Primary Immune Deficiency Diseases Research Articles

General Population Awareness of Primary Immune Deficiency Disease in Children in the Arar Region, Saudi Arabia.

Background Primary immunodeficiency disorders (PIDD) are of various types and severities, and they are associated with a delay in diagnosis. Early diagnosis of PIDD helps to improve the quality of life of affected children and prevent permanent consequences such as organ damage. Hence, awareness of PIDD is a must in the community to aid in early detection. Objectives The study aims to investigate the general population's awareness of PIDD in children in Arar, Northern Saudi Arabia. Methods A cross-sectional design was utilized to determine the awareness of PIDD in children in Arar, Northern Saudi Arabia. The participants were selected through an online self-administered questionnaire. The collected data was analyzed using descriptive and inferential statistics. Results A total of528 participants were involved in the current study. The majority of the sample population falls within the 20-30 age range. 9.1% of respondents know a child with primary immunodeficiency. Additionally, participants were aware of certain symptoms, such as delayed growth and chronic diarrhea, with rates of 47.0% and 34.1%, respectively. On the other hand, symptoms like otitis media and sinusitis have lower awareness rates of 25.8% and 33.3%, respectively. Conclusion This study can help in developing targeted awareness campaigns and educational programs to improve the understanding of primary immune deficiency disease among the general population in Saudi Arabia. This, in turn, can lead to earlier diagnosis and better management of the disease in children, ultimately improving their quality of life.

Who's your data? Primary immune deficiency differential diagnosis prediction via machine learning and data mining of the USIDNET registry

PurposeThere are currently more than 480 primary immune deficiency (PID) diseases and about 7000 rare diseases that together afflict around 1 in every 17 humans. Computational aids based on data mining and machine learning might facilitate the diagnostic task by extracting rules from large datasets and making predictions when faced with new problem cases. In a proof-of-concept data mining study, we aimed to predict PID diagnoses using a supervised machine learning algorithm based on classification tree boosting. MethodsThrough a data query at the USIDNET registry we obtained a database of 2396 patients with common diagnoses of PID, including their clinical and laboratory features. We kept 286 features and all 12 diagnoses to include in the model. We used the XGBoost package with parallel tree boosting for the supervised classification model, and SHAP for variable importance interpretation, on Python v3.7. The patient database was split into training and testing subsets, and after boosting through gradient descent, the predictive model provides measures of diagnostic prediction accuracy and individual feature importance. After a baseline performance test, we used the Class Weighting Hyperparameter, or scale_pos_weight to correct for imbalanced classification. ResultsThe twelve PID diagnoses were CVID (1098 patients), DiGeorge syndrome, Chronic granulomatous disease, Congenital agammaglobulinemia, PID not otherwise classified, Specific antibody deficiency, Complement deficiency, Hyper-IgM, Leukocyte adhesion deficiency, ectodermal dysplasia with immune deficiency, Severe combined immune deficiency, and Wiskott-Aldrich syndrome. For CVID, the model found an accuracy on the train sample of 0.80, with an area under the ROC curve (AUC) of 0.80, and a Gini coefficient of 0.60. In the test subset, accuracy was 0.76, AUC 0.75, and Gini 0.51. The positive feature value to predict CVID was highest for upper respiratory infections, asthma, autoimmunity and hypogammaglobulinemia. Features with the highest negative predictive value were high IgE, growth delay, abscess, lymphopenia, and congenital heart disease. For the rest of the diagnoses, accuracy stayed between 0.75 and 0.99, AUC 0.46–0.87, Gini 0.07–0.75, and LogLoss 0.09–8.55. DiscussionClinicians should remember to consider the negative predictive features together with the positives. We are calling this a proof-of-concept study to continue with our explorations. A good performance is encouraging, and feature importance might aid feature selection for future endeavors. In the meantime, we can learn from the rules derived by the model and build a user-friendly decision tree to generate differential diagnoses.

Subcutaneous immunoglobulin 20% (Ig20Gly) treatment regimens in pediatric patients with primary immunodeficiencies – real-world data from the IG TATRY study

ABSTRACT Background Subcutaneous administration of immunoglobulins is associated with fewer systemic adverse events and easier infusion compared to intravenous administration. Ig20Gly is a 20% immunoglobulin formulation effective and safe in patients with primary immune deficiency diseases (PIDDs). Real-world data are scarce, therefore our study aimed to examine the real-life treatment regimen and clinical outcomes of Ig20Gly in Polish children with PIDDs. Researchdesign We retrospectively analyzed the medical documentation of 75 pediatric patients aged 0–17 years (mean 9.9) who received Ig20Gly (Cuvitru®; Baxalta US, Inc.; part of Takeda, MA, U.S.A.). Results The median exposure to treatment of the study population was 22.3 months. At the end of the study, 59 (78.7%) were still on Ig20Gly. The median monthly dose was 0.40 g/kg. The median treatment interval was 7.7 days. Most patients (96%) used one infusion site. The median infusion rate increased with patient age. The median IgG level in the study population, 8.0 g/L, was stable. There was one case of serious bacterial infection. Conclusion This is the largest, long-term real-world study to date on the treatment patterns of Ig20Gly in pediatric patients with PIDDs. The results of this study support the feasibility and tolerability of Ig20Gly usage in PIDD patients across the pediatric age spectrum. Trial registration The trial is registered at ClinicalTrials.gov (NCT04636502).

Prevention is Better than Cure! Can We prevent Primary Immune Deficiency Diseases?

Prevention is Better than Cure! Can We prevent Primary Immune Deficiency Diseases?

Clinical Case of X-Linked Lymphoproliferative Syndrome Burdened with Hemophagocytic Lymphohistiocytosis and Crohn's Disease

Background. X-linked lymphoproliferative (XLP) syndrome is hereditary disease with the incidence of 1-3 per 1 million born boys. This clinical case demonstrates a rare picture of XLP type 2 manifestation without prior Epstein-Barr virus.Clinical case description. Boy D., 15 years old, was admitted to Morozovskaya Children's City Hospital with complaints on fever, abdominal pain, loose stools, weight loss. The past medical history included hemophagocytic syndrome (remission) and acute erythema nodosum. We have performed several studies: abdominal ultrasound (hepatomegaly, dynamic changes in the intestine: parts of the small intestine were enlarged and walls were thickened, mass peristalsis, walls of transverse colon and descending colon are thickened up to 5 mm, mesenteric lymphadenopathy), rectosigmoidoscopy (high-activity ulcerative proctosigmoiditis corresponds to Crohn's disease), biochemical and clinical blood tests (active hemophagocytic syndrome), coagulogram (secondary hypocoagulation), myelogram (no data on hemoblastosis or aplastic condition). Virological blood tests (CMV, EBV, HHV-VI): negative. Laboratory and instrumental tests have revealed recurrence of hemophagocytic syndrome and Crohn's disease. The child was consulted by rheumatologist, hematologist, gastroenterologist, geneticist, neurologist, and clinical pharmacologist. The primary immune deficiency disease was suspected in this patient due to his medical history. Molecular genetic study was performed (deletion including the XIAP gene was revealed) and the diagnosis of primary immune deficiency was verified: X-linked lymphoproliferative syndrome type 2. Thus, allogeneic haematopoietic stem cell transplantation (HSCT) was performed.Conclusion. XLP diagnosis and management require multidisciplinary approach. The early diagnosis is crucial due to the high risk of secondary complications development that can significantly worsen the disease's prognosis. Allogeneic HSCT is the only effective treatment for the disease.

489 - Inflammatory Myositis As Late Complication of HSCT in Primary Immune Deficiency Disease

489 - Inflammatory Myositis As Late Complication of HSCT in Primary Immune Deficiency Disease

Granulomatous inflammation and hypogammaglobulinemia: Clinical conundrum of familial hemophagocytic lymphohistiocytosis type 5

Familial hemophagocytic lymphohistiocytosis (HLH) is an inherited disorder characterized by systemic hyperinflammation caused by an uncontrolled immune response mediated by T-lymphocytes, natural killer (NK) cells, and macrophages. Most children with familial HLH present within first 2 years of life and can have fatal disease unless hematopoietic stem cell transplant (HSCT) is performed (1). However, few patients may have late presentation and prolonged survival. With increasing awareness and facilities to identify HLH these disorders are being identified beyond infancy (2–4). Clinical and laboratory features are often similar to other primary immune deficiency diseases and pose diagnostic challenges (4–6). We report two patients who presented beyond the first decade of life with HLH, granulomatous inflammation, hypogammaglobulinemia, reduced B cells and were diagnosed to have familial HLH type 5 due to defect in STXBP2 gene.

Cardiac Complications in Patients with Common Variable Immune Deficiency: A Longitudinal Study

Background: The common variable immune deficiency (CVID) is known as the most prevalent symptomatic primary immune deficiency (PID) diseases, which is characterized by hypogammaglobulinemia with variable infectious and noninfectious manifestations. In this study, the researchers aimed to evaluate the frequency of cardiac disorders and investigate its association with other manifestations in CVID patients.
 Method: A total of 337 CVID patients registered in the Iranian Primary Immunodeficiency Registry were evaluated in this study. The questionnaire was completed for all patients to collect the participants’ demographic data, clinical manifestations and laboratory finding. The analysis was performed between the two groups of the study including CVID patients with cardiac manifestation and those without it.
 Results: The prevalence rate of cardiac manifestation was calculated to be 9.1%. pericardial and myocardial diseases and pulmonary hypertension were the most prevalent complications. CVID patients with a history of cardiac problem had significantly higher prevalence rates of otitis media, lymphoproliferative disorders, splenomegaly, hepatomegaly, failure to thrive and lower numbers of CD8+ T cells and CD19+ B cells compared to the patients without cardiac disorders. Notably, no significant differences were observed in immunoglobulins serum levels, CD3+ and CD4+ T cells between the patients with and without cardiac manifestation.
 Conclusion: Regular echocardiographic evaluation and of CVID patients for cardiac complications especially for inflammatory cardiac disease, heart failure and pulmonary hypertension, is critical to reduce the risk of heart disease.

Clinical Case of Job Syndrome in Infant

The article presents clinical case of Job syndrome, variant of primary immune deficiency disease confirmed genetically. This case is interesting for its early diagnosis due to comprehensive assessment of anamnestic, clinical, and laboratory data. Such typical phenotypic features as facial dysmorphisms, recurrent localized purulent infections, and laboratory parameters (absolute neutropenia and eosinophilia) were the major signs of autosomal dominant hyper IgE syndrome in a child with normal IgE levels. The combination of 2 heterozygous mutations in STAT3 gene inherited from his father and his mother has played its role in disease clinical features in the child.

Controversies about immunoglobulin replacement therapy in HSCT recipients with hypogammaglobulinemia.

The efficacy of immunoglobulin replacement therapy (IgRT) has been demonstrated for primary immune deficiency diseases and hematological malignancies such as chronic lymphocytic leukemia (CLL) or multiple myeloma with hypogammaglobulinemia. Clinical development of anti-B cell therapies including a monoclonal antibody, bispecific antibody, or chimeric antigen receptor T-cell therapy which could result in severe hypogammaglobulinemia accelerates the argument of prophylactic use of IgRT. Clinical guidelines for CLL describe immunoglobulin administration in patients with a low IgG who have experienced a severe/repeated bacterial infection. The utility in hematopoietic stem-cell transplantation (HSCT) remains unknown. Although an early randomized trial demonstrated that IgRT decreased infection risk and transplant-related mortality after HSCT, subsequent clinical trials could not validate the benefit. Consequently, a meta-analysis did not show the benefit of IgRT in HSCT. Most of the available data derives from matched-related HSCT using myeloablative regimen, and the impact in haploidentical and cord blood transplantation, or reduced-intensity HSCT remains unknown. One crucial issue is that no studies exist for patients with only hypogammaglobulinemia after HSCT. Other challenges are heterogeneous patient characteristics, or immunoglobulin formulation, dosage, schedule, route and duration of IgRT. Without evidence in HSCT, it would be reasonable to follow the guidelines for other diseases with hypogammaglobulinemia.

Кожные проявления первичных иммунодефицитных состояний

Primary immune deficiency diseases (PIDDs) are a group of severe genetically determined diseases caused by a disorder of the immunity links: humoral and cell-mediated links, phagocytosis, complement system. PIDDs are characterized by severe atypical recurrent infections, as well as autoimmune and oncological processes. In the case of clinical symptoms, skin manifestations in PIDDs allow to suspect the presence of congenital disorders of immunity. There is a technique in laboratory diagnostics of PIDDs, that determines a decrease in the number of T- and B-lymphocytes based on measuring the levels of TREC (T-cell Receptor Excision Circle) and KREC (Kappa-deleting Recombination Excision Circle), which are by-products of recombination of T- and B-cell receptor genes. TREC and KREC levels can be assessed using a reagent kit for quantifying TREC and KREC DNA by PCR in real time. The analysis can be conducted using both whole blood and DNA obtained from dried blood stains collected during the national newborn screening program. Today, quantitative analysis of TREC and KREC in dried blood stains on newborn screening cards is becoming the method of choice for newborn screening of PIDDs. The inclusion of the PIDDs diagnosis in the federal newborn screening program will allow detecting disorders of the immune system before their clinical manifestations, which will allow to apply modern treatment protocols, reduce disability and ensure high patient survival. KEYWORDS: TREC, KREC, PIDDs, newborn screening, PCR, immunity, early diagnosis. FOR CITATION: Churyukina E.V., Kudlay D.A. Skin manifestations of primary immune deficiency diseases. Russian Medical Inquiry. 2022;6(2):98–104 (in Russ.). DOI: 10.32364/2587-6821-2022-6-2-98-104

Primary Immune Deficiency Disease in Saudi Children: Systematic Review

The study aims to summarize current evidence regarding the primary immune deficiency disease in Saudi children. The PubMed database Information Services was utilized for article selection. In our review, we used all relevant articles related to our issue as well as unrelated publications. Other papers that were unrelated to this field were not considered. The data was extracted in a specified format, which the group members examined. Literature shows from the table it is clear that Combined immu

Legal and organizational healthcare environment for the children with primary immune deficiency disease in Russia

The aim of the research, the results of which are presented in the given article, comprises studying the state of legal and organizational healthcare environment provided to the Russian children with diseases caused by primary immune deficiency, as well as identifying the prospects for creating such environment. The relevance of the theme under study is due to the fact that the number of patients with diseases caused by primary immune deficiency is increasing in many countries, including the Russian Federation. This group includes more than 450 different diseases caused by defects in cells and proteins that are the components of the immune system. A significant number of Russian children suffer from diseases caused by severe combined immune deficiency: this is one of the most dangerous forms of primary immune deficiency disease. Hereditary conditions begin functioning even before the birth of a child, they are difficult to diagnose, often have fatal consequences, such as director disability and death. Their treatment requires special resources, such as high-tech medical care, emergency treatment, the use of special medical technologies, personnel and financial support. The authors of the article prove that difficulties and problems can be minimized in case of the implementation of the specific legislative and organizational actions.

Proteomics Profiling to Distinguish DOCK8 Deficiency From Atopic Dermatitis.

Dedicator of cytokinesis 8 deficiency is an autosomal recessive primary immune deficiency disease belonging to the group of hyperimmunoglobulinemia E syndrome (HIES). The clinical phenotype of dedicator of cytokinesis 8 (DOCK8) deficiency, characterized by allergic manifestations, increased infections, and increased IgE levels, overlaps with the clinical presentation of atopic dermatitis (AD). Despite the identification of metabolomics and cytokine biomarkers, distinguishing between the two conditions remains clinically challenging. The present study used a label-free untargeted proteomics approach using liquid-chromatography mass spectrometry with network pathway analysis to identify the differentially regulated serum proteins and the associated metabolic pathways altered between the groups. Serum samples from DOCK8 (n = 10), AD (n = 9) patients and healthy control (Ctrl) groups (n = 5) were analyzed. Based on the proteomics profile, the PLS-DA score plot between the three groups showed a clear group separation and sample clustering (R2 = 0.957, Q2 = 0.732). Significantly differentially abundant proteins (p < 0.05, FC cut off 2) were identified between DOCK8-deficient and AD groups relative to Ctrl (n = 105, and n = 109) and between DOCK8-deficient and AD groups (n = 85). Venn diagram analysis revealed a differential regulation of 24 distinct proteins from among the 85 between DOCK8-deficient and AD groups, including claspin, haptoglobin-related protein, immunoglobulins, complement proteins, fibulin, and others. Receiver-operating characteristic curve (ROC) analysis identified claspin and haptoglobin-related protein, as potential biomarkers with the highest sensitivity and specificity (AUC = 1), capable of distinguishing between patients with DOCK8 deficiency and AD. Network pathway analysis between DOCK8-deficiency and AD groups revealed that the identified proteins centered around the dysregulation of ERK1/2 signaling pathway. Herein, proteomic profiling of DOCK8-deficiency and AD groups was carried out to determine alterations in the proteomic profiles and identify a panel of the potential proteomics biomarker with possible diagnostic applications. Distinguishing between DOCK8-deficiency and AD will help in the early initiation of treatment and preventing complications.

Clinical and immunological assessment of children with ataxia telangiectasia attending Sohag university hospital in Upper Egypt

Ataxia Telangiectasia (AT) is a very rare autosomal recessive primary immune deficiency (PID) disease that affects 1 in 10,000-40,000 new births per year in the world. It is caused by biallelic mutations in ataxia telangiectasia mutated (ATM) gene and characterized by a progressive cerebellar ataxia. The clinical profile of AT children in Upper Egypt in missing. Herein, we evaluated the clinical characteristics and immunological profiles of patients with AT attending Sohag University Hospital. This was a cross-sectional study, included 21 AT patients attending the Neurological and Immunological Units, Pediatric Department, Sohag University Hospital, starting April 2018 to the end of March 2019. AT represented 20.5% of all PID patients attending the hospital. The most common type of humoral immune deficiency in patients with AT was specific IgA deficiency (52.3%) followed by hypogammaglobulinemia (23.8%). Recurrent sinopulmonary infection with different degrees of severity was the common immunological problem. The most common neurological manifestations in our studied patients, other than the ataxia, were language delay and eye movement abnormalities followed by developmental delay and head nodding. None of our patients had developed malignancy till the end of the study.

Rapid Rate Intravenous Immunoglobulin Administration: Safety Outcomes in 11,334 Infusions

A national home infusion services provider (KabaFusion, LLC) traditionally administered intravenous immunoglobulin (IVIG) at conservative maximum infusion rates to minimize adverse drug reactions (ADRs). The objective of this retrospective observational study was to identify the impact of increased on-label infusion rates of a specific, high-purity product (Octagam) on patient safety. The study included all patients who received IVIG over a 10-year period. The study population was composed of both adult and pediatric patients, with neuroimmune, neuromuscular disorders, and primary immune deficiency diseases warranting IVIG treatment. Patients were divided into two randomized groups to provide an even distribution for analysis: those who received IVIG infusions at a rate of &lt;110 mL/hr (Group 1) and those who received IVIG at ³110 mL/hr (Group 2). There were 489 patients identified for inclusion in Group 1 (n=245) and Group 2 (n=244). Demographics (gender, age) and exposure (number of infusions) were similar between both groups.&#x0D; &#x0D; The study data included 11,334 total IVIG infusions with a total of 392 ADRs (3.5%). ADRs in the high infusion rate group (Group 2) were significantly lower (5.1% vs.1.8%, p&lt;0.0001). In addition, the incidence of non-serious ADRs in Group 2 (1.7%) vs. Group 1 (4.8%) were also significantly lower in the high infusion rate group (p&lt;0.0001). The number of serious adverse drug reactions (SADRs) was lower in Group 2 but did not reach statistical significance (Group 1: 0.3% vs Group 2:0.1%, p=0.0741). Based on these results, infusion rates of specific high-purity IVIG products were associated with statistically and clinically significant lower non serious ADRs in both the adult and pediatric populations, in addition to having an association of clinical significance in both for SADRs. These results can be of great utility in clinical application if applied within the manufacturer’s recommended guidelines, to ease the burden of time required for patients undergoing IVIG infusions.

Health disparities in allergic and immunologic conditions in racial and ethnic underserved populations: A Work Group Report of the AAAAI Committee on the Underserved

Health disparities are health differences linked with economic, social, and environmental disadvantage. They adversely affect groups that have systematically experienced greater social or economic obstacles to health. Renewed efforts are needed to reduced health disparities in the United States, highlighted by the disparate impact on racial minorities during the coronavirus pandemic. Institutional or systemic patterns of racism are promoted and legitimated through accepted societal standards, and organizational processes within the field of medicine, and contribute to health disparities. Herein, we review current evidence regarding health disparities in allergic rhinitis, asthma, atopic dermatitis, food allergy, drug allergy, and primary immune deficiency disease in racial and ethnic underserved populations. Best practices to address these disparities involve addressing social determinants of health and adopting policies to improve access to specialty care and treatment for the underserved through telemedicine and community partnerships, cross-cultural provider training to reduce implicit bias, inclusion of underserved patients in research, implementation of culturally competent patient education, and recruitment and training of health care providers from underserved communities. Addressing health disparities requires a multilevel approach involving patients, health providers, local agencies, professional societies, and national governmental agencies.

A New Intravenous Immune Globulin: Novel or Not?

To assess the clinical use and determine the place in therapy for immune globulin intravenous (IV), human-slra, a recently approved IV immune globulin for the treatment of primary immune deficiency diseases (PIDD). A PubMed and MEDLINE search (2010 to April 2020) was conducted for relevant articles. Data were also obtained from the package insert. English language publications regarding the clinical efficacy and safety of immune globulin-slra were analyzed. Publications focused on use of immune globulin products were also included. Immune globulin-slra is indicated for patients with PIDD and was specifically developed to include donor plasma with high respiratory syncytial virus (RSV) antibody titers. Efficacy was demonstrated through favorable incidence of infections and infection-related complications. Patients treated with immune globulin-slra had increases in anti-RSV neutralizing antibody titers compared with baseline. Adverse events occurred at rates similar to or less than other available immune globulin products. This review describes a new immune globulin product available for use in patients with PIDD. A novel approach to managing patients at risk of serious infections may be to utilize products with formulations proven to not only boost IgG levels, but also antibodies to specific pathogens. The choice of which immune globulin product to select for a patient or formulary is complex. Each product is unique, and differences between products should be taken into consideration, along with cost and availability.

Evaluation of the frequency and diagnostic delay of primary immunodeficiency disorders among suspected patients based on the 10 warning sign criteria: A cross-sectional study in Iran

IntroductionThe prevalence of undiagnosed primary immunodeficiency diseases is remarkably high and contributes to increasing the rate of morbidity and mortality among this group of patients. ObjectiveTo examine the 10 warning sign scoring system in patients suspected of primary immune deficiency and also estimate the diagnostic delay in patients with proven disease. MethodsThis descriptive cross-sectional study was carried out during the years 2015–2016 in Ali Asghar (AS) Clinic and Hospital. Two hundred patients with suspected primary immune deficiency disease were eligible for inclusion in the study. Multivariable logistic regression analysis was used to determine the relation between findings. ResultsIn this study, the majority of suspected cases of immunodeficiency were males (57%) with a mean age of 3.33±2.89 years. Twenty-one (10.5%) patients were diagnosed with immunodeficiency disease. The mean diagnostic delay among primary immune deficient patients was 2.05±1.7 years. There was a significant relationship between having parental consanguinity (OR=2.68, 95% CI: 1.07–6.70), allergies (OR=5.03, 95% CI: 1.13–22.31), vaccine adverse effects (OR=9.31, 95% CI: 1.24–69.96) and primary immune deficiency diagnosis. No association was observed between age (OR=0.98, 95% CI: 0.84–1.14), gender (OR=0.99, 95% CI: 0.39–2.47), immune deficiency scoring (OR=0.68, 95% CI: 0.31–1.45) and primary immune deficiency diagnosis. ConclusionTen warning sign scoring system is of less value to consider a patient suspected of having primary immune deficiency. There is a meaningful delay in diagnosis of primary immune deficiencies especially in antibody deficiency defects which seeks further upgrading of knowledge in physicians.

Type 2 immunity in the skin and lungs.

There has been extensive progress in understanding the cellular and molecular mechanisms of inflammation and immune regulation in allergic diseases of the skin and lungs during the last few years. Asthma and atopic dermatitis (AD) are typical diseases of type 2 immune responses. interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin are essential cytokines of epithelial cells that are activated by allergens, pollutants, viruses, bacteria, and toxins that derive type 2 responses. Th2 cells and innate lymphoid cells (ILC) produce and secrete type 2 cytokines such as IL-4, IL-5, IL-9, and IL-13. IL-4 and IL-13 activate B cells to class-switch to IgE and also play a role in T-cell and eosinophil migration to allergic inflammatory tissues. IL-13 contributes to maturation, activation, nitric oxide production and differentiation of epithelia, production of mucus as well as smooth muscle contraction, and extracellular matrix generation. IL-4 and IL-13 open tight junction barrier and cause barrier leakiness in the skin and lungs. IL-5 acts on activation, recruitment, and survival of eosinophils. IL-9 contributes to general allergic phenotype by enhancing all of the aspects, such as IgE and eosinophilia. Type 2 ILC contribute to inflammation in AD and asthma by enhancing the activity of Th2 cells, eosinophils, and their cytokines. Currently, five biologics are licensed to suppress type 2 inflammation via IgE, IL-5 and its receptor, and IL-4 receptor alpha. Some patients with severe atopic disease have little evidence of type 2 hyperactivity and do not respond to biologics which target this pathway. Studies in responder and nonresponder patients demonstrate the complexity of these diseases. In addition, primary immune deficiency diseases related to T-cell maturation, regulatory T-cell development, and T-cell signaling, such as Omenn syndrome, severe combined immune deficiencies, immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome, and DOCK8, STAT3, and CARD11 deficiencies, help in our understanding of the importance and redundancy of various type 2 immune components. The present review aims to highlight recent advances in type 2 immunity and discuss the cellular sources, targets, and roles of type 2 mechanisms in asthma and AD.