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European Journal of Pediatrics Jun 2011Primary antibody deficiencies (PADs) are the most common primary immunodeficiencies and are characterized by a defect in the production of normal amounts of... (Review)
Review
Primary antibody deficiencies (PADs) are the most common primary immunodeficiencies and are characterized by a defect in the production of normal amounts of antigen-specific antibodies. PADs represent a heterogeneous spectrum of conditions, ranging from often asymptomatic selective IgA and IgG subclass deficiencies to the severe congenital agammaglobulinemias, in which the antibody production of all immunoglobulin isotypes is severely decreased. Apart from recurrent respiratory tract infections, PADs are associated with a wide range of other clinical complications. This review will describe the pathophysiology, diagnosis, and treatment of the different PADs.
Topics: Agammaglobulinemia; Antibodies; Child; Diagnosis, Differential; Humans; IgA Deficiency; IgG Deficiency; Respiratory Tract Infections; Treatment Outcome
PubMed: 21544519
DOI: 10.1007/s00431-011-1474-x -
Scientific Reports Jul 2021Immunoglobulin A (IgA) is the dominant antibody found in our mucosal secretions and has long been recognized to play an important role in protecting our epithelium from...
Immunoglobulin A (IgA) is the dominant antibody found in our mucosal secretions and has long been recognized to play an important role in protecting our epithelium from pathogens. Recently, IgA has been shown to be involved in gut homeostatic regulation by 'recognizing' and shaping our commensal microbes. Paradoxically, yet selective IgA-deficiency is often described as asymptomatic and there is a paucity of studies only focused on the mice and human gut microbiome context fully ignoring other niches of our body and our commensal viruses. Here, we used as a model the human oral cavity and employed a holistic view and studied the impact of IgA deficiency and also common variable IgA and IgM immunodeficiencies (CVID), on both the human virome and microbiome. Unexpectedly, metagenomic and experimental data in human IgA deficiency and CVID indicate minimal-moderate changes in microbiome and virome composition compared to healthy control group and point out to a rather functional, resilient oral commensal viruses and microbes. However, a significant depletion (two fold) of bacterial cells (p-value < 0.01) and viruses was observed in IgA-deficiency. Our results demonstrate that, within the limits of our cohort, IgA role is not critical for maintaining a rather functional salivary microbiome and suggest that IgA is not a major influence on the composition of abundant commensal microbes.
Topics: Adolescent; Adult; Aged; Child; Female; Humans; IgA Deficiency; Immunoglobulin A; Immunoglobulin M; Male; Metagenomics; Microbiota; Middle Aged; Mouth; Saliva; Virome; Young Adult
PubMed: 34290346
DOI: 10.1038/s41598-021-94507-8 -
Nihon Rinsho Men'eki Gakkai Kaishi =... Jun 2009There are two subclasses of IgA, IgA1 and IgA2, and its heavy chains are encoded by two different genes, alpha1 and alpha2 genes. These two subclasses play important... (Review)
Review
There are two subclasses of IgA, IgA1 and IgA2, and its heavy chains are encoded by two different genes, alpha1 and alpha2 genes. These two subclasses play important roles in the first line of defense, and the amount ratio of these molecules in secretions varies. IgA deficiency (IgAD) is the most common immunodeficiency, however the pathogenesis in most cases of IgAD is unknown. The class switch disorder in IgA producing B lymphocytes is one of the important factors in IgAD patients. The decreased expression levels of Ialpha germline transcripts before a class switch may be the cause of selective IgAD. The alpha1 and alpha2 gene expression levels are low in most IgAD patients. Using RT-PCR method in which alpha1 and alpha2 mRNAs can be separately evaluated, we identified the second case of alpha1 gene deletion in Japan. Longitudinal change in the serum IgA of the patient with alpha1 gene deletion showed the pattern of the partial IgAD. Patients with alpha1 gene deletion can be considered as having partial IgAD.
Topics: Humans; IgA Deficiency; Immunoglobulin A; Transcription, Genetic
PubMed: 19564710
DOI: 10.2177/jsci.32.142 -
Hypertension (Dallas, Tex. : 1979) Oct 2022The spontaneously hypertensive rat (SHR) is extensively used to study hypertension. Gut microbiota dysbiosis is a notable feature in SHR for reasons unknown....
BACKGROUND
The spontaneously hypertensive rat (SHR) is extensively used to study hypertension. Gut microbiota dysbiosis is a notable feature in SHR for reasons unknown. Immunoglobulin A (IgA) is a major host factor required for gut microbiota homeostasis. We hypothesized that inadequate IgA contributes to gut microbiota dysbiosis in SHR.
METHODS
IgA was measured in feces, cecum, serum, liver, gut-associated lymphoid tissue, and milk from SHR and Wistar Kyoto rats. IgA regulatory factors like IgM, IgG, and (polymeric immunoglobulin receptor) were analyzed. IgA and IgG antibodies and blood pressure (BP) were measured before and after administrating a bacterial antigen (ie, flagellin).
RESULTS
Compared with Wistar Kyoto rats, SHR displayed remarkably near-deficient IgA levels accompanied by compensatory increases in serum IgM and IgG and gut-liver expression. Inadequate milk IgA in SHR emphasized this immune defect stemmed from the neonatal stage. Reduced IgA B cells in circulation and Peyer patches indicated a possible reason for the lower IgA in SHR. Noteworthy, a genetic insufficiency was unlikely because administering flagellin to SHR induced anti-flagellin IgA antibodies. This immune response surprisingly accelerated hypertension development in SHR, suggesting IgA quiescence may help maintain lower BP.
CONCLUSIONS
This study is the first to reveal IgA deficiency in SHR as one host factor associated with gut microbiota dysbiosis and invigorates future research to determine the pathophysiological role of IgA in hypertension.
Topics: Animals; Blood Pressure; Dysbiosis; Hypertension; IgA Deficiency; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Rats; Rats, Inbred SHR; Rats, Inbred WKY
PubMed: 35950503
DOI: 10.1161/HYPERTENSIONAHA.122.19307 -
Frontiers in Immunology 2022IgA deficiency is the commonest immunodeficiency affecting up to 1 in 700 individuals. The effects of IgA deficiency are difficult to see in many individuals, are mild... (Review)
Review
IgA deficiency is the commonest immunodeficiency affecting up to 1 in 700 individuals. The effects of IgA deficiency are difficult to see in many individuals, are mild in many fewer and severe in fewer still. While monovalent IgA is found in serum, dimeric IgA is secreted through mucosal surfaces where it helps to maintain epithelial homeostasis. Studies with knockout mice have taught us that there are subtle inflammatory consequences of removing secretory IgA (sIgA), and the best explanation for these changes can be related by the loss of the 'excretory' immune system. The excretion of antigens is a logical process in regulating the immune system, given the long half-life of complement fixing antibodies. But the function of IgA as an immune or inflammation regulator may go beyond antigen removal.
Topics: Mice; Animals; IgA Deficiency; Immunoglobulin A, Secretory; Mucous Membrane; Biological Transport; Mice, Knockout
PubMed: 36618388
DOI: 10.3389/fimmu.2022.1076312 -
Journal of Clinical Immunology Nov 2021Patients with ataxia-telangiectasia (A-T) suffer from progressive cerebellar ataxia, immunodeficiency, respiratory failure, and cancer susceptibility. From a clinical... (Clinical Trial)
Clinical Trial
Patients with ataxia-telangiectasia (A-T) suffer from progressive cerebellar ataxia, immunodeficiency, respiratory failure, and cancer susceptibility. From a clinical point of view, A-T patients with IgA deficiency show more symptoms and may have a poorer prognosis. In this study, we analyzed mortality and immunity data of 659 A-T patients with regard to IgA deficiency collected from the European Society for Immunodeficiencies (ESID) registry and from 66 patients with classical A-T who attended at the Frankfurt Goethe-University between 2012 and 2018. We studied peripheral B- and T-cell subsets and T-cell repertoire of the Frankfurt cohort and survival rates of all A-T patients in the ESID registry. Patients with A-T have significant alterations in their lymphocyte phenotypes. All subsets (CD3, CD4, CD8, CD19, CD4/CD45RA, and CD8/CD45RA) were significantly diminished compared to standard values. Patients with IgA deficiency (n = 35) had significantly lower lymphocyte counts compared to A-T patients without IgA deficiency (n = 31) due to a further decrease of naïve CD4 T-cells, central memory CD4 cells, and regulatory T-cells. Although both patient groups showed affected TCR-ß repertoires compared to controls, no differences could be detected between patients with and without IgA deficiency. Overall survival of patients with IgA deficiency was significantly diminished. For the first time, our data show that patients with IgA deficiency have significantly lower lymphocyte counts and subsets, which are accompanied with reduced survival, compared to A-T patients without IgA deficiency. IgA, a simple surrogate marker, is indicating the poorest prognosis for classical A-T patients. Both non-interventional clinical trials were registered at clinicaltrials.gov 2012 (Susceptibility to infections in ataxia-telangiectasia; NCT02345135) and 2017 (Susceptibility to Infections, tumor risk and liver disease in patients with ataxia-telangiectasia; NCT03357978).
Topics: Adolescent; Adult; Ataxia Telangiectasia; B-Lymphocytes; Child; Child, Preschool; Female; Humans; IgA Deficiency; IgG Deficiency; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Infant; Lymphocyte Count; Male; Middle Aged; T-Lymphocyte Subsets; Young Adult
PubMed: 34477998
DOI: 10.1007/s10875-021-01090-8 -
Journal of Child and Adolescent... May 2019Inflammation and immune dysregulation have been implicated in the pathogenesis of pediatric-onset obsessive-compulsive disorder (OCD) and tic disorders such as Tourette...
Inflammation and immune dysregulation have been implicated in the pathogenesis of pediatric-onset obsessive-compulsive disorder (OCD) and tic disorders such as Tourette syndrome (TS). Though few replicated studies have identified markers of immune dysfunction in this population, preliminary studies suggest that serum immunoglobulin A (IgA) concentrations may be abnormal in these children with these disorders. This observational retrospective cohort study, conducted using electronic health records (EHRs), identified 206 children with pediatric-onset OCD and 1024 adults diagnosed with OCD who also had testing for serum levels of IgA. IgA deficiency and serum IgA levels in pediatric OCD were compared with IgA levels from children diagnosed with autism spectrum disorders (ASD; = 524), tic disorders ( = 157), attention-deficit/hyperactivity disorder (ADHD; = 534), anxiety disorders ( = 1206), and celiac disease, a condition associated with IgA deficiency ( = 624). Compared with ASD and anxiety disorder cohorts, the pediatric OCD cohort displayed a significantly higher likelihood of IgA deficiency (OR = 1.93; 95% CI = 1.18-3.16, and OR = 1.98; 95% CI = 1.28-3.06, respectively), though no difference was observed between pediatric OCD and TS cohorts. Furthermore, the pediatric OCD cohort displayed similar rates of IgA deficiency and serum IgA levels when compared with the celiac disease cohort. The pediatric OCD cohort also displayed the highest percentage of IgA deficiency (15%,) when compared with TS (14%), celiac disease (14%), ADHD (13%), ASD (8%), and anxiety disorder (8%) cohorts. When segregated by sex, boys with OCD displayed a significantly higher likelihood of IgA deficiency when compared with all comparison cohorts except for celiac disease and tic disorders; no significant difference in IgA deficiency was observed between female cohorts. Pediatric OCD subjects also displayed significantly lower adjusted serum IgA levels than the ASD and anxiety disorder cohorts. Adults with OCD were also significantly less likely than children with OCD to display IgA deficiency (OR = 2.71; 95% CI = 1.71-4.28). When compared with children with celiac disease, no significant difference in IgA levels or rates of IgA deficiency were observed in the pediatric OCD cohort. We provide further evidence of IgA abnormalities in pediatric-onset OCD. These results require further investigation to determine if these abnormalities impact the clinical course of OCD in children.
Topics: Adolescent; Age Factors; Celiac Disease; Child; Cohort Studies; Dysgammaglobulinemia; Female; Humans; Immunoglobulin A; Male; Mental Disorders; Obsessive-Compulsive Disorder; Retrospective Studies; Sex Factors
PubMed: 30892924
DOI: 10.1089/cap.2018.0043 -
Nutrients Sep 2015In the present narrative review, we analyzed the relationship between seronegative celiac disease (SNCD) and immunoglobulin deficiencies. For this purpose, we conducted... (Review)
Review
In the present narrative review, we analyzed the relationship between seronegative celiac disease (SNCD) and immunoglobulin deficiencies. For this purpose, we conducted a literature search on the main medical databases. SNCD poses a diagnostic dilemma. Villous blunting, intraepithelial lymphocytes (IELs) count and gluten "challenge" are the most reliable markers. Immunohistochemistry/immunofluorescence tissue transglutaminase (tTG)-targeted mucosal immunoglobulin A (IgA) immune complexes in the intestinal mucosa of SNCD patients may be useful. In our experience, tTG-mRNA was similarly increased in seropositive celiac disease (CD) and suspected SNCD, and strongly correlated with the IELs count. This increase is found even in the IELs' range of 15-25/100 enterocytes, suggesting that there may be a "grey zone" of gluten-related disorders. An immune deregulation (severely lacking B-cell differentiation) underlies the association of SNCD with immunoglobulin deficiencies. Therefore, CD may be linked to autoimmune disorders and immune deficits (common variable immunodeficiency (CVID)/IgA selective deficiency). CVID is a heterogeneous group of antibodies dysfunction, whose association with CD is demonstrated only by the response to a gluten-free diet (GFD). We hypothesized a familial inheritance between CD and CVID. Selective IgA deficiency, commonly associated with CD, accounts for IgA-tTG seronegativity. Selective IgM deficiency (sIgMD) is rare (<300 cases) and associated to CD in 5% of cases. We diagnosed SNCD in a patient affected by sIgMD using the tTG-mRNA assay. One-year GFD induced IgM restoration. This evidence, supporting a link between SNCD and immunoglobulin deficiencies, suggests that we should take a closer look at this association.
Topics: Animals; Autoantibodies; Biomarkers; Celiac Disease; Common Variable Immunodeficiency; Diagnosis, Differential; Diet, Gluten-Free; Humans; IgA Deficiency; Immunoglobulins; Intestines; Predictive Value of Tests; Serologic Tests
PubMed: 26371035
DOI: 10.3390/nu7095350 -
Annals of Allergy, Asthma & Immunology... Aug 2020Serum immunoglobulin G (IgG) concentrations are integral to the workup of immune deficiencies and IgG4-related disease (IgG4-RD). Demographic differences in IgG...
BACKGROUND
Serum immunoglobulin G (IgG) concentrations are integral to the workup of immune deficiencies and IgG4-related disease (IgG4-RD). Demographic differences in IgG concentrations are poorly described but can influence test interpretation, contribute to racial disparities in primary immunodeficiency diagnosis, and explain demographic differences in IgG concentrations in IgG4-RD.
OBJECTIVE
To assess differences in IgG and IgG subclass concentrations according to sex and race.
METHODS
We identified patients with IgG and IgG subclass concentrations measured in a large health care system. Multivariate-adjusted differences in IgG and IgG subclass concentrations and the proportion of subjects with results outside of reference ranges according to sex and race were estimated.
RESULTS
Of the 12,851 patients, the mean age was 54.7 years and 7917 (62%) were female. Of these, 11,673 (91%) were white, 611 (5%) were black, and 302 (2%) were Asian. Compared with the mean concentrations of white patients, Asian and black patients had higher mean concentrations of IgG (1340.0 and 1504.4 vs 988.1 mg/dL, P < .001), IgG1 (782.0 and 938.4 vs 592.4 mg/dL, P < .001), IgG2 (493.5 and 384.2 vs 305 mg/dL, P < .001), IgG3 (76.6 and 91.9 vs 55.9 mg/dL, P < .001), and IgG4 (140.4 and 53.6 vs 41.6 mg/dL, P < .001). Immunoglobin G subclass 4 concentrations were higher in males than those in females (56.3 vs 37.4 mg/dL, P < .001). Similar observations were made when comparing the proportions of patients with results outside of reference ranges and after stratifying by diagnosis.
CONCLUSION
Immunoglobin G and IgG subclass concentrations differ according to sex and race. These findings may have implications for the interpretation of these test results but require confirmation in diverse, healthy populations.
Topics: Adult; Aged; Aged, 80 and over; Cohort Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; IgG Deficiency; Immunoglobulin G; Immunoglobulin G4-Related Disease; Immunoglobulin Isotypes; Male; Middle Aged; Race Factors; Sex Factors
PubMed: 32224206
DOI: 10.1016/j.anai.2020.03.018 -
JPMA. the Journal of the Pakistan... May 2022Berardinelli Seip Congenital Lipodystrophy (BSCL) or Congenital Generalized Lipodystrophy (CGL) is one of the four subgroups of lipodystrophy syndrome which is...
Berardinelli Seip Congenital Lipodystrophy (BSCL) or Congenital Generalized Lipodystrophy (CGL) is one of the four subgroups of lipodystrophy syndrome which is characterized by varying degrees of loss of adipose mass in the body. It is an extremely rare autosomal recessive disorder and commonly reported clinical presentations include muscular hypertrophy, gigantism, hepatomegaly, impaired glucose tolerance, acanthosis nigricans, hypertriglyceridaemia, cardiomyopathy, intellectual impairment, bone cysts and phlebomegaly. We present a case of a 4.5 years old male child born to consanguineous parents, presented with pneumonia. There was history of recurrent diarrhea and chest infection in the past. He had acromegaly like features, hirsutism, firm hepatomegaly, a well defined bone cyst in proximal right femur, pancytopenias with normal bone marrow biopsy report, hypertriglyceridemia and selective IgA deficiency. This is the first case of BSCL, reported in Pakistan with a bone cyst and IgA deficiency. Such patients need to be identified and monitored for complications like diabetes mellitus and hypertrophic cardiomyopathy.
Topics: Bone Cysts; Child, Preschool; Hepatomegaly; Humans; IgA Deficiency; Lipodystrophy; Lipodystrophy, Congenital Generalized; Male
PubMed: 35713067
DOI: 10.47391/JPMA.3182