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The Cochrane Database of Systematic... Jan 2020Nosocomial infections continue to be a significant cause of morbidity and mortality among preterm and/or low birth weight (LBW) infants. Preterm infants are deficient in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Nosocomial infections continue to be a significant cause of morbidity and mortality among preterm and/or low birth weight (LBW) infants. Preterm infants are deficient in immunoglobulin G (IgG); therefore, administration of intravenous immunoglobulin (IVIG) may have the potential of preventing or altering the course of nosocomial infections.
OBJECTIVES
To use systematic review/meta-analytical techniques to determine whether IVIG administration (compared with placebo or no intervention) to preterm (< 37 weeks' postmenstrual age (PMA) at birth) or LBW (< 2500 g birth weight) infants or both is effective/safe in preventing nosocomial infection.
SEARCH METHODS
For this update, MEDLINE, EMBASE, CINAHL, The Cochrane Library, Controlled Trials, ClinicalTrials.gov and PAS Abstracts2view were searched in May 2013.
SELECTION CRITERIA
We selected randomised controlled trials (RCTs) in which a group of participants to whom IVIG was given was compared with a control group that received a placebo or no intervention for preterm (< 37 weeks' gestational age) and/or LBW (< 2500 g) infants. Studies that were primarily designed to assess the effect of IVIG on humoral immune markers were excluded, as were studies in which the follow-up period was one week or less.
DATA COLLECTION AND ANALYSIS
Data collection and analysis was performed in accordance with the methods of the Cochrane Neonatal Review Group.
MAIN RESULTS
Nineteen studies enrolling approximately 5000 preterm and/or LBW infants met inclusion criteria. No new trials were identified in May 2013. When all studies were combined, a significant reduction in sepsis was noted (typical risk ratio (RR) 0.85, 95% confidence interval (CI) 0.74 to 0.98; typical risk difference (RD) -0.03, 95% CI 0.00 to -0.05; number needed to treat for an additional beneficial outcome (NNTB) 33, 95% CI 20 to infinity), and moderate between-study heterogeneity was reported (I 54% for RR, 55% for RD). A significant reduction of one or more episodes was found for any serious infection when all studies were combined (typical RR 0.82, 95% CI 0.74 to 0.92; typical RD -0.04, 95% CI -0.02 to -0.06; NNTB 25, 95% CI 17 to 50), and moderate between-study heterogeneity was observed (I 50% for RR, 62% for RD). No statistically significant differences in mortality from all causes were noted (typical RR 0.89, 95% CI 0.75 to 1.05; typical RD -0.01, 95% CI -0.03 to 0.01), and no heterogeneity for RR (I = 21%) or low heterogeneity for RD was documented (I = 28%). No statistically significant difference was seen in mortality from infection; in incidence of necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD) or intraventricular haemorrhage (IVH) or in length of hospital stay. No major adverse effects of IVIG were reported in any of these studies.
AUTHORS' CONCLUSIONS
IVIG administration results in a 3% reduction in sepsis and a 4% reduction in one or more episodes of any serious infection but is not associated with reductions in other clinically important outcomes, including mortality. Prophylactic use of IVIG is not associated with any short-term serious side effects. The decision to use prophylactic IVIG will depend on the costs and the values assigned to the clinical outcomes. There is no justification for conducting additional RCTs to test the efficacy of previously studied IVIG preparations in reducing nosocomial infections in preterm and/or LBW infants.
Topics: Cross Infection; Humans; IgG Deficiency; Immunoglobulin G; Immunoglobulins, Intravenous; Infant; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Randomized Controlled Trials as Topic
PubMed: 31995650
DOI: 10.1002/14651858.CD000361.pub4 -
The Journal of Allergy and Clinical... Jan 2023SARS-CoV-2, the agent responsible for COVID-19, has wreaked havoc around the globe. Hundreds of millions of individuals have been infected and well over six million have...
SARS-CoV-2, the agent responsible for COVID-19, has wreaked havoc around the globe. Hundreds of millions of individuals have been infected and well over six million have died from COVID-19. Many COVID-19 survivors have ongoing physical and psychiatric morbidity, which will remain for the rest of their lives. Early in the pandemic, it became apparent that older individuals and those with comorbidities including obesity, diabetes mellitus, coronary artery disease, hypertension, and renal and pulmonary disease were at increased risk of adverse outcomes. It is also clear that some immunodeficient patients, such as those with innate or T cell-immune defects, are at greater risk from COVID-19. Selective IgA deficiency (sIgAD) is generally regarded as a mild disorder in which most patients are asymptomatic because of redundancy in protective immune mechanisms. Recent data indicate that patients with sIgAD may be at high risk of severe COVID-19. SARS-CoV-2 gains entry primarily through the upper respiratory tract mucosa, where IgA has a critical protective role. This may underlie the vulnerability of sIgAD patients to adverse outcomes from COVID-19. This perspective highlights the need for ongoing research into mucosal immunity to improve COVID-19 treatments for patients with sIgAD.
Topics: Humans; COVID-19; SARS-CoV-2; IgA Deficiency; Risk Factors
PubMed: 36241155
DOI: 10.1016/j.jaip.2022.10.002 -
Gut Microbes 2019In a recently published article we report the metagenomic analysis of human gut microbiomes evolved in the absence of immunoglobulin A (IgA). We show that human IgA...
In a recently published article we report the metagenomic analysis of human gut microbiomes evolved in the absence of immunoglobulin A (IgA). We show that human IgA deficiency is not associated with massive quantitative perturbations of gut microbial ecology. While our study underlines a rather expected pathobiont expansion, we at the same time highlight a less expected depletion in some typically beneficial symbionts. We also show that IgM partially supply IgA deficiency, explaining the relatively mild clinical phenotype associated with the early steps of this condition. Microbiome studies in patients should consider potential issues such as cohort size, human genetic polymorphism and treatments. In this commentary, we discuss how such issues were taken into account in our own study.
Topics: Bacteria; Biodiversity; Common Variable Immunodeficiency; Gastrointestinal Microbiome; Humans; IgA Deficiency; Immunoglobulin A; Immunoglobulin M
PubMed: 30449244
DOI: 10.1080/19490976.2018.1546520 -
BMJ Case Reports May 2017A 57-year-old woman with frequent respiratory infections was initially diagnosed with IgG subclass deficiency based on low levels of IgG subclasses 2 and 3. Three years...
A 57-year-old woman with frequent respiratory infections was initially diagnosed with IgG subclass deficiency based on low levels of IgG subclasses 2 and 3. Three years later, she progressed to having IgA deficiency as well. With a normal total IgG level, she does not meet criteria for common variable immunodeficiency (CVID). This may represent a variant of CVID. This also highlights the importance of immunoglobulin subclass estimation in patients where immunodeficiency is suspected clinically. She is being treated with rotational antibiotics the first 10 days of every month, monthly intravenous immunoglobulin (IVIG) infusion and osteopathic manipulation one to two times per month. On this regimen, although she has had several viral respiratory infections, she has avoided further hospitalisation for more than 1 year.
Topics: Anti-Bacterial Agents; Common Variable Immunodeficiency; Diagnosis, Differential; Female; Humans; IgA Deficiency; IgG Deficiency; Immunoglobulins, Intravenous; Middle Aged; Respiratory Tract Infections; Treatment Outcome
PubMed: 28551598
DOI: 10.1136/bcr-2017-219655 -
DNA Repair Jul 2016Activation-induced deoxycytidine deaminase (AID) initiates somatic hypermutation (SHM) and class-switch recombination (CSR) by deaminating C→U during transcription of...
Activation-induced deoxycytidine deaminase (AID) initiates somatic hypermutation (SHM) and class-switch recombination (CSR) by deaminating C→U during transcription of Ig-variable (V) and Ig-switch (S) region DNA, which is essential to produce high-affinity antibodies. Here we report the crystal structure of a soluble human AID variant at 2.8Å resolution that favors targeting WRC motifs (W=A/T, R=A/G) in vitro, and executes Ig V SHM in Ramos B-cells. A specificity loop extending away from the active site to accommodate two purine bases next to C, differs significantly in sequence, length, and conformation from APOBEC proteins Apo3A and Apo3G, which strongly favor pyrimidines at -1 and -2 positions. Individual amino acid contributions to specificity and processivity were measured in relation to a proposed ssDNA binding cleft. This study provides a structural basis for residue contributions to DNA scanning properties unique to AID, and for disease mutations in human HIGM-2 syndrome.
Topics: Amino Acid Sequence; Animals; B-Lymphocytes; Baculoviridae; Catalytic Domain; Cloning, Molecular; Crystallography, X-Ray; Cytidine Deaminase; Gene Expression; Humans; Hyper-IgM Immunodeficiency Syndrome; Immunoglobulin Class Switching; Immunoglobulins; Models, Molecular; Mutation; Protein Domains; Protein Structure, Secondary; Recombinant Proteins; Sf9 Cells; Somatic Hypermutation, Immunoglobulin; Spodoptera
PubMed: 27258794
DOI: 10.1016/j.dnarep.2016.05.029 -
Respiratory Research May 2022Immunoglobulin G (IgG) deficiency increases the risk of acute exacerbations and mortality in chronic obstructive pulmonary disease (COPD). However, the impact of IgG...
BACKGROUND
Immunoglobulin G (IgG) deficiency increases the risk of acute exacerbations and mortality in chronic obstructive pulmonary disease (COPD). However, the impact of IgG subclass deficiency on mortality in COPD is unknown. Here, we determined which IgG subclass, if any, is associated with increased risk of mortality in COPD.
METHODS
We measured serum IgG subclass concentrations of 489 hospitalized patients with COPD who were enrolled in the Rapid Transition Program (clinicaltrials.gov identifier NCT02050022). To evaluate the impact of IgG subclass deficiency on 1-year mortality, Cox proportional hazards regression analyses were performed with adjustments for potential confounders.
RESULTS
Deficiencies in IgG1, IgG2, IgG3, and IgG4 were present in 1.8%, 12.1%, 4.3%, and 11.2% of patients, respectively. One-year mortality was 56% in patients with IgG1 deficiency, 27% in IgG2 deficiency, 24% in IgG3 deficiency, and 31% in IgG4 deficiency. Cox proportional modeling showed that IgG1 and IgG4 deficiencies increased the 1-year mortality risk with an adjusted hazard ratio of 3.92 (95% confidence interval [CI] = 1.55-9.87) and 1.74 (95% CI = 1.02-2.98), respectively. Neither IgG2 nor IgG3 deficiency significantly increased 1-year mortality. Two or more IgG subclass deficiencies were observed in 5.3%. Patients with 2 or more IgG subclass deficiencies had a higher 1-year mortality than those without any deficiencies (46.2% vs. 19.7%, p < 0.001), with an adjusted hazard ratio of 2.22 (95% CI = 1.18-4.17).
CONCLUSIONS
IgG1 and IgG4 deficiency was observed in 1.8% and 11.2% of hospitalized patients with COPD, respectively, and these deficiencies were associated with a significantly increased risk of 1-year mortality.
Topics: Humans; IgG Deficiency; Immunoglobulin G; Immunologic Deficiency Syndromes; Pulmonary Disease, Chronic Obstructive
PubMed: 35641962
DOI: 10.1186/s12931-022-02052-3 -
Journal of Clinical Immunology Feb 2015XMEN disease (X-linked immunodeficiency with Magnesium defect, Epstein-Barr virus infection and Neoplasia) is a novel primary immune deficiency caused by mutations in... (Review)
Review
XMEN disease (X-linked immunodeficiency with Magnesium defect, Epstein-Barr virus infection and Neoplasia) is a novel primary immune deficiency caused by mutations in MAGT1 and characterised by chronic infection with Epstein-Barr virus (EBV), EBV-driven lymphoma, CD4 T-cell lymphopenia, and dysgammaglobulinemia [1]. Functional studies have demonstrated roles for magnesium as a second messenger in T-cell receptor signalling [1], and for NKG2D expression and consequently NK- and CD8 T-cell cytotoxicity [2]. 7 patients have been described in the literature; the oldest died at 45 years and was diagnosed posthumously [1-3]. We present the case of a 58-year-old Caucasian gentleman with a novel mutation in MAGT1 with the aim of adding to the phenotype of this newly described disease by detailing his clinical course over more than 20 years.
Topics: Brain; Cation Transport Proteins; DNA Mutational Analysis; Fluorodeoxyglucose F18; Humans; Immunophenotyping; Leukoencephalopathy, Progressive Multifocal; Lymph Nodes; Magnetic Resonance Imaging; Male; Middle Aged; Mutation; Phenotype; Positron-Emission Tomography; T-Lymphocyte Subsets; Tomography, X-Ray Computed; X-Linked Combined Immunodeficiency Diseases
PubMed: 25504528
DOI: 10.1007/s10875-014-0116-2 -
Journal of Clinical Immunology Jul 2016The United States Immunodeficiency Network (USIDNET) patient registry was used to characterize the presentation, genetics, phenotypes, and treatment of patients with...
PURPOSE
The United States Immunodeficiency Network (USIDNET) patient registry was used to characterize the presentation, genetics, phenotypes, and treatment of patients with Hyper IgM Syndrome (HIGM).
METHODS
The USIDNET Registry was queried for HIGM patient data collected from October 1992 to July 2015. Data fields included demographics, criteria for diagnosis, pedigree analysis, mutations, clinical features, treatment and transplant records, laboratory findings, and mortality.
RESULTS
Fifty-two physicians entered data from 145 patients of ages 2 months to 62 years (median 12 years); 131 were males. Using patients' age at last entry, data from 2072 patient years are included. Mutations were recorded for 85 subjects; 82 were in CD40LG. Eighteen subjects had non-X-linked HIGM. 40 % had a normal serum IgM and 15 %, normal IgA. Infections were reported for 91 %, with pulmonary, ear, and sinus infections being the most common. 42 % had Pneumocystis jirovecii pneumonia; 6 % had Cryptosporidium. 41 % had neutropenia. 78 % experienced non-infectious complications: chronic diarrhea (n = 22), aphthous ulcers (n = 28), and neoplasms (n = 8) including colon cancer, adrenal adenoma, liver adenocarcinoma, pancreatic carcinoid, acute myeloid leukemia, hepatoma, and, in a female with an autosomal dominant gain of function mutation in PIK3CD, an ovarian dysgerminoma. Thirteen patients had a hematopoietic marrow or stem cell transplant; three had solid organ transplants. Thirteen were known to have died (median age = 14 years).
CONCLUSIONS
Analysis of the USIDNET Registry provides data on the common clinical features of this rare syndrome, and in contrast with previously published data, demonstrates longer survival times and reduced gastrointestinal manifestations.
Topics: Adolescent; Adult; CD40 Ligand; Child; Child, Preschool; Diarrhea; Female; Hematopoietic Stem Cell Transplantation; Humans; Hyper-IgM Immunodeficiency Syndrome; Male; Middle Aged; Mutation; Neutropenia; Registries; Survival Analysis; United States; Young Adult
PubMed: 27189378
DOI: 10.1007/s10875-016-0291-4 -
BMC Pediatrics Apr 2022Hyper IgM syndromes (HIGMS) are a group of rare primary immunodeficiency disorders. There are limited reports about HIGMS combined with severe eosinophilia. (Review)
Review
BACKGROUND
Hyper IgM syndromes (HIGMS) are a group of rare primary immunodeficiency disorders. There are limited reports about HIGMS combined with severe eosinophilia.
CASE PRESENTATION
In this report, we described a 2-year-old boy with chronic cough and symptoms of hypoxia. Lung computed tomography (CT) scan showed that diffuse ground-glass changes and eosinophils in peripheral blood increased significantly. Subsequent tests revealed a notable decrease in serum IgG and IgA. The lymphocyte subgroup classification was basically normal. Pneumocystis jirovecii were detected from the bronchoalveolar lavage fluid (BALF) of the patient by metagenomic next-generation sequencing (mNGS). After treatments of caspofungin combined with sulfamethoxazole, intravenous immunoglobulin (IVIG) replacement and anti-inflammatory steroid, the clinical symptoms and pulmonary imaging noticeably improved. The absolute eosinophil count (AEC) also returned to normal range. X-linked hyper IgM syndrome was confirmed by gene test. Two months after the diagnosis, the patient underwent allogeneic stem cell transplantation (HSCT) and has recovered well.
CONCLUSIONS
Children with HIGMS are prone to opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP). Diffuse interstitial lung disease and hypoglobulinemia in a young child predict the diagnosis of a primary immunodeficiency (PID). mNGS has obvious advantages for obtaining etiological diagnosis of children with PIDs. Severe eosinophilia is rarely reported in this kind of PIDs. Considering literature review and the corresponding reaction to steroid, we proposed that eosinophilia in HIGMS might be related to infections. Steroid therapy can quickly relieve eosinophilia but is easy to rebound if the reduction is too fast. Once the diagnosis of HIGMS is confirmed, the earlier the HSCT, the better the prognosis.
Topics: Anti-Inflammatory Agents; Child; Child, Preschool; Eosinophilia; Hematopoietic Stem Cell Transplantation; Humans; Hyper-IgM Immunodeficiency Syndrome; Hyper-IgM Immunodeficiency Syndrome, Type 1; Male
PubMed: 35379217
DOI: 10.1186/s12887-022-03251-z -
Journal of Clinical Immunology Feb 2024B cells and their secreted antibodies are fundamental for host-defense against pathogens. The generation of high-affinity class switched antibodies results from both...
B cells and their secreted antibodies are fundamental for host-defense against pathogens. The generation of high-affinity class switched antibodies results from both somatic hypermutation (SHM) of the immunoglobulin (Ig) variable region genes of the B-cell receptor and class switch recombination (CSR) which alters the Ig heavy chain constant region. Both of these processes are initiated by the enzyme activation-induced cytidine deaminase (AID), encoded by AICDA. Deleterious variants in AICDA are causal of hyper-IgM syndrome type 2 (HIGM2), a B-cell intrinsic primary immunodeficiency characterised by recurrent infections and low serum IgG and IgA levels. Biallelic variants affecting exons 2, 3 or 4 of AICDA have been identified that impair both CSR and SHM in patients with autosomal recessive HIGM2. Interestingly, B cells from patients with autosomal dominant HIGM2, caused by heterozygous variants (V186X, R190X) located in AICDA exon 5 encoding the nuclear export signal (NES) domain, show abolished CSR but variable SHM. We herein report the immunological and functional phenotype of two related patients presenting with common variable immunodeficiency who were found to have a novel heterozygous variant in AICDA (L189X). This variant led to a truncated AID protein lacking the last 10 amino acids of the NES at the C-terminal domain. Interestingly, patients' B cells carrying the L189X variant exhibited not only greatly impaired CSR but also SHM in vivo, as well as CSR and production of IgG and IgA in vitro. Our findings demonstrate that the NES domain of AID can be essential for SHM, as well as for CSR, thereby refining the correlation between AICDA genotype and SHM phenotype as well as broadening our understanding of the pathophysiology of HIGM disorders.
Topics: Humans; Cytidine Deaminase; Hyper-IgM Immunodeficiency Syndrome; Immunoglobulin A; Immunoglobulin Class Switching; Immunoglobulin G; Phenotype; Somatic Hypermutation, Immunoglobulin
PubMed: 38363477
DOI: 10.1007/s10875-024-01665-1