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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 -
Pediatric Critical Care Medicine : a... Sep 2018To present the recommendations and supporting literature for selection and processing of RBC products in critically ill children developed by the Pediatric Critical Care...
OBJECTIVES
To present the recommendations and supporting literature for selection and processing of RBC products in critically ill children developed by the Pediatric Critical Care Transfusion and Anemia Expertise Initiative.
DESIGN
Consensus conference series of international, multidisciplinary experts in RBC transfusion management of critically ill children METHODS:: The panel of 38 experts developed evidence-based, and when evidence was lacking, expert-based clinical recommendations as well as research priorities for RBC transfusions in critically ill children. The RBC processing subgroup included five experts. Electronic searches were conducted using PubMed, EMBASE, and Cochrane Library databases from 1980 to May 2017. Agreement was obtained using the Research and Development/UCLA Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method.
RESULTS
Five recommendations reached agreement (> 80%). Irradiated cellular products are recommended for children at risk of transfusion-associated graft versus host disease due to severe congenital or acquired causes of immune deficiency or when the blood donor is a blood relative. Washed cellular blood components and avoidance of other plasma-containing products are recommended for critically ill children with history of severe allergic reactions or anaphylaxis to blood transfusions, although patient factors appear to be important in the pathogenesis of reactions. For children with history of severe allergic transfusion reactions, evaluation for allergic stigmata prior to transfusion is recommended. In children with severe immunoglobulin A deficiency with evidence of antiimmunoglobulin A antibodies and/or a history of a severe transfusion reaction, immunoglobulin A-deficient blood components obtained either from an immunoglobulin A-deficient donor and/or washed cellular components is recommended.
CONCLUSIONS
The Transfusion and Anemia Expertise Initiative consensus conference developed recommendations for selection and processing of RBC units for critically ill children. Recommendations in this area are largely based on pediatric and adult case report data.
Topics: Anemia; Child; Critical Care; Critical Illness; Erythrocyte Transfusion; Evidence-Based Medicine; Graft vs Host Disease; Humans; IgA Deficiency; Intensive Care Units, Pediatric; Transfusion Reaction
PubMed: 30161072
DOI: 10.1097/PCC.0000000000001625 -
Journal of Gastroenterology and... Jan 2016Multiple European studies report increased prevalence of selective immunoglobulin A deficiency (SIgAD) and partial immunoglobulin A deficiency (PIgAD) in patients with...
BACKGROUND AND AIMS
Multiple European studies report increased prevalence of selective immunoglobulin A deficiency (SIgAD) and partial immunoglobulin A deficiency (PIgAD) in patients with celiac disease (CD). However; prospective data representing North American adults are lacking. While SIgAD precludes the use of IgA-tissue-transglutaminase antibody (IgA-tTG), the effect of PIgAD on IgA-tTG sensitivity is not well documented. We aim to determine the prevalence and impact of IgA deficiency on CD presentation and diagnosis in North American adult patients.
METHODS
We reviewed 1000 consecutive patients undergoing IgA-tTG testing and 243 healthy controls. Eligible sera were tested for IgA-tTG, serum immunoglobulins, and IgA/IgG-deamidated gliadin peptide (IgA/IgG-DGP).
RESULTS
Prevalence of SIgAD was marginally higher in patients with CD (1.9%) compared with healthy controls (0.4%, P = 0.24) and patients without CD (0.7%, P = 0.173). Prevalence of PIGAD was similar in patients with CD (4.8%) compared with healthy controls (5.9%, P = 0.57) and patients without CD (7.2%, P = 0.22). One (16.7%) of 6 patients with CD with SIgAD and all 15 (100%) with PIGAD tested IgA-tTG positive prior to gluten-free diet initiation. Patients with CD with SIGAD showed lower frequency of gastrointestinal symptoms (33% vs 82%, P = 0.01) and more co-morbid autoimmune disease (67% vs 23%, P = 0.03) when compared with patients with CD with normal IgA.
CONCLUSIONS
The prevalence of SIgAD in North American patients with CD is comparable with European data but not significantly different than control populations. Patients with CD with SIgAD exhibit decreased IgA-tTG sensitivity and lack of gastrointestinal symptoms. PIgAD is common in patients with gastrointestinal disorders but does not alter CD presentation or IgA-tTG sensitivity.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Celiac Disease; Female; Humans; IgA Deficiency; Immunoglobulin A; Male; Middle Aged; Prevalence; Retrospective Studies; Sensitivity and Specificity; Transglutaminases; United States; Young Adult
PubMed: 26412412
DOI: 10.1111/jgh.13176 -
Immunology Nov 2015The composition of the microbiome in health and disease has only recently become a major research focus. Although it is clear that an imbalance or dysbiosis in the... (Review)
Review
The composition of the microbiome in health and disease has only recently become a major research focus. Although it is clear that an imbalance or dysbiosis in the microbiota is associated with disease, its interrelatedness to disease penetrance is largely unknown. Inflammatory bowel disease (IBD) is an excellent disease in which to explore these questions because of the extensive genetic studies identifying disease susceptibility loci and the ability to easily sample the intestinal microbiota in IBD patients due to the accessibility of stool samples. In addition, mouse models of IBD have contributed to our understanding of the interrelatedness of the gut microbiota and genes associated with IBD. The power of the mouse studies is that multiple colitis models exist that can be used in combination with genetically modified mice that harbour deficiencies in IBD susceptibility genes. Collectively, these studies revealed that bacterial dysbiosis does occur in human IBD and in mouse colitis models. In addition, with an emphasis on immune genes, the mouse studies provided evidence that specific immune regulatory proteins associated with IBD influence the gut microbiota in a manner consistent with disease penetrance. In this review, we will discuss studies in both humans and mice that demonstrate the impact of immunodeficiences in interleukin-10, interleukin-17, nucleotide-binding oligomerization domain (NOD) 2, NOD-like receptor proteins 3 and 6, Toll-like receptor or IgA have on the interrelatedness between the composition of the gut microbiota and disease penetrance of IBD and its mouse models.
Topics: Animals; Colitis; Disease Models, Animal; Dysbiosis; Gastrointestinal Microbiome; Humans; IgA Deficiency; Immunologic Deficiency Syndromes; Inflammatory Bowel Diseases; Interleukin-10; Mice; Models, Immunological; Nod Signaling Adaptor Proteins; Penetrance; Th17 Cells; Toll-Like Receptors
PubMed: 26211540
DOI: 10.1111/imm.12511 -
Allergy and Asthma Proceedings 2015Selective immunoglobulin E (IgE) deficiency (IgED) is defined as serum levels of IgE more than or equal to 2 kIU/L and is associated with immune dysregulation and...
Selective immunoglobulin E (IgE) deficiency (IgED) is defined as serum levels of IgE more than or equal to 2 kIU/L and is associated with immune dysregulation and autoimmunity. This study aimed to investigate a prevalence of atherosclerotic cardiovascular disease (ASCVD) in population with IgED. Within the electronic patient record (EPR) database of Leumit Health Care Services (LHS) in Israel, data capture was performed using IBM Cognos 10.1.1 BI Report Studio software. The case samples were drawn from the full study population (n = 18,487), having any allergy-related symptoms and/or those requesting antiallergy medications and performed serum total IgE measurement during 2012 at LHS. All subjects aged more than or equal to 40 years old, with serum total IgE less than 2 kIU/L were included in case group. Control group was randomly sampled from the remained subjects, with a case-control ratio of 10 controls for each case (1:10). The comorbid cardiovascular diseases during less than or equal to 10 years before serum total IgE testing were identified and retrieved using specific International Classification of Diseases, 9th Revision, Clinical Modification diagnostic codes. There were 103 in case and 1030 subjects in control group. Compared with control group patients, the case group had significantly more arterial hypertension [34 (37.7%) versus 187 (18.2%), p < 0.001], ischemic heart disease (IHD) [26 (25.2%) versus 87 (8.4%), p < 0.001], carotid stenosis [5 (4.9%) versus 7 (0.7%), p = 0.003], cerebrovascular disease (CVD) [3 (2.9%) versus 5 (0.5%), p = 0.029], and peripheral vascular disease (PVD) [4 (3.9%) versus 9 (0.9%), p = 0.024]. IgED is associated with higher prevalence of arterial hypertension and ASCVD.
Topics: Adolescent; Adult; Aged; Cardiovascular Diseases; Case-Control Studies; Child; Child, Preschool; Databases, Factual; Dysgammaglobulinemia; Female; Humans; Immunoglobulin E; Israel; Male; Middle Aged; Prevalence; Risk Factors; Young Adult
PubMed: 25976439
DOI: 10.2500/aap.2015.36.3825 -
Journal of Clinical Immunology May 2018
Review
Topics: Biomarkers; Biopsy; DNA Mutational Analysis; Humans; Hyper-IgM Immunodeficiency Syndrome, Type 1; Male; Middle Aged; Phenotype; Skin; Warts
PubMed: 29730845
DOI: 10.1007/s10875-018-0505-z -
International Journal of Environmental... Aug 2018: Imunoglobulin A (IgA) deficiency (IgAD) is the most common form of primary immunodeficiency in Western countries. There have been several reports on IgAD complicated...
: Imunoglobulin A (IgA) deficiency (IgAD) is the most common form of primary immunodeficiency in Western countries. There have been several reports on IgAD complicated by glomerulonephritis in adults, but only very few cases of IgAD with nephropathy have been reported in children. We present two cases of IgAD with relapsing nephrotic syndrome in pediatric age. : A 4-year-old boy and a 2-year-old boy presented with bilateral periorbital oedema and weight gain. The results of laboratory tests revealed IgAD (IgA < 7 mg/dL), normal creatinine, hypoprotidaemia, hypoalbuminaemia, and nephrotic proteinuria. A diagnosis of IgAD and idiopathic nephrotic syndrome was made, and steroid treatment (prednisone 60 mg/mq/day) was started. During steroid tapering, the children experienced several relapses and to obtain a positive outcome they required therapy with human monoclonal anti-CD20 antibodies (rituximab in the first child, ofatumumab in the second one). : Our cases highlight that IgAD can be observed in nephrotic syndrome and nephropathy in children with IgAD appears to be complicated and difficult to treat with corticosteroids alone. Further research is needed to better describe the clinical manifestations and pathological pictures among subjects with IgAD and nephrotic syndrome to understand whether IgAD has a prognostic value in children with nephrotic syndrome and to let clinical physicians define a more personalized and appropriate approach for the management of these patients.
Topics: Adrenal Cortex Hormones; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Child, Preschool; Humans; IgA Deficiency; Immunosuppressive Agents; Male; Nephrotic Syndrome; Proteinuria; Recurrence; Rituximab
PubMed: 30096909
DOI: 10.3390/ijerph15081702 -
Genes Oct 2022Background: Inborn errors of immunity (IEIs) are comprised of heterogeneous groups of genetic disorders affecting immune function. In this report, a 17-month-old Malay...
Background: Inborn errors of immunity (IEIs) are comprised of heterogeneous groups of genetic disorders affecting immune function. In this report, a 17-month-old Malay patient suspected of having Hyper IgM syndrome, a type of IEIs, was described. However, the diagnosis of Hyper IgM syndrome was excluded by the normal functional studies and the mild features of ectodermal dysplasia observed from a further clinical phenotype inspection. Methods: Whole-exome sequencing (WES) was performed to unravel the causative mutation in this patient. Results: The variant analysis demonstrated a novel missense mutation in NFKBIA (NM_020529:c.94A > T,NP_065390:p.Ser32Cys) and was predicted as damaging by in silico prediction tools. The NFKBIA gene encodes for IκBα, a member of nuclear factor kappa B (NF-κB) inhibitors, playing an important role in regulating NF-κB activity. The mutation occurred at the six degrons (Asp31-Ser36) in IκBα which were evolutionarily conserved across several species. Prediction analysis suggested that the substitution of Ser32Cys may cause a loss of the phosphorylation site at residue 32 and a gain of the sumoylation site at residue 38, resulting in the alteration of post-translational modifications of IκBα required for NF-κB activation. Conclusion: Our analysis hints that the post-translational modification in the NFKBIA Ser32Cys mutant would alter the signaling pathway of NF-κB. Our findings support the usefulness of WES in diagnosing IEIs and suggest the role of post-translational modification of IκBα.
Topics: Humans; NF-KappaB Inhibitor alpha; NF-kappa B; Mutation, Missense; Hyper-IgM Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Ectodermal Dysplasia; I-kappa B Proteins; Dysgammaglobulinemia
PubMed: 36292785
DOI: 10.3390/genes13101900 -
Iranian Journal of Allergy, Asthma, and... Dec 2021Respiratory diseases are considered as significant causes of morbidity and mortality in primary immunodeficiencies. This study aimed to reveal the radiologic patterns of...
Respiratory diseases are considered as significant causes of morbidity and mortality in primary immunodeficiencies. This study aimed to reveal the radiologic patterns of thoracic involvement in these disorders. A total of 58 patients, including 38 cases with combined cellular-humoral and 20 cases with humoral immunodeficiencies, were enrolled in this study. The "combined" group consisted of 12 cases with severe combined immunodeficiency (SCID) and 26 cases with combined immunodeficiency. The "humoral" group included seven patients with Hyper IgM syndrome (HIGMs), seven cases with common variable immunodeficiency (CVID), three patients with X-linked agammaglobulinemia, and three patients with other types of humoral primary immunodeficiencies (PIDs). The mean age of patients at the time of evaluation was 3.3±3.8 and 5.3±3.9 years in combined and humoral groups, respectively. The findings of chest X-rays and CT scans were interpreted and compared. There was a significant difference for alveolar opacification between combined and humoral immunodeficiencies (58% vs. 30%). The bronchopneumonia-like pattern was detected as a significant finding in patients with SCID (42%) and HIGMs (43%). Atrophy of the thymus was detected significantly often in cases of SCID (67%). Two patients with CVID and lipopolysaccharide-responsive and beige-like anchor protein deficiency showed parenchymal changes of granulomatous lymphocytic interstitial lung disease. No significant difference was detected for bronchiectasis, bronchitis/bronchiolitis patterns, pleural effusion, and thoracic lymphadenopathy. Distinct subtypes of primary immunodeficiency may provoke differing and comparable radiological patterns of thoracic involvement; which can clue the clinician and radiologist to the diagnosis of the disease.
Topics: Agammaglobulinemia; Child; Child, Preschool; Common Variable Immunodeficiency; Diagnosis, Differential; Early Diagnosis; Female; Genetic Diseases, X-Linked; Humans; Hyper-IgM Immunodeficiency Syndrome; Infant; Lung; Male; Retrospective Studies; Severe Combined Immunodeficiency; Tomography, X-Ray Computed
PubMed: 34920652
DOI: 10.18502/ijaai.v20i6.8020 -
Scandinavian Journal of Immunology Nov 2022Isotype class-switch recombination (CSR), somatic hypermutation (SHM), B cell signalling and DNA repair mechanisms defects are responsible for high IgM. The...
Isotype class-switch recombination (CSR), somatic hypermutation (SHM), B cell signalling and DNA repair mechanisms defects are responsible for high IgM. The hyperimmunoglobulin M (HIGM) phenotype and CSR-related defects are now classified under primary antibody defects, combined immunodeficiencies or syndromic immunodeficiencies groups. The aim of the study is to evaluate the diverse phenotypic/genotypic/laboratory characteristics and outcome of patients with CSR defects and HIGM-related defects. We enrolled 50 patients. The most common gene defect was Activation-induced cytidine deaminase (AID) deficiency (n = 18), followed by CD40 Ligand (CD40L) (n = 14) and CD40 (n = 3) deficiency. Median ages at first symptom and diagnosis were significantly lower in CD40L deficiency (8.5 and 30 months, respectively) than AID deficiency (30 and 114 months, respectively) (p = .001 and p = .008, respectively). Frequent clinical symptoms were recurrent (66%) and severe (14.9%) infections, and/or autoimmune/non-infectious inflammatory features (48.4%). Eosinophilia and neutropenia were at a higher rate in CD40L deficiency patients (77.8%, p = .002 and 77.8%, p = .002, respectively) when compared to AID deficiency. Median serum IgM level was low in 28.6% of CD40L deficiency patients. It was significantly lower when compared to AID deficiency (p < 0.001). Six patients (CD40L deficiency n = 4, CD40 deficiency n = 2) underwent hematopoietic stem cell transplantation. Five were alive at the last visit. Four patients two patients with CD40L deficiency, one with CD40 deficiency and one with AID deficiency had novel mutations. In conclusion; patients with CSR defects and HIGM phenotype may present with a wide range of clinical manifestations and laboratory findings. Low IgM, neutropenia and eosinophilia were prominent in patients with CD40L deficiency. Characterization of genetic defect-specific clinical and laboratory features may ease the diagnosis, prevent the underdiagnoses of patients and ameliorate the outcome.
Topics: Humans; CD40 Ligand; Immunoglobulin Class Switching; Hyper-IgM Immunodeficiency Syndrome; Immunoglobulin M; Neutropenia; Cytidine Deaminase
PubMed: 36808635
DOI: 10.1111/sji.13213