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BMC Pediatrics Nov 2022X-linked hyper-immunoglobulin M (XHIGM), a primary immunodeficiency syndrome caused by mutations in the CD40 ligand gene(CD40LG), presents with recurrent respiratory...
BACKGROUND
X-linked hyper-immunoglobulin M (XHIGM), a primary immunodeficiency syndrome caused by mutations in the CD40 ligand gene(CD40LG), presents with recurrent respiratory infections in pediatric patients. We aimed to evaluate the spectrum of clinical features and respiratory pathogens in pediatric patients with XHIGM in China.
METHODS
We retrospectively reviewed seven pediatric patients who were diagnosed with XHIGM and received follow-up treatment at the Guangzhou Women and Children's Medical Center between January 2010 and January 2021. We determined their clinical characteristics, causative pathogens, and prognosis by performing peripheral immunological and genetic tests.
RESULTS
There were seven boys with age ranging from 4-20 months (median age, 13 months). Four of the seven respiratory infections were caused by Talaromyces marneffei(T. marneffei). Two patients had viral infections caused by cytomegalovirus (CMV) and human adenovirus respectively. One patient had a mixed infection caused by Pneumocystis carinii and CMV. Except for one child who died of respiratory failure, one patient received hematopoietic stem cell transplantation (HSCT) and recovered well, the other five patients survived with regular infusions of intravenous immunoglobulin (IVIg) during the follow-up period. Six patients had reduced antibody levels, especially IgG, IgA, and IgE levels. Increased serum IgM levels were detected in four cases, and three cases presented normal IgM levels at onset. All children were diagnosed with XHIGM with CD40LG variation. Three novel mutations were identified in the present study.
CONCLUSIONS
Our study suggests that respiratory infections usually begin within 2 years old, fungi and viruses are important pathogens causing respiratory infections in children with XHIGM. In endemic areas, T. marneffei is the common pathogen of respiratory tract infection in children with the disease.
Topics: Male; Humans; Female; Child; Infant; Child, Preschool; CD40 Ligand; Hyper-IgM Immunodeficiency Syndrome; Retrospective Studies; Respiratory Tract Infections; Mutation; China; Immunoglobulin M; Cytomegalovirus Infections
PubMed: 36419145
DOI: 10.1186/s12887-022-03726-z -
Colombia Medica (Cali, Colombia) 2022Inborn errors of immunity, mainly Predominantly Antibody deficiencies with normal IgG levels are unrecognized in adults with lung diseases such as bronchiectasis or...
BACKGROUND
Inborn errors of immunity, mainly Predominantly Antibody deficiencies with normal IgG levels are unrecognized in adults with lung diseases such as bronchiectasis or recurrent pneumonia.
OBJECTIVE
To determine IgM, IgA, IgG2 subclass deficiencies, and Specific antibody deficiency (anti-pneumococcal polysaccharide antibodies) in adults with non-cystic fibrosis bronchiectasis or recurrent pneumonia.
METHODS
Cross-sectional study. Consecutive patients with non-cystic fibrosis bronchiectasis or recurrent pneumonia were recruited in Cali, Colombia. IgG, IgA, IgM, and IgE, IgG2subclass and IgG anti-pneumococcal serum levels were measured.
RESULTS
Among the 110 participants enrolled, Antibody deficiencies with normal serum IgG levels were found in 11(10%) cases. IgA deficiency (3 cases), IgM deficiency (2 cases) and IgG2 deficiency (2 cases) were the most frequent primary immunodeficiencies. In addition, IgG2+IgA deficiency, Ataxia-telangiectasia, Hyper-IgE syndrome and Specific Antibody Deficiency(anti-polysaccharides) were found in one case each.
CONCLUSIONS
Predominantly antibody deficiencies with normal IgG levels are an important etiology of non-cystic fibrosis bronchiectasis and recurrent pneumonia in adults.
Topics: Adult; Humans; Cross-Sectional Studies; IgA Deficiency; IgG Deficiency; Pneumonia; Bronchiectasis; Immunoglobulin G; Immunologic Deficiency Syndromes; Immunoglobulin M; Immunoglobulin A; Fibrosis
PubMed: 36415694
DOI: 10.25100/cm.v53i2.4832 -
PloS One 2022The aim of this study was to estimate the prevalence of selective immunoglobulin A deficiency (SIgAD) among children with type 1 diabetes mellitus (DM) in Ternopil...
The aim of this study was to estimate the prevalence of selective immunoglobulin A deficiency (SIgAD) among children with type 1 diabetes mellitus (DM) in Ternopil region (western Ukraine). Serum IgA levels were measured in 240 patients aged 4-17 years with DM and in 324 children of a control group of the same age. Normal IgA level was observed in 210 (87.5%) patients, increased-in 18 (7.5%), decreased (lower than the age reference value)-in 12 (5.0%) patients with DM. The mean IgA level in patients with DM was 152.11±73.78 mg/dL. SIgAD criteria were met by 7 (2.9%) children with DM, but none of the children of the control group met the SIgAD criteria. Female / male ratio among the patients with SIgAD was 1/6. There was no history of recurrent infections in these patients. No correlation between IgA and HbA1c levels was detected. Autoimmune thyroiditis was observed in 42.9% of patients with DM and SIgAD, and in 3.5% of patients with DM and normal or increased IgA levels. Thus, the prevalence of selective IgA deficiency in children with DM in Ternopil region (Ukraine) is 2.9% (1:34). This study shows that patients with low IgA levels need further re-examination of IgA levels to exclude SIgAD. Children with SIgAD and DM should be monitored for autoimmune manifestations that may affect the course and consequences of the disease.
Topics: Child; Humans; Male; Female; IgA Deficiency; Ukraine; Diabetes Mellitus, Type 1; Immunoglobulin A
PubMed: 36395204
DOI: 10.1371/journal.pone.0277273 -
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... Aug 2022The majority of primary immunodeficiencies (PIDs) are antibody deficiencies (PADs), and not all of them are rare diseases; As an example, Caucasian individuals suffer...
The majority of primary immunodeficiencies (PIDs) are antibody deficiencies (PADs), and not all of them are rare diseases; As an example, Caucasian individuals suffer from selective IgA deficiency at a frequency of 1:500. In addition to infections, symptomatic patients with PAD are more likely to develop neoplastic, autoimmune, and allergic diseases. In the event that PAD is neglected or delayed for more than ten years, complications develop, eventually resulting in death. No studies have been conducted to devise and report detailed ready-to-use protocols for managing PAD to date. This study aimed to propose protocols and guidelines for the adult PAD patients' standard care. Preparing the protocol, we considered the frequency and type of laboratory tests, imaging, endoscopic examinations, specialist consultations, and standardized recommendations for further care in the place of residence. As a result of the proposed monitoring scheme, patients can be provided with complete care in terms of their underlying conditions and comorbidities, as well as early detection of complications. This protocol will serve as a guide for physicians dealing with these patients and enable comparisons of patient groups across a variety of treatment centers, even far away from each other. A national consultant in the field of clinical immunology verified the protocol mainly developed by Polish experts from reference immunology centres for adults.
Topics: Adult; Comorbidity; Humans; IgA Deficiency; Primary Immunodeficiency Diseases; Quality of Life; Standard of Care
PubMed: 36243926
DOI: 10.18502/ijaai.v21i4.10285 -
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 -
Pediatrics and Neonatology Jan 2023IgG subclass deficiency is a laboratory diagnosis and becomes important with recurrent infections. This study aimed to examine the demographic, clinical, and laboratory...
BACKGROUND
IgG subclass deficiency is a laboratory diagnosis and becomes important with recurrent infections. This study aimed to examine the demographic, clinical, and laboratory results of pediatric cases with IgG subclass deficiency and to improve the understanding of the clinical significance of IgG subclass deficiency.
METHODS
In this study, the clinical and laboratory features of 111 pediatric patients, with at least one whose serum IgG subclasses was measured as lower than 2 standard deviation of healthy aged-matched control values, were evaluated. The clinical and laboratory features of the cases with isolated IgG subclass deficiency (Group 1) and those with low serum levels of any of IgG, IgA, and IgM in addition to the IgG subclass deficiency (Group 2) were compared.
RESULTS
A total of 55 (49.54%) and 56 (50.45%) patients were included in Groups 1 and 2, respectively. Among our studied cases, 20 (18.1%) had a history of hospitalization in the neonatal period, 61 (54.95%) had at least one hospitalization due to infection, and 55 (49.54%) had a history of recurrent infection. The frequencies of these three conditions were statistically significantly higher in Group 2 (p < 0.05). The frequencies of infections in the last year in Groups 1 and 2 were 4.4 ± 1.2 and 5.4 ± 1.9, respectively (p < 0.05). As a result of recurrent infections, 43.24% (n = 48) of our patients received antibiotic prophylaxis, and 21.62% (n = 24) had immunoglobulin replacement therapy. Furthermore, the numbers of patients who needed these treatments were higher in Group 2 (p < 0.05).
CONCLUSION
In cases with IgG subclass deficiencies, concomitant main-group immunoglobulin deficiencies may increase the number and severity of infections, leading to hospitalizations, antibiotic prophylaxis, and immunoglobulin therapy. More attention should be paid to cases of immunoglobulin main-group deficiencies in the follow-up of these cases.
Topics: Infant, Newborn; Child; Humans; Aged; Reinfection; IgG Deficiency; Immunoglobulin G; Antibiotic Prophylaxis
PubMed: 36089538
DOI: 10.1016/j.pedneo.2022.04.014 -
Scientific Reports Sep 2022Although some adults infected with influenza 2009 A(H1N1)pdm09 viruses mounted high hemagglutination inhibition (HAI) antibody response, they still suffered from severe...
Although some adults infected with influenza 2009 A(H1N1)pdm09 viruses mounted high hemagglutination inhibition (HAI) antibody response, they still suffered from severe disease, or even death. Here, we analyzed antibody profiles in patients (n = 31, 17-65 years) admitted to intensive care units (ICUs) with lung failure and invasive mechanical ventilation use due to infection with A(H1N1)pdm09 viruses during 2009-2011. We performed a comprehensive analysis of the quality and quantity of antibody responses using HAI, virus neutralization, biolayer interferometry, enzyme-linked-lectin and enzyme-linked immunosorbent assays. At time of the ICU admission, 45% (14/31) of the patients had HAI antibody titers ≥ 80 in the first serum (S1), most (13/14) exhibited narrowly-focused HAI and/or anti-HA-head binding antibodies targeting single epitopes in or around the receptor binding site. In contrast, 42% (13/31) of the patients with HAI titers ≤ 10 in S1 had non-neutralizing anti-HA-stem antibodies against A(H1N1)pdm09 viruses. Only 19% (6/31) of the patients showed HA-specific IgG1-dominant antibody responses. Three of 5 fatal patients possessed highly focused cross-type HAI antibodies targeting the (K130 + Q223)-epitopes with extremely low avidity. Our findings suggest that narrowly-focused low-quality antibody responses targeting specific HA-epitopes may have contributed to severe infection of the lower respiratory tract.
Topics: Adult; Antibodies, Viral; Antibody Formation; Critical Illness; Epitopes; Hemagglutinin Glycoproteins, Influenza Virus; Humans; IgA Deficiency; Influenza A Virus, H1N1 Subtype; Influenza Vaccines; Influenza, Human
PubMed: 36056075
DOI: 10.1038/s41598-022-18977-0 -
Frontiers in Immunology 2022
Topics: Humans; IgA Deficiency; Immunologic Deficiency Syndromes; Primary Immunodeficiency Diseases
PubMed: 36052063
DOI: 10.3389/fimmu.2022.959720 -
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