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Frontiers in Immunology 2021B cell differentiation and memory are controlled by the transmembrane activator and CAML interactor (TACI), a receptor encoded by . mutations are frequently found in...
B cell differentiation and memory are controlled by the transmembrane activator and CAML interactor (TACI), a receptor encoded by . mutations are frequently found in common variable immunodeficiency (CVID) and in IgA -deficiency; yet, ~98% of those with mutant are healthy. Indeed, is among the 5% most polymorphic genes in man. Other mammals evidence polymorphism at comparable loci. We hypothesize that diversity might promote rather than detract from well-being by controlling key elements of innate immunity. We shall discuss how extraordinary diversity of could have evolved and persisted across diverse species of mammals by controlling innate and adaptive B cell responses in apparently paradoxical ways.
Topics: Adaptive Immunity; Animals; Antibodies; B-Lymphocytes; Common Variable Immunodeficiency; Evolution, Molecular; Genetic Predisposition to Disease; Humans; IgA Deficiency; Immunity, Innate; Mutation; Phenotype; Transmembrane Activator and CAML Interactor Protein
PubMed: 33679786
DOI: 10.3389/fimmu.2021.634544 -
Science Translational Medicine May 2018Paradoxically, loss of immunoglobulin A (IgA), one of the most abundant antibodies, does not irrevocably lead to severe infections in humans but rather is associated...
Paradoxically, loss of immunoglobulin A (IgA), one of the most abundant antibodies, does not irrevocably lead to severe infections in humans but rather is associated with relatively mild respiratory infections, atopy, and autoimmunity. IgA might therefore also play covert roles, not uniquely associated with control of pathogens. We show that human IgA deficiency is not associated with massive quantitative perturbations of gut microbial ecology. Metagenomic analysis highlights an expected pathobiont expansion but a less expected depletion in some typically beneficial symbionts. Gut colonization by species usually present in the oropharynx is also reminiscent of spatial microbiota disorganization. IgM only partially rescues IgA deficiency because not all typical IgA targets are efficiently bound by IgM in the intestinal lumen. Together, IgA appears to play a nonredundant role at the forefront of the immune/microbial interface, away from the intestinal barrier, ranging from pathobiont control and regulation of systemic inflammation to preservation of commensal diversity and community networks.
Topics: Humans; IgA Deficiency; Immunoglobulin A; Immunoglobulin M; Microbiota
PubMed: 29720448
DOI: 10.1126/scitranslmed.aan1217 -
Journal of Investigational Allergology... 2015Selective immunoglobulin A deficiency (SIgAD) is the most common primary antibody deticiency. Patients with SIgAD have a greater risk of concomitant autoimmune disorders...
BACKGROUND AND OBJECTIVE
Selective immunoglobulin A deficiency (SIgAD) is the most common primary antibody deticiency. Patients with SIgAD have a greater risk of concomitant autoimmune disorders than healthy individuals. The exact mechanism underlying the relationship between autoimmunity and SIgAD is not fully understood. The aim of this study was to evaluate potential associations between autoimmunity and specific clinical or immunological findings in patients with SIgAD.
METHODS
The study population comprised 57 symptomatic patients (65% males) with confirmed SIgAD who were referred to our center. Demographic data and history of autoimmunity were recorded both for patients and for their relatives. Comprehensive clinical and laboratory examinations were performed to investigate autoimmune complications in all the patients.
RESULTS
Autoimmune disorders were documented in 17 cases (29.8%; 9 males and 8 females). The most common manifestations were thyroiditis, vitiligo, and hemolytic anemia (3 cases each). Ten patients (17.5%) had a family history of autoimmunity. Significant associations were detected between autoimmunity and increased duration of follow-up (P = .003), serum level of IgM (P = .01), regulatory T-cell count (P = .03), and class-switched memory B-cell count (P = .01). Four cases of autoimmune SIgAD (23.5%) progressed to common variable immunodeficiency during the follow-up period (P = .006).
CONCLUSIONS
Autoimmune disorders, autoimmune cytopenia, and Ig subclass deficiency can lead to severe clinical manifestations in patients with SIgAD. Therefore, immunologists and pediatricians should be aware of these conditions.
Topics: Adolescent; Autoimmune Diseases; Autoimmunity; B-Lymphocytes; Child; Child, Preschool; Female; Humans; IgA Deficiency; Immunoglobulin M; Immunologic Memory; Incidence; Iran; Lymphocyte Count; Male; Predictive Value of Tests; Prevalence; Prognosis; Risk Factors; T-Lymphocytes, Regulatory
PubMed: 25997304
DOI: No ID Found -
QJM : Monthly Journal of the... May 2022Immunoglobulin G (IgG) subclass 2 deficiency is the most frequent IgG subclass deficiency identified in patients with bronchiectasis, but its clinical significance is...
BACKGROUND
Immunoglobulin G (IgG) subclass 2 deficiency is the most frequent IgG subclass deficiency identified in patients with bronchiectasis, but its clinical significance is not known.
AIM
To analyse if bronchiectasis patients with isolated IgG2 deficiency at risk of recurrent exacerbations and/or hospitalization? Do patients with IgG2 deficiency have worse disease progression?
DESIGN AND METHODS
This is a retrospective study (2015-20) exploring independent risk factors for recurrent exacerbations (3 or more per year) and/or hospitalization with bronchiectasis exacerbations using multivariable models using binary logistic regression. There was no patient with IgG deficiency, IgG 1, 3 or 4 deficiency, or IgA or IgM deficiency included. In this model, the authors included: serum IgG2 level; lung function; body mass index; MRC breathlessness scale; age; sex; number of bronchiectatic lobes; bacterial colonization; comorbidities; and the use of long-term immunosuppressant drugs or antibiotics for more than 28 days. Analysing 2-year longitudinal data, one-way ANOVA and Mann-Whitney U-test were used to compare bronchiectasis severity between patients with different IgG2 levels.
RESULTS
Serum IgG2 levels (<2.68 g/l, 2.68-3.53 g/l and 3.54-4.45 g/l); hospital admission in the preceding 2 years; bacterial colonization with potentially pathogenic organisms and asthma were independent predictors for three or more bronchiectasis exacerbations. Those with low IgG2 levels (<2.68 g/l and 2.68-3.53 g/l), had worsening progression of their bronchiectasis, using the Bronchiectasis Severity Index, over 1 year compared with those who were IgG2 replete (>4.45 g/l) (P = 0.003, 0.013).
CONCLUSION
Reduced IgG2 levels were an independent predictor for bronchiectasis exacerbations and have increased disease progression.
Topics: Bronchiectasis; Disease Progression; Humans; IgG Deficiency; Immunoglobulin G; Retrospective Studies; Risk Factors
PubMed: 33970283
DOI: 10.1093/qjmed/hcab129 -
Zhongguo Dang Dai Er Ke Za Zhi =... Jun 2022To evaluate the clinical effect of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with hyper-IgM syndrome (HIGM).
OBJECTIVES
To evaluate the clinical effect of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with hyper-IgM syndrome (HIGM).
METHODS
A retrospective analysis was performed on the medical data of 17 children with HIGM who received allo-HSCT. The Kaplan Meier method was used for the survival analysis of the children with HIGM after allo-HSCT.
RESULTS
After allo-HSCT, 16 children were diagnosed with sepsis; 14 tested positive for virus within 100 days after allo-HSCT, among whom 11 were positive for Epstein-Barr virus, 7 were positive for cytomegalovirus, and 2 were positive for JC virus; 9 children were found to have invasive fungal disease. There were 6 children with acute graft-versus-host disease and 3 children with chronic graft-versus-host disease. The median follow-up time was about 2 years, and 3 children died in the early stage after allo-HSCT. The children had an overall survival (OS) rate of 82.35%, an event-free survival (EFS) rate of 70.59%, and a disease-free survival (DFS) rate of 76.47%. The univariate analysis showed that the children receiving HLA-matched allo-HSCT had a significantly higher EFS rate than those receiving HLA-mismatched allo-HSCT (=0.019) and that the children receiving HLA-matched unrelated allo-HSCT had significantly higher OS, EFS, and DFS rates than those receiving HLA-mismatched unrelated allo-HSCT (<0.05). Compared with the children with fungal infection after allo-HSCT, the children without fungal infection had significantly higher EFS rate (=0.02) and DFS rate (=0.04).
CONCLUSIONS
Allo-HSCT is an effective treatment method for children with HIGM. HLA-matched allo-HSCT and active prevention and treatment of fungal infection and opportunistic infection may help to improve the prognosis of such children.
Topics: Child; Epstein-Barr Virus Infections; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Herpesvirus 4, Human; Humans; Hyper-IgM Immunodeficiency Syndrome; Retrospective Studies
PubMed: 35762429
DOI: 10.7499/j.issn.1008-8830.2112098 -
Clinical and Experimental Immunology Jun 2016Selective immunoglobulin A (IgA) deficiency (IgAD) is the most common primary immunodeficiency in the western world. The aim of the study was to investigate the...
Selective immunoglobulin A (IgA) deficiency (IgAD) is the most common primary immunodeficiency in the western world. The aim of the study was to investigate the prevalence and clinical characteristics of Helicobacter pylori-infected dyspeptic patients with IgAD. Case samples were drawn from all subjects ≥ 12 years of age (n = 104729) who had undergone serum total IgA measurements during 2004-14 for any reason at Leumit Healthcare Services (Israel) and had serum total IgA < 0·07 g/l. The control group was comprised of a random sample of remaining patients with a case-control ratio of 10 controls for each case. The dyspeptic diseases were identified and retrieved from Leumit Health Care Services electronic database using specific ICD-9-CM diagnostic codes. The case group included 347 subjects and the control group 3470 subjects. There were no significant differences in the prevalence of patients with dyspepsia [84 (24·2%) versus 821 (23·6%) for cases and controls, respectively]. Additionally, there was no difference in a proportion of dyspeptic H. pylori-positive subjects [59 (17·1%) versus 524 (15·1%)] between the case and control groups. Only 59 (17%) among the 347 IgAD patients underwent gastroscopy. A significantly larger proportion of case subjects experienced several forms of gastritis [13 (61·9%) versus 38 (21·6%), P < 0·001), duodenal ulcers [seven (33·3%) versus 19 (10·8%); P = 0·01] and nodular lymphoid hyperplasia (NLH) [two (9·5%) versus none; P = 0·011]. IgAD is not associated with increased prevalence of H. pylori-associated dyspepsia; nevertheless, H. pylori-infected dyspeptic IgAD subjects experience more EGD-proved gastritis, duodenal ulcers and NLH.
Topics: Adolescent; Adult; Aged; Case-Control Studies; Castleman Disease; Child; Databases, Factual; Duodenal Ulcer; Dyspepsia; Electronic Health Records; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; IgA Deficiency; Immunoglobulin A; Israel; Middle Aged
PubMed: 26749258
DOI: 10.1111/cei.12765 -
Turkish Journal of Medical Sciences Apr 2017IgA deficiency is the most common human primary immunodeficiency. The prevalence of allergic disorders and autoimmunity is thought to be increased in selective IgA...
BACKGROUND/AIM
IgA deficiency is the most common human primary immunodeficiency. The prevalence of allergic disorders and autoimmunity is thought to be increased in selective IgA deficiency (sIgAD). However, it is currently unclear if these disorders coincide within these families. We aimed to evaluate the frequency of allergic and autoimmune disorders in children with sIgAD and their first-degree relatives (FDRs).
MATERIALS AND METHODS
The study included 81 children diagnosed with sIgAD and 274 of their FDRs. The presence of allergic and autoimmune disorders was evaluated and serum antithyroglobulin and antithyroid peroxidase levels were measured in both patients and their first-degree relatives.
RESULTS
The mean age of the patients was 9.9 ± 3.9 years. Among the patients with sIgAD, 45.7% of them had at least one allergic disorder and 17.3% of them had at least one autoimmune disorder. The frequencies of asthma, allergic rhinitis, and eczema in the FDRs of sIgAD patients were 10.9%, 9.1%, and 7.7%, respectively. Among their FDRs, 14.6% had autoimmunity, compared to an estimate of 5% in the general population.
CONCLUSION
Increased frequency of allergic and autoimmune disorders in patients with sIgAD and their FDRs suggests a possible common predisposing genetic component for sIgAD and autoimmunity in these families.
Topics: Adolescent; Adult; Autoantibodies; Autoimmune Diseases; Child; Cohort Studies; Family; Female; Humans; Hypersensitivity; IgA Deficiency; Male; Young Adult
PubMed: 28425252
DOI: 10.3906/sag-1605-50 -
Bone Marrow Transplantation Feb 2021CD19-CAR T-cell therapy (CART19) causes B-cell aplasia (BCA) and dysgammaglobulinemia but there is a lack of information about the degree of its secondary...
CD19-CAR T-cell therapy (CART19) causes B-cell aplasia (BCA) and dysgammaglobulinemia but there is a lack of information about the degree of its secondary immunodeficiency. We conducted a prospective study in children and young adults with acute lymphoblastic leukaemia treated with CART19, analysing the kinetics of BCA and dysgammaglobulinemia during therapy, as well as the B-cell reconstitution in those with CART19 loss. Thirty-four patients were included (14 female) with a median age at CART19 infusion of 8.7 years (2.9-24.9). Median follow-up after infusion was 7.1 months (0.5-42). BCA was observed 7 days after infusion (3-8), with persistence at 24 months in 60% of patients. All patients developed a progressive decrease in IgM and IgA: 71% had undetectable IgM levels at 71 days (41-99) and 13% undetectable IgA levels at 185 days (11-308). Three of 12 patients had protective levels of IgA in saliva. In two of three patients who lost CART19, persistent B-cell dysfunction was observed. No severe infections occurred. In conclusion, BCA occurs soon after CART19 infusion, with a progressive decrease in IgM and IgA, and with less impairment of IgA, suggesting the possibility of an immune reservoir. A persistent B-cell dysfunction might persist after CART19 loss in this population.
Topics: Antigens, CD19; Child; Female; Humans; Immunotherapy, Adoptive; Kinetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies; Young Adult
PubMed: 32801317
DOI: 10.1038/s41409-020-01027-6 -
Frontiers in Immunology 2018Patients with primary immunoglobulin deficiency have lower immunoglobulin levels or decreased immunoglobulin function, which makes these patients more susceptible to... (Review)
Review
Limited Innovations After More Than 65 Years of Immunoglobulin Replacement Therapy: Potential of IgA- and IgM-Enriched Formulations to Prevent Bacterial Respiratory Tract Infections.
Patients with primary immunoglobulin deficiency have lower immunoglobulin levels or decreased immunoglobulin function, which makes these patients more susceptible to bacterial infection. Most prevalent are the selective IgA deficiencies (~1:3,000), followed by common variable immune deficiency (~1:25,000). Agammaglobulinemia is less common (~1:400,000) and is characterized by very low or no immunoglobulin production resulting in a more severe disease phenotype. Therapy for patients with agammaglobulinemia mainly relies on prophylactic antibiotics and the use of IgG replacement therapy, which successfully reduces the frequency of invasive bacterial infections. Currently used immunoglobulin preparations contain only IgG. As a result, concurrent IgA and IgM deficiency persist in a large proportion of agammaglobulinemia patients. Especially patients with IgM deficiency remain at risk for recurrent infections at mucosal surfaces, which includes the respiratory tract. IgA and IgM have multiple functions in the protection against bacterial infections at the mucosal surface. Because of their multimeric structure, both IgA and IgM are able to agglutinate bacteria efficiently. Agglutination allows for entrapment of bacteria in mucus that increases clearance from the respiratory tract. IgA is also important for blocking bacterial adhesion by interfering with bacterial adhesion receptors. IgM in its place is very well capable of activating complement, therefore, it is thought to be important in complement-mediated protection at the mucosal surface. The purpose of this Mini Review is to highlight the latest advances regarding IgA- and IgM-enriched immunoglobulin replacement therapy. We describe the different IgA- and IgM-enriched IgG formulations, their possible modes of action and potential to protect against respiratory tract infections in patients with primary immunoglobulin deficiencies.
Topics: Bacterial Infections; History, 20th Century; History, 21st Century; Humans; IgA Deficiency; Immunization, Passive; Immunoglobulin A; Immunoglobulin M; Respiratory Tract Infections
PubMed: 30190722
DOI: 10.3389/fimmu.2018.01925 -
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