKN1/2 and the binding of the chaperone 14-3-3. Furthermore, a key role in pyrin activation is played by the cytoskeleton and gasdermin D, which is responsible for membrane pores in the context of pyroptosis. In addition, recent evidence has highlighted the role of steroid hormone catabolites and alarmins S100A8/A9 and S100A12 in pyrin-dependent inflammation. The aim of this article is to offer a comprehensive overview of the most recent evidence on the pyrin inflammasome and its molecular pathways to better understand the pathogenesis behind the significant group of pyrin-related AIDs.
Topics: Child; Humans; Familial Mediterranean Fever; Immunity, Innate; Inflammasomes; Pyrin; Inflammation; Autoimmune Diseases
PubMed: 38250061
DOI: 10.3389/fimmu.2023.1341680 -
The Journal of Clinical Investigation Mar 2024CD4+ T cells survey and maintain immune homeostasis in the brain, yet their differentiation states and functional capabilities remain unclear. Our approach, combining...
CD4+ T cells survey and maintain immune homeostasis in the brain, yet their differentiation states and functional capabilities remain unclear. Our approach, combining single-cell transcriptomic analysis, ATAC-Seq, spatial transcriptomics, and flow cytometry, revealed a distinct subset of CCR7+ CD4+ T cells resembling lymph node central memory (TCM) cells. We observed chromatin accessibility at the CCR7, CD28, and BCL-6 loci, defining molecular features of TCM. Brain CCR7+ CD4+ T cells exhibited recall proliferation and interleukin-2 production ex vivo, showcasing their functional competence. We identified the skull bone marrow as a local niche for these cells alongside CNS border tissues. Sequestering TCM cells in lymph nodes using FTY720 led to reduced CCR7+ CD4+ T cell frequencies in the cerebrospinal fluid, accompanied by increased monocyte levels and soluble markers indicating immune activation. In macaques chronically infected with SIVCL757 and experiencing viral rebound due to cessation of antiretroviral therapy, a decrease in brain CCR7+ CD4+ T cells was observed, along with increased microglial activation and initiation of neurodegenerative pathways. Our findings highlight a role for CCR7+ CD4+ T cells in CNS immune surveillance, and their decline during chronic SIV highlights their responsiveness to neuroinflammation.
Topics: Animals; Macaca mulatta; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus; CD4-Positive T-Lymphocytes; Receptors, CCR7; Brain; Neuroinflammatory Diseases; Immunologic Surveillance
PubMed: 38470479
DOI: 10.1172/JCI175332 -
British Journal of Pain Oct 2022Studies in pediatric oncology have shown that hypnosis effectively reduces patients' pain and distress during painful procedures. This remains underutilized in the...
INTRODUCTION
Studies in pediatric oncology have shown that hypnosis effectively reduces patients' pain and distress during painful procedures. This remains underutilized in the healthcare system due to the staff cost and availability of hypnotherapists. To develop the use of hypnosis-derived communication, we aimed to train nurses to use hypnosis-derived communication while they perform painful procedures.
OBJECTIVES
This study aimed to (1) develop a brief training in hypnosis-derived communication for pediatric nurses named , (2) pretest the training with experienced pediatric oncology nurses, and (3) refine the training based on nurses' suggestions.
METHODS
The training consists of two 4-h sessions: one related to relational aspects and another one presenting one of two selected hypnotic communication techniques ("pleasant place" or "magic glove"). makes use of manuals, cue card reminders, visual aids, videos, and an e-learning platform. To refine , a complete training cycle was conducted with seven female pediatric oncology nurses. A mixed method study with an evaluation questionnaire and a post-training focus group interview was conducted.
RESULTS
Quantitative data showed that nurses overall positively rated the training program: relevance and acceptability (median average of 5.4/6); use of hypnotic communication (median average of 5.2/6); expected effects (median average of 5.4/6); program implementation (5.6/6). Two general themes emerged from the qualitative data: perceptions of hypnotic communication and the evaluation of the training program. Based on nurses' suggestions, was refined by adding more practical components, more time for practice, more time between the two sessions and additional tools (cue card reminders, keywords, virtual e-learning recap module).
CONCLUSION AND CLINICAL IMPLICATIONS
The use of hypnosis-derived communication during painful procedures and the training were viewed favorably amongst pediatric nurses. offers a complete training in hypnosis-derived communication for pediatric nurses. This training fosters the optimal use of hypnosis-derived communication during care and may significantly reduce children's procedural pain and distress.
PubMed: 36389009
DOI: 10.1177/20494637221103170 -
Global Health, Science and Practice Apr 2022Despite remarkable progress in controlling HIV and TB, Uganda is one of the 30 high-burden TB/HIV countries. Approximately 53,000 Ugandans had a new HIV diagnosis in...
Despite remarkable progress in controlling HIV and TB, Uganda is one of the 30 high-burden TB/HIV countries. Approximately 53,000 Ugandans had a new HIV diagnosis in 2019, and approximately 88,000 Ugandans had a TB diagnosis in 2020. Fellows in the Uganda Public Health Fellowship Program (UPHFP) work directly with the Ministry of Health AIDS and TB Control Programs, the U.S. Centers for Disease Control and Prevention, UPHFP supervisors, and implementing partners to investigate and evaluate HIV-related and TB-related issues. These activities have contributed to the Uganda HIV and TB programs. UPHFP fellows complete projects in 7 competency domains, including outbreak investigations, surveillance evaluations, and data quality improvement. Priority HIV/AIDS/TB information gaps/topics are identified in consultation with key stakeholders, and fellows complete projects to guide program improvements and policy decisions. During 2015-2020, UPHFP fellows implemented 127 HIV and TB projects covering key program areas in AIDS and TB control programs, including care and treatment (16 projects), TB/HIV (18), prevention of mother-to-child HIV transmission (24), key and priority populations (9), pre-exposure and post-exposure prophylaxis (7), adolescent girls and young women (6), service delivery (13), and diagnosis of TB including drug-resistant TB and TB in high-risk groups (32). These projects have helped improve retention, quality of care, and treatment outcomes for people living with HIV, HIV and TB coinfected patients, and TB patients. They have also contributed to the decrease in pediatric TB and infant HIV positivity rates and improved service delivery for key populations. UPHFP results were disseminated to relevant stakeholders such as government departments, implementing partners, districts, and the general community and guided decision making. UPHFP has significantly improved HIV and TB control in Uganda. Other countries with similar programs could benefit from this approach and utilize program fellows to support HIV and TB control.
Topics: Acquired Immunodeficiency Syndrome; Adolescent; Child; Fellowships and Scholarships; Female; HIV Infections; Humans; Infectious Disease Transmission, Vertical; Public Health; Uganda
PubMed: 35487554
DOI: 10.9745/GHSP-D-21-00574 -
Frontiers in Immunology 2021During the last decade, remarkable progress with massive sequencing has been made in the identification of disease-associated genes for AIDs using next-generation...
BACKGROUND
During the last decade, remarkable progress with massive sequencing has been made in the identification of disease-associated genes for AIDs using next-generation sequencing technologies (NGS). An international group of experts described the ideal genetic screening method which should give information about SNVs, InDels, Copy Number Variations (CNVs), GC rich regions. We aimed to develop and validate a molecular diagnostic method in conjunction with the NGS platform as an inexpensive, extended and uniform coverage and fast screening tool which consists of nine genes known to be associated with various AIDs.
METHODS
For the validation of basic and expanded panels, long-range multiplex models were setup on healthy samples without any known variations for MEFV, MVK, TNFRSF1A, NLRP3, PSTPIP1, IL1RN, NOD2, NLRP12 and LPIN2 genes. Patients with AIDs who had already known causative variants in these genes were sequenced for analytical validation. As a last step, multiplex models were validated on patients with pre-diagnosis of AIDs. All sequencing steps were performed on the Illumina NGS platform. Validity steps included the selection of related candidate genes, primer design, development of screening methods, validation and verification of the product. The GDPE (Gentera) bioinformatics pipeline was followed.
RESULTS
Although there was no nonsynonymous variation in 21 healthy samples, 107 synonymous variant alleles and some intronic and UTR variants were detected. In 10 patients who underwent analytical validation, besides the 11 known nonsynonymous variant alleles, 11 additional nonsynonymous variant alleles and a total of 81 synonymous variants were found. In the clinical validation phase, 46 patients sequenced with multiplex panels, genetic and clinical findings were combined for diagnosis.
CONCLUSION
In this study, we describe the development and validation of an NGS-based multiplex array enabling the "long-amplicon" approach for targeted sequencing of nine genes associated with common AIDs. This screening tool is less expensive and more comprehensive compared to other methods and more informative than traditional sequencing. The proposed panel offers advantages to WES or hybridization probe equivalents in terms of CNV analysis, high sensitivity and uniformity, GC-rich region sequencing, InDel detection and intron covering.
Topics: Alleles; Genetic Testing; Genotype; Hereditary Autoinflammatory Diseases; High-Throughput Nucleotide Sequencing; Humans; Multiplex Polymerase Chain Reaction; Mutation; Reproducibility of Results; Sequence Analysis, DNA
PubMed: 34177904
DOI: 10.3389/fimmu.2021.666273 -
The Journal of Allergy and Clinical... Sep 2021Since its outbreak in late December 2019 in Wuhan, coronavirus disease 2019 pandemic has posed a therapeutic challenge for the world population, with a plenty of... (Review)
Review
Since its outbreak in late December 2019 in Wuhan, coronavirus disease 2019 pandemic has posed a therapeutic challenge for the world population, with a plenty of clinical pictures and a broad spectrum of severity of the manifestations. In spite of initial speculations on a direct role of primary or acquired immune deficiency in determining a worse disease outcome, recent studies have provided evidence that specific immune defects may either serve as an experimentum naturae entailing this risk or may not be relevant enough to impact the host defense against the virus. Taken together, these observations may help unveil pathogenetic mechanisms of the infection and suggest new therapeutic strategies. Thus, in this review, we summarize current knowledge regarding the mechanisms of immune response against severe acute respiratory syndrome coronavirus 2 infection and clinical manifestations with a special focus on children and patients presenting with congenital or acquired immune deficiency.
Topics: COVID-19; Child; Disease Outbreaks; Humans; Immunologic Deficiency Syndromes; Pandemics; SARS-CoV-2
PubMed: 34273582
DOI: 10.1016/j.jaip.2021.06.045 -
Neurology Research International 2021Cerebral palsy is the most common neurologic disorder of childhood with lifelong implications in majority of patients. Knowledge of the determinants of cerebral palsy is...
INTRODUCTION
Cerebral palsy is the most common neurologic disorder of childhood with lifelong implications in majority of patients. Knowledge of the determinants of cerebral palsy is important for accurate mobilization of resources in obstetric, perinatal, and infant care besides implementation of prevention systems. In Ethiopia, however, this knowledge gap exists as there are no published studies on determinants of cerebral palsy in the country.
OBJECTIVE
To assess the determinants of cerebral palsy in pediatric patients attending Ayder Comprehensive Specialized Referral Hospital between April 2019 and August 2019.
METHODS
An unmatched case-control study was conducted among 50 pediatric cerebral palsy patients and 100 controls, pediatric patients without cerebral palsy or other motor or central nervous system illnesses, attending Ayder Comprehensive Specialized Hospital, Mekelle, Ethiopia. The data were analyzed using SPSS version 27.
RESULTS
Significant factors were operative vaginal delivery (AOR: 9.49, 95% CI: 1.31-68.88), central nervous system infections (AOR: 0.02, 95% CI: 0-0.58), neonatal admissions (AOR: 0.13, 95% CI: 0.03-0.61), and unknown maternal education status (AOR: 18.64, 95% CI: 2.15-161.73).
CONCLUSION
Operative vaginal delivery, central nervous system infections in infancy, neonatal hospital admissions, and unknown maternal education status were found to be significant determinants for cerebral palsy. This knowledge aids focused hospital and regional health bureau development and implementation of prevention strategies for cerebral palsy, besides improvement of obstetric and neonatal healthcare services, and provides baseline data to the scientific community for further research.
PubMed: 34966561
DOI: 10.1155/2021/9993912 -
PloS One 2022HIV-focused organizations, care providers and research programs often hire Black gay, bisexual and other men who have sex with men (GBMSM) in their efforts to reach...
BACKGROUND
HIV-focused organizations, care providers and research programs often hire Black gay, bisexual and other men who have sex with men (GBMSM) in their efforts to reach highly affected communities. Due to their unique social position within and outside of organizations, Black GBMSM are ideally situated to contribute to HIV care and prevention programming targeting their own communities, but may also be at risk for stress and burnout in these settings. Despite this critical role for Black GBMSM in efforts to end the epidemic, little is known about subjective experiences of Black GBMSM who work in the HIV field.
METHODS
We conducted qualitative interviews with 19 Black GBMSM who were identified as key informants. All were working in community-based organizations, clinical or academic settings in the area of HIV prevention and treatment in Atlanta, Georgia. We used a thematic analysis approach to identify salient themes with respect to the workplace experiences of Black GBMSM as well as the role of their identities in their work in the field.
RESULTS
Participants discussed: (1) Shared experiences and growth; (2) Work-related stressors; (3) Worker burnout; and (4) Commitment to continue working in the HIV field. On the whole, Black GBMSM derived meaning from their work, and found their intersectional identities to be a strength in fulfilling job duties. At the same time, Black GBMSM described multiple stresses faced as they balanced their personal and professional connections to this work, while also dealing with their own challenges related to discrimination, socioeconomic status, and health. Participants repeatedly described sacrificing their own well-being for the greater good of their communities, highlighting contributors to burnout within and outside of the workplace.
CONCLUSIONS
Our participants derived meaning from their work in the HIV field and were affirmed by professional interactions with other Black GBMSM. At the same time, they also faced work-related and other psychosocial stressors that predisposed them to frustration and burnout. To promote workplace equity and wellness for Black GBMSM, we share recommendations for HIV-focused organizations that employ and serve men in this demographic.
Topics: Acquired Immunodeficiency Syndrome; Bisexuality; Burnout, Psychological; HIV Infections; Homosexuality, Male; Humans; Male; Qualitative Research; Sexual Behavior; Sexual and Gender Minorities
PubMed: 35947604
DOI: 10.1371/journal.pone.0264680 -
Scandinavian Journal of Immunology Nov 2020Behçet's disease (BD) is a heterogeneous multi-organ disorder in search of a unified pathophysiological theory and classification. The disease frequently has... (Review)
Review
Behçet's disease (BD) is a heterogeneous multi-organ disorder in search of a unified pathophysiological theory and classification. The disease frequently has overlapping features resembling other disease clusters, such as vasculitides, spondyloarthritides and thrombophilias with similar genetic risk variants, namely HLA-B*51, ERAP1, IL-10, IL-23R. Many of the BD manifestations, such as unprovoked recurrent episodes of inflammation and increased expression of IL-1, IL-6 and TNFα, overlap with those of the hereditary monogenic autoinflammatory syndromes, positioning BD at the crossroads between autoimmune and autoinflammatory syndromes. BD-like disease associates with various inborn errors of immunity, including familial Mediterranean fever, conditions related to dysregulated NF-κB activation (eg TNFAIP3, NFKB1, OTULIN, RELA, IKBKG) and either constitutional trisomy 8 or acquired trisomy 8 in myelodysplastic syndromes. We review here the recent advances in the immunopathology of BD, BD-like diseases and the NF-κB pathway suggesting new elements in the elusive BD etiopathogenesis.
Topics: Behcet Syndrome; Chromosomes, Human, Pair 8; Genetic Predisposition to Disease; Humans; Interleukin-10; Mouth Mucosa; NF-kappa B; Phenotype; Skin Ulcer; Trisomy
PubMed: 32889730
DOI: 10.1111/sji.12973