scholarly journals Autoimmune Cytopenias and Dysregulated Immunophenotype Act as Warning Signs of Inborn Errors of Immunity: Results From a Prospective Study

2022 ◽  
Vol 12 ◽  
Author(s):  
Ebe Schiavo ◽  
Beatrice Martini ◽  
Enrico Attardi ◽  
Filippo Consonni ◽  
Sara Ciullini Mannurita ◽  
...  
Keyword(s):  
Wide Spectrum ◽  
Genetic Disorders ◽  
Clinical Manifestations ◽  
Warning Signs ◽  
Inborn Errors ◽  
Multiparametric Flow Cytometry ◽  
First Line Therapy ◽  
Inborn Errors Of Immunity ◽  
Autoimmune Cytopenias ◽  
A Prospective Study

Inborn errors of immunity (IEI) are genetic disorders characterized by a wide spectrum of clinical manifestations, ranging from increased susceptibility to infections to significant immune dysregulation. Among these, primary immune regulatory disorders (PIRDs) are mainly presenting with autoimmune manifestations, and autoimmune cytopenias (AICs) can be the first clinical sign. Significantly, AICs in patients with IEI often fail to respond to first-line therapy. In pediatric patients, autoimmune cytopenias can be red flags for IEI. However, for these cases precise indicators or parameters useful to suspect and screen for a hidden congenital immune defect are lacking. Therefore, we focused on chronic/refractory AIC patients to perform an extensive clinical evaluation and multiparametric flow cytometry analysis to select patients in whom PIRD was strongly suspected as candidates for genetic analysis. Key IEI-associated alterations causative of STAT3 GOF disease, IKAROS haploinsufficiency, activated PI3Kδ syndrome (APDS), Kabuki syndrome and autoimmune lymphoproliferative syndrome (ALPS) were identified. In this scenario, a dysregulated immunophenotype acted as a potential screening tool for an early IEI diagnosis, pivotal for appropriate clinical management and for the identification of new therapeutic targets.

scholarly journals Clinical and Genetic Spectrum of Inborn Errors of Immunity in a Tertiary Care Center in Southern India

2021 ◽  
Author(s):  
Harsha Prasada Lashkari ◽  
Manisha Madkaikar ◽  
Aparna Dalvi ◽  
Maya Gupta ◽  
Jacinta Bustamante ◽  
...  
Keyword(s):  
Tertiary Care Hospital ◽  
Care Center ◽  
Tertiary Care ◽  
Clinical Manifestations ◽  
Warning Signs ◽  
Southern India ◽  
Care Hospital ◽  
Optimal Care ◽  
Inborn Errors ◽  
Inborn Errors Of Immunity

Abstract Objectives To study the incidence, clinical manifestations, and genetic spectrum of primary immunodeficiency diseases (PID)/inborn errors of immunity (IEI) in a tertiary care hospital in Southern India. Methods A retrospective analysis of all patients with a clinical suspicion of PID/IEI seen at a tertiary care hospital was performed. All patients had at least one or more warning signs of PID. Serum immunoglobulin levels and other targeted investigations were performed as warranted by the clinical presentation. All families with suspected PID were counseled and offered genetic testing. Results A total of 225 children were evaluated for PID during the study period of 6 y. Fifty-six of them did not meet the European Society of Immunodeficiencies (ESID) criteria (working definition of clinical diagnosis) and were excluded. An IEI was found in 30/49 (61.2%) patients. The most frequent reason for referral was recurrent/unusual or serious infections (28%), or cytopenia (16%). Group IV diseases of immune dysregulation was the most common category (19%), followed by group III predominant antibody deficiencies in 23/163 (14%), as per the International Union of Immunological Societies (IUIS) classification. Conclusions This study highlights the heterogeneity of the present cohort, the underuse of genetic tests, and efforts to provide optimal care for children with possible IEI in this center.

scholarly journals Gut Microbiota–Host Interactions in Inborn Errors of Immunity

2021 ◽  
Vol 22 (3) ◽  
pp. 1416
Author(s):  
Riccardo Castagnoli ◽  
Francesca Pala ◽  
Marita Bosticardo ◽  
Amelia Licari ◽  
Ottavia M. Delmonte ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Wide Spectrum ◽  
Adaptive Immune System ◽  
Clinical Feature ◽  
Inborn Errors ◽  
Mucosal Permeability ◽  
Microbial Dysbiosis ◽  
Inborn Errors Of Immunity ◽  
Key Aspects ◽  
And Function

Inborn errors of immunity (IEI) are a group of disorders that are mostly caused by genetic mutations affecting immune host defense and immune regulation. Although IEI present with a wide spectrum of clinical features, in about one third of them various degrees of gastrointestinal (GI) involvement have been described and for some IEI the GI manifestations represent the main and peculiar clinical feature. The microbiome plays critical roles in the education and function of the host’s innate and adaptive immune system, and imbalances in microbiota-immunity interactions can contribute to intestinal pathogenesis. Microbial dysbiosis combined to the impairment of immunosurveillance and immune dysfunction in IEI, may favor mucosal permeability and lead to inflammation. Here we review how immune homeostasis between commensals and the host is established in the gut, and how these mechanisms can be disrupted in the context of primary immunodeficiencies. Additionally, we highlight key aspects of the first studies on gut microbiome in patients affected by IEI and discuss how gut microbiome could be harnessed as a therapeutic approach in these diseases.

scholarly journals Expanding the potential genes of inborn errors of immunity through protein interactions

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Humza A. Khan ◽  
Manish J. Butte
Keyword(s):  
Genetic Variation ◽  
Protein Interactions ◽  
Immune Cell ◽  
Genetic Disorders ◽  
Cell Types ◽  
Protein Protein Interactions ◽  
Inborn Errors ◽  
Post Translational Modifications ◽  
New Genes ◽  
Inborn Errors Of Immunity

Abstract Background Inborn errors of immunity (IEI) are a group of genetic disorders that impair the immune system, with over 400 genes described so far, and hundreds more to be discovered. To facilitate the search for new genes, we need a way to prioritize among all the genes in the genome those most likely to play an important role in immunity. Results Here we identify a new list of genes by linking known IEI genes to new ones by using open-source databases of protein-protein interactions, post-translational modifications, and transcriptional regulation. We analyze this new set of 2,530 IEI-related genes for their tolerance of genetic variation and by their expression levels in various immune cell types. Conclusions By merging genes derived from protein interactions of known IEI genes with transcriptional data, we offer a new list of candidate genes that may play a role in as-yet undiscovered IEIs.

The Origins of the First Reported Cases of the Primary Immunodeficiency Diseases

2021 ◽  
Author(s):  
Seyed Erfan Rasouli ◽  
Parisa Amirifar
Keyword(s):  
Primary Immunodeficiency ◽  
Case Reports ◽  
Genetic Disorders ◽  
Genetic Defect ◽  
Inborn Errors ◽  
Future Studies ◽  
Inborn Errors Of Immunity ◽  
First Case ◽  
Geographical Dispersion ◽  
First Time

Background: Inborn Errors of Immunity (IEI) or Primary Immunodeficiency Disorders (PID), are heterogeneous diseases with defects on the components of the immune system. We have provided information about the consanguinity and origins of over 400 affected patients for the first time. Methods: To study the genes, we used the classification tables provided by the IUIS (the International Union of Immunological Societies) in 2020, that documents the key clinical and laboratory features of more than 400 inborn errors of immunity. Results: We have identified the national origins of 301 cases with a known gene, while national origins’ information of the 90 other genes (90 cases) was left incomplete, due to the unavailability of the first case reports or the fail to mention the patients’ origin in the article publication of the first report. Among the 301 genes, Asia has the largest geographical dispersion with 103 reported cases. We found that the 101 first case reports, were identified in more than one patient, regardless of the geography they live in. Our survey demonstrated that out of the 165 first reported cases with genetic defects resulted from a consanguineous marriage, 112 cases were identified in Asia. Conclusions: This report provides valuable information on the geographical data and the prevalence of the various genetic disorders, worldwide. Also, by providing information related to parental consanguinity of the first reported cases with a genetic defect, valuable information about inborn errors of immunity, will be accessible for the researchers, which can be used effectively in future studies.

scholarly journals Clinico-laboratory profile of dengue fever in children

2018 ◽  
Vol 6 (1) ◽  
pp. 200
Author(s):  
Gowhar Wani ◽  
Ayesha Imran
Keyword(s):  
Clinical Features ◽  
Clinical Manifestations ◽  
Warning Signs ◽  
Control Measures ◽  
Dengue Case ◽  
Age Group ◽  
Laboratory Findings ◽  
Community Awareness ◽  
Laboratory Profile ◽  
A Prospective Study

Background: Dengue is rising globally. It presents with varied clinical manifestations. This study was done to describe the salient clinical as well as laboratory findings of serologically confirmed cases of dengue fever.Methods: This was a prospective study conducted at Government Multispeciality Hospital-16 Chandigarh from July 2017 to December 2017. All children below 17 years of age that had clinical features of dengue and who were antigen or antibody positive were included in this study.Results: Age group most commonly affected was 5-10 years with maximum number of dengue cases with warning signs(72.94%). Fever was present in all cases followed by headache(89.41%) and myalgia(78.82%). Thrombocytopenia was the commonest hematological abnormality(97.6%).Conclusions: Dengue presents with varied clinical features. Community awareness, early diagnosis and management and vector control measures needs to be strengthened in order to reduce the increasing number of dengue case.

scholarly journals Expanding the Potential Genes of Inborn Errors of Immunity through Protein Interactions

2021 ◽  
Author(s):  
Humza A Khan ◽  
Manish J Butte
Keyword(s):  
Genetic Variation ◽  
Protein Interactions ◽  
Immune Cell ◽  
Genetic Disorders ◽  
Cell Types ◽  
Protein Protein Interactions ◽  
Inborn Errors ◽  
Post Translational Modifications ◽  
New Genes ◽  
Inborn Errors Of Immunity

Inborn errors of immunity (IEI) are a group of genetic disorders that impair the immune system, with over 400 genes described so far, and hundreds more to be discovered. To facilitate the search for new genes, we need a way to prioritize among all the genes in the genome those most likely to play an important role in immunity. Here we identify a new list of genes by linking known IEI genes to new ones by using open-source databases of protein-protein interactions, post-translational modifications, and transcriptional regulation. We analyze this new set of 2,530 IEI-related genes for their tolerance of genetic variation and by their expression levels in various immune cell types.

scholarly journals AWARENESS OF DOCTORS AND PATIENTS ABOUT INBORN ERRORS OF IMMUNITY

2020 ◽  
Vol 11 (4) ◽  
pp. 16-21
Author(s):  
E.V. Zaitseva ◽  
Keyword(s):  
Quantitative Research ◽  
Complex Disease ◽  
Clinical Manifestations ◽  
The Body ◽  
Primary Immunodeficiencies ◽  
Malignant Neoplasms ◽  
Inborn Errors ◽  
Inborn Errors Of Immunity ◽  
Child Patient ◽  
Primary Care Doctors

The immune system protects the body. When defenses are compromised, people with hereditary immunological disorders become vulnerable to many life-threatening infections. Inborn errors of immunity (primary immunodeficiencies), manifested in patients in increased susceptibility to infectious diseases, autoimmune diseases, allergies, and malignant neoplasms. Today, this group of diseases is still considered quite rare. However, the development of diagnostic technologies expands the list of nosologies associated with inborn errors of immunity. Neonatal screening for inborn errors of immunity could solve many of the problems of these patients, but the procedure is not carried out in the Russian Federation. Therefore, diagnostics based on an analysis of the clinical manifestations of diseases. In most cases, the disease is diagnosed in early childhood. Here, the role of both the parents of the child-patient and the medical staff is important. The health and life of the child depends on their awareness of the disease, methods of diagnosis, treatment. This group of diseases is chronic, under an hour, severe. In the absence of timely diagnosis and proper therapy, it can be fatal. The article describes the experience of applied quantitative research conducted by the method of questioning patients with primary immunodeficiencies (parents of underage patients), about their disease, methods of treatment, problems arising in the long-term struggle with this complex disease. The author notes that patients and primary care doctors or general practitioners are poorly informed about diseases associated with primary immunodeficiencies. It is concluded that it is necessary to increase the informational medical culture of the population, especially the young, as participants in the interaction "doctor-patient" and representatives of the interests of minor children-patients with inborn errors of immunity.

The Prevalence of Atopic Manifestations in 313 Iranian Patients with Inborn Errors of Immunity

2021 ◽  
pp. 1-5
Author(s):  
Mehdi Ghaini ◽  
Mahnaz Jamee ◽  
Seyed Alireza Mahdaviani ◽  
Mehrnaz Mesdaghi ◽  
Shabnam Eskandarzadeh ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Food Allergy ◽  
Leukocyte Adhesion ◽  
Statistical Significance ◽  
Warning Signs ◽  
Inherited Disorders ◽  
Inborn Errors ◽  
Significance Level ◽  
Selective Iga Deficiency ◽  
Inborn Errors Of Immunity

<b><i>Introduction:</i></b> Inborn errors of immunity (IEIs) are rare inherited disorders with a broad spectrum of manifestations. Here, we aimed to delineate the atopy burden in a cohort of patients with IEIs. <b><i>Methods:</i></b> 313 patients with IEIs were enrolled in the study within a 9-years period, and data were collected via a questionnaire. All statistical analyses were performed using SPSS software (v. 25.0, Chicago, IL, USA). The statistical significance level was set at <i>p</i> &#x3c; 0.05. <b><i>Results:</i></b> Overall, 51 out of 313 (16.3%) patients were identified to have atopic manifestations. Food allergy was detected in 34 (10.2%), atopic dermatitis in 21 (6.7%), as well as allergic asthma and allergic rhinitis each in 4 (1.3%) patients. The allergic disorders were reported as initial manifestations among 14 out of 35 (40.0%) atopic patients. Most of these 51 patients fell within the category of combined immunodeficiency (CID) (<i>n</i> = 38, 74.5%), followed by, severe CID (SCID) (<i>n</i> = 5, 9.8%), common variable immunodeficiency (<i>n</i> = 3, 5.9%), chronic granulomatous disease (<i>n</i> = 3, 5.9%), selective IgA deficiency (<i>n</i> = 1, 2.0%), and leukocyte adhesion defect (<i>n</i> = 1, 2.0%). No patient with Mendelian susceptibility to mycobacteria was found to have atopic manifestation. Atopic dermatitis (<i>p</i> = 0.001) and food allergy (<i>p</i> &#x3c; 0.001) were both significantly higher in patients with CID than in other IEI groups. Among atopic patients with CID and SCID, food allergy and atopic dermatitis were the most prevalent comorbidities. <b><i>Discussion/Conclusion:</i></b> Atopic diseases may contribute to the clinical picture of IEIs, particularly in patients with CID. Atopy in association with other warning signs of IEIs increases the possibility of an underlying IEI.

Occurrence of Inborn Errors of Metabolism in newborns, diagnosis and prophylaxis

2020 ◽  
Vol 21 ◽  
Author(s):  
Alok Bharadwaj ◽  
Nitin Wahi ◽  
Aditya Saxena
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Metabolic Disorders ◽  
Genetic Disorders ◽  
Clinical Manifestations ◽  
High Sensitivity ◽  
Specific Gene ◽  
Inborn Errors ◽  
Genetic Manipulations ◽  
Enzyme Replacement ◽  
Intermediary Metabolite

: Inborn errors of metabolism (IEM) are heterogeneous group of rare genetic disorders which are generally transmitted as autosomal or X-linked recessive ones. These defects arise due to mutations associated with specific gene(s) especially the ones associated with key metabolic enzymes. These enzymes or their product(s) are involved in various metabolic pathways- leading to accumulation of intermediary metabolite(s), which reflects their toxic effects upon mutations. The diagnosis of these metabolic disorders is based on the biochemical analysis of the clinical manifestations produced and its molecular mechanism. It is therefore imperative to devise diagnostic tests with high sensitivity, and specificity for early detection of IEM. Recent advances in biochemical and polymerase chain reaction based genetic analysis along with pedigree and prenatal diagnosis can be life saving in nature. Latest development in exome sequencing for rapid diagnosis and enzyme replacement therapy would be expected to facilitate the successful treatment of these metabolic disorders in future. Although the long-term clinical implications of these genetic manipulations are still a matter of debate among the intellectuals and is a matter of further research.

scholarly journals Outcome of SARS-CoV-2 Infection in 121 Patients With Inborn Errors of Immunity: A Cross-sectional Study

2021 ◽  
Author(s):  
ekaterini goudouris ◽  
Fernanda Pinto-Mariz ◽  
Leonardo Oliveira Mendonça ◽  
Carolina Sanchez Aranda ◽  
Rafaela Rolla Guimarães ◽  
...  
Keyword(s):  
Clinical Manifestations ◽  
Case Fatality ◽  
Cross Sectional Study ◽  
Antibody Deficiency ◽  
Weak Correlation ◽  
Inborn Errors ◽  
Cross Sectional ◽  
Inborn Errors Of Immunity ◽  
Inflammatory Syndrome ◽  
Determining Factor

Abstract Purpose: There is still scarce data on SARS-CoV-2 infection in patients with Inborn Errors of Immunity (IEI) and many questions. We aimed to describe the clinical outcome of SARS-CoV-2 infection in Brazilian IEI patients and to identify factors influencing the outcome of infection.Methods: We did a cross-sectional, multicenter study that included patients of any age affected by IEI and SARS-CoV-2 infection. The variables studied were sex, age, type of IEI, comorbidities (number and type), treatment in use for IEI, clinical manifestations and severity of SARS-CoV-2 infection. Results: 121 patients were included: 55.4% female, ages from six months to 74 yo (median age = 25.1 yo). Most patients had predominantly antibody deficiency (n=53). The infection presented mostly as asymptomatic (n=21) and mild (n=66), and one child had multisystem inflammatory syndrome (MIS-C). We could not observe sex related susceptibility and observed a weak correlation between age and severity of infection. The number of comorbidities was higher in severe cases, particularly bronchiectasis and cardiopathy. There were no severe cases in hereditary angioedema patients. Six patients aged 2 to 74 years died, three of them with antibody deficiency. Conclusion: The outcome was mild in most patients, but the Case Fatality Ratio was higher than in the general population. Patients with complement deficiencies had milder COVID-19. However, the type of IEI was not a determining factor for severity. The severity of SARS-CoV-2 infection seems to be more related to older age, higher number of comorbidities and type of comorbidities (bronchiectasis and cardiopathy).

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