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Archivum Immunologiae Et Therapiae... Apr 2020We sought to determine whether HLA-A and -B type and haplotype frequencies differ between subgroups of adults with IgG subclass deficiency (IgGSD). We retrospectively...
We sought to determine whether HLA-A and -B type and haplotype frequencies differ between subgroups of adults with IgG subclass deficiency (IgGSD). We retrospectively compared type and haplotype frequencies of three subgroups of 269 unrelated adult IgGSD patients (70 subnormal IgG1; 121 subnormal IgG3; 78 subnormal IgG1/IgG3) and controls (1,321 for types; 751 for haplotypes). We selected types and haplotypes because their uncorrected frequencies differed significantly from controls in a previous adult IgGSD/common variable immunodeficiency cohort: A*24; B*14; B*35; B*40; B*49; B*50; B*58; B*62; A*01,B*08; A*02,B*44; A*02,B*60; A*03,B*07; A*03,B*14; A*03,B*44; A*31,B*40; and A*32,B*14. We used χ analysis (2 × 4 tables) to identify frequency differences across three subgroups and controls. If the null hypothesis was rejected (p < 0.05), we computed 2 × 2 χ tables to compare six combinations of subgroup and control frequencies [Bonferroni p < 0.0083 (< 0.05/6)]. Mean age was 48 ± 13 years; 82.2% were women. B*35 and B*40 frequencies were higher in subnormal IgG1 than subnormal IgG3 patients (0.1000 vs. 0.0248 and 0.0571 vs. 0.0083, respectively; p ≤ 0.0061). B*62 frequencies were lower in three IgGSD subgroups than controls (p < 0.0001, respectively). A*02, B*44 frequency was higher in subnormal IgG1/IgG3 patients than controls (0.1282 vs. 0.0632, respectively; p = 0.0024). A*02, B*60 frequency was lower in subnormal IgG3 patients than controls (0.0 vs. 0.0233, respectively; p = 0.0051). HLA-B*35 and -B*40 frequencies differ significantly between some IgGSD subgroups. B*62, A*02, B*44, and A*02, B*60 frequencies differ significantly between some IgGSD subgroups and controls.
Topics: Adult; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; HLA-A Antigens; HLA-B Antigens; Haplotypes; Humans; IgG Deficiency; Immunoglobulin G; Immunoglobulin Isotypes; Male; Middle Aged; Retrospective Studies
PubMed: 32307610
DOI: 10.1007/s00005-020-00572-8 -
Frontiers in Immunology 2018Patients with primary immunodeficiency can be prone to severe Epstein-Barr virus (EBV) associated immune dysregulation. Individuals with mutations in the... (Review)
Review
Patients with primary immunodeficiency can be prone to severe Epstein-Barr virus (EBV) associated immune dysregulation. Individuals with mutations in the interleukin-2-inducible T-cell kinase () gene experience Hodgkin and non-Hodgkin lymphoma, EBV lymphoproliferative disease, hemophagocytic lymphohistiocytosis, and dysgammaglobulinemia. In this review, we give an update on further reported patients. We believe that current clinical data advocate early definitive treatment by hematopoietic stem cell transplantation, as transplant outcome in primary immunodeficiency disorders in general has gradually improved in recent years. Furthermore, we summarize experimental data in the murine model to provide further insight of pathophysiology in ITK deficiency.
Topics: Adolescent; Animals; Child; Child, Preschool; Disease Models, Animal; Epstein-Barr Virus Infections; Female; Hematopoietic Stem Cell Transplantation; Herpesvirus 4, Human; Hodgkin Disease; Humans; Immunologic Deficiency Syndromes; Infant, Newborn; Lymphoma, Non-Hodgkin; Lymphoproliferative Disorders; Male; Mice; Mice, Knockout; Protein-Tyrosine Kinases; T-Lymphocytes
PubMed: 29867957
DOI: 10.3389/fimmu.2018.00979 -
Journal of Investigational Allergology... 2015X-linked lymphoproliferative syndrome type 2 is a rare hereditary immunodeficiency caused by mutations in the XIAP gene. This immunodeficiency frequently results in...
BACKGROUND
X-linked lymphoproliferative syndrome type 2 is a rare hereditary immunodeficiency caused by mutations in the XIAP gene. This immunodeficiency frequently results in hemophagocytic lymphohistiocytosis, although hypogammaglobulinemia and dysgammaglobulinemia are also common.
OBJECTIVE
We identified 17 patients from 12 Japanese families with mutations in XIAP. The Glu349del mutation was observed in 3 patients, each from a different family. Interestingly, these patients exhibited dysgammaglobulinemia but not hemophagocytic lymphohistiocytosis. We conducted an immunological study of patients carrying Glu349del and other mutations to elucidate the pathogenic mechanisms of dysgammaglobulinemia in patients with mutations in the XIAP gene.
PATIENTS AND METHODS
We performed an immunological study of 2 patients carrying the Glu349del mutation and 8 patients with other mutations.
RESULTS
Flow cytometry showed that the percentage of memory B cells in patients with a mutation in XIAP was lower than that observed in the healthy controls. The patients with the Glu349del mutation had a lower percentage of memory B cells than those with other mutations. Ig production was reduced in patients with the Glu349del mutation. Increased susceptibility to apoptosis was observed in the patients with other mutations. Susceptibility to apoptosis was normal in patients with Glu349del. Microarray analysis indicated that expression of Ig-related genes was reduced in patients with the Glu349del mutation and that the pattern was different from that observed in the healthy controls or patients with other mutations in XIAP.
CONCLUSIONS
Patients carrying the Glu349del mutation in the XIAP gene may have a clinically and immunologically distinct phenotype from patients with other XIAP mutations. The Glu349del mutation may be associated with dysgammaglobulinemia.
Topics: Adolescent; Apoptosis; Asian People; B-Lymphocytes; Case-Control Studies; Cells, Cultured; Child; Child, Preschool; DNA Mutational Analysis; Dysgammaglobulinemia; Female; Flow Cytometry; Gene Expression Profiling; Genetic Diseases, X-Linked; Genetic Predisposition to Disease; Humans; Immunologic Memory; Immunophenotyping; Infant; Japan; Lymphoproliferative Disorders; Male; Mutation; Oligonucleotide Array Sequence Analysis; Pedigree; Phenotype; T-Lymphocytes; X-Linked Inhibitor of Apoptosis Protein
PubMed: 26182687
DOI: No ID Found -
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 -
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 -
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 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 -
Clinical Medicine (London, England) Feb 2018We present the case of a 67-year-old man who suffered an acute anaphylactic reaction during red cell transfusion due to the presence of anti-IgA antibodies. The...
We present the case of a 67-year-old man who suffered an acute anaphylactic reaction during red cell transfusion due to the presence of anti-IgA antibodies. The incidence and clinical relevance of anti-IgA antibodies in IgA deficiency is reviewed, and the wider investigation and management of acute transfusion reactions is also discussed. This case highlights the need to consider the potential risks of blood component transfusion against the purported benefit.
Topics: Aged; Anemia, Pernicious; Antibodies, Anti-Idiotypic; Erythrocyte Transfusion; Humans; IgA Deficiency; Immunoglobulin A; Male; Transfusion Reaction; Treatment Outcome; Vitamin B 12; Vitamin B Complex
PubMed: 29436447
DOI: 10.7861/clinmedicine.18-1-95 -
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