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Abstract Background Autosomal recessive hyper-IgE syndrome (AR-HIES) caused by DOCK8 gene is a rare immunodeficiency disease, the main clinical manifestations include recurrent Eczema-like rash, skin and lung abscesses, accompanied with increased serum IgE level. Here, we report a 7-year-old Chinese girl with a new clinic features caused by DOCK8 gene mutations. Case presentation A 7-year-old girl was admitted to our hospital because of abnormal walking posture. The clinical manifestations of the patient included abnormal gait, eczema-like rash, fingertip abscess, high muscle tone, and facial paralysis. Among them, high muscle tone and facial paralysis are new clinic features which have not been reported previously. The blood eosinophils and serum IgE levels were significantly increased, and the lymphocyte subsets indicated a decrease of T lymphocytes. The magnetic resonance imaging (MRI) of her brain suggested myelin dysplasia and brain atrophy. Two novel compound heterozygous mutations (c.1868 + 2 T > C and c.5962-2A > G) of DOCK8 gene were identified by whole exome sequencing. By literature review, there are 11 mutations of DOCK8 gene in Chinese AR-HIES patients. Conclusions Two novel splice-site mutations(c.1868 + 2 T > C and c.5962-2A > G) of DOCK8 gene and new clinic features were found in a Chinese girl with AR-HIES, which extends our understanding of DOCK8 gene mutation spectrum and phenotype of AR-HIES in children.

Background: Hyper‐IgE syndromes (HIES) are distinct diseases characterized by recurrent cutaneous and lung infections, eczema, and elevated serum IgE level. Methods: In this study, clinical manifestations, immunologic findings, and genetic studies of all patients with HIES in the Iranian national registry database were evaluated. Results: A total of 129 HIES patients with a median age of 14.0 (9.0‐24.0) years were followed up for a total of 307.8 patient‐years. Genetic studies showed heterozygous STAT3 mutations in 19 patients and homozygous DOCK8 mutation in 16 patients. The mean of National Institutes of Health score in STAT3‐deficient patients was higher than in patients with DOCK8 mutation (P = 0.001). It was shown that the presence of pneumatocele and hematologic complication were significantly frequent in STAT3‐deficient cases compared to patients with DOCK8 deficiency (P = 0.001 and P = 0.002, respectively). Moreover, the median IgE serum levels were higher in patients with STAT3 gene mutation than in patients with DOCK8 gene mutation (P = 0.02). The eosinophils' count was enhanced in patients with DOCK8 deficiency than in patients with STAT3 gene defects (P = 0.02). Conclusion: Specific molecular study of STAT3 and DOCK8 mutations in patients with HIES clinical phenotype could help the physician to definitively characterize the disease. Since HIES showed the highest rate of unsolved combined immunodeficiency, investigation of other genetic and environmental factors could also help in understanding the mechanism of remaining patients as well as providing strategy into therapeutic modalities. [ABSTRACT FROM AUTHOR]

Autosomal recessive hyper-IgE syndrome caused by DOCK8 gene mutation is an immunodeficiency. However, the presentation of a tumour-like lesion of the lip in autosomal recessive hyper-IgE syndrome has not yet been reported. This article reports the case of a 20-year-old man with autosomal recessive hyper-IgE syndrome who presented with a tumour-like lesion of the lip, and hyperplasia and erosion of the gingiva. The clinical manifestations included coarse face and neck skin, a diffuse tumour-like lesion on the upper lip showing a reddish erosive nodular surface with yellowish-white exudation, erosive buccal mucosa, and severe periodontitis. The swollen gingival and palatal mucosa indicated nodular hyperplasia and redness with pseudomembrane. The patient had a significantly increased peripheral blood eosinophil count and serum IgE level and an abnormal T lymphocyte count. His oral lesions improved markedly after prednisolone acetate use and local symptomatic treatment for 2 years. However, the patient unfortunately died of a cerebral infection 6 months after the oral lesions had resolved. The novel features of the labial tumour-like lesion described here extend our understanding of the manifestations of autosomal recessive hyper-IgE syndrome. [ABSTRACT FROM AUTHOR]

Hydroa vacciniforme lymphoproliferative disorders (HVLPD) fall within the clinical spectrum of chronic active epstein barr virus (EBV) disease (CAEBVD), ranging from localised and/or indolent forms (classic HVLPD) to systemic disease with fever, hepatosplenomegaly and lymphadenopathy (systemic HVLPD). A preadolescent male with 47XYY, multicystic dysplastic kidney, autism spectrum disorder and Attention-deficit/hyperactivity disorder (ADHD) presented with photodistributed nonpruritic, non-painful necrotic papulovesicles accompanied by non-febrile intermittent fatigue and lymphadenopathy. The patient had a history of EBV pneumonia in infancy confirmed by CT scan and was later diagnosed with CAEBV. Despite presenting without the typical risk factors of East Asian or Latin American background, young adulthood onset and long-standing classic HVLPD, the patient’s CAEBVD, systemic symptoms and gamma–delta T-cell clonal expansion were consistent with a diagnosis of systemic HVLPD. Systemic HVLPD is high-risk for malignant transformation, requiring close follow-up to evaluate for HV-like T-cell lymphoma. Due to the patient’s risk factors and findings consistent with systemic HVLPD, the patient is regularly surveilled for progression to lymphoma. [ABSTRACT FROM AUTHOR]

Dedicator of cytokinesis 8 (DOCK8) deficiency represents a primary immunodeficiency with a wide range of clinical symptoms, including recurrent infections, atopy, and increased malignancy risk. This study presents a case of a 6-year-old girl with DOCK8 deficiency, characterized by severe, treatmentresistant herpetic infections who was successfully treated with siltuximab and glucocorticoids. The successful use of siltuximab in achieving remission highlights the pivotal role of interleukin-6 (IL-6) in DOCK8 deficiency pathogenesis and suggests that IL-6 modulation can be critical in managing DOCK8 deficiency-related viral infections, which may inform future therapeutic strategies for DOCK8 deficiency and similar immunodeficiencies. [ABSTRACT FROM AUTHOR]

This study investigated the association between autoimmunity and immunodeficiency in pediatric patients, focusing on the case of a 15-year-old female diagnosed with juvenile idiopathic arthritis (JIA) and secondary Sjögren's syndrome. The patient presented with a variety of symptoms, including joint pain, bronchial asthma, leukopenia, and skin lesions. Genetic testing revealed a de novo mutation in the DOCK8 gene, associated with DOCK8 deficiency, a condition usually associated with immunodeficiencies. The clinical course, diagnostic pathway, and treatment history are detailed, highlighting the importance of molecular diagnostics in understanding the genetic basis of rheumatic diseases. This case highlights the need to consider innate immune errors in patients with multiple diseases or atypical symptoms of rheumatic diseases. Furthermore, the study highlights the importance of targeted treatment, including genetic counseling, to improve patient outcomes. The observed association between autoimmunity and immune deficiency reinforces the importance of molecular testing in elucidating the causes of previously idiopathic rheumatic diseases, contributing to improved patient care and quality of life. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to describe the clinical, immunological, and genetic features of patients with DOCK8 deficiency (DOCK8‐Def) in a tertiary care center for children. Methods: Retrospective chart review of patients' clinical, immunological, and genetic characteristics with DOCK8‐Def. Genetic analysis was performed with targeted‐ or whole‐exome sequencing; we also assessed DOCK8 protein expression and a lymphoproliferation assay and analyzed survival by the Kaplan–Meier method. Results: We described 11 patients from 8 unrelated kindreds. The median age at symptoms' onset was 10 months (range 1–54 months). The median follow‐up time was 53.4 months (4.8–118.8). All patients presented eczema and recurrent sinopulmonary and cutaneous infections. Besides those symptoms, the most frequent manifestations were bronchiectases (8/11), food allergies (6/11), and severe infections (6/11). Infrequent characteristics were detection of CMV in bronchial lavage, C. parvum‐driven sclerosing cholangitis, Takayasu vasculitis, neurological syndromes, pulmonary tuberculosis, and lymphomatoid granulomatosis. Conclusion: DOCK8‐Def has a broad spectrum of manifestations, including allergy, autoimmunity, inflammation, infection, and cancer. The hallmark of this inborn error of immunity is IEI‐associated eczema with eosinophilia and increased IgE. Here, we report six new mutations causing human DOCK8 deficiency and symptoms previously unrecognized to occur in DOCK8‐Def. Therefore, an early diagnosis of DOCK8‐Def is essential to facilitate an adequate treatment such as HSCT. [ABSTRACT FROM AUTHOR]

Job's syndrome or hyper-immunoglobulin E syndrome (HIES) is a heterogeneous complex of immunodeficiencies distinguishes by skin abscesses, recurrent pneumatoceles or staphylococcal infections, high serum immunoglobulin E levels and eczematous dermatitis. It has two types depends on type of gene involved; autosomal-dominant HIES (AD-HIES), which develops due to signal transducer and activator of transcription 3 gene and autosomal recessive HIES caused by DOCK8 gene mutation. Hereby we present a case of 13-month-old male child who admitted to our hospital with pustular lesions on the neck, face and upper chest associated with itching; some of these were hemorrhaged and crusted. The complete clinical presentation and lab investigations have confirmed AD-HIES syndrome. The therapeutic strategy was directed mainly toward the prevention and management of infections and symptoms. This case presents the clinical features, investigational procedures and management strategy for that particular condition in pediatrics. [ABSTRACT FROM AUTHOR]

DOCK8 deficiency is the most common cause of autosomal recessive hyper-IgE syndrome (AR-HIES). The clinical spectrum is wide resulting in combined immunodeficiency, atopy, autoimmunity, and malignancies. To study the clinical and molecular profile of 20 patients with DOCK8 deficiency. Four hundred and eight patients with various inborn errors of immunity (IEIs) were diagnosed in the Pediatric Immunology Unit of our hospital during the study period of February 2017 to August 2023. Based on the clinical and immunological phenotype, DOCK8 deficiency was suspected in 31 patients. Genetic studies confirmed DOCK8 deficiency in 20 patients, and their profile was analyzed in detail. Twenty patients from 17 kindreds were diagnosed with DOCK8 deficiency. The female-to-male ratio was 1.2:1. The mean age at onset of symptoms and diagnosis was 9.8 and 69.8 months, respectively. Thirteen out of 17 families (76%) reported consanguinity. Eczema was the presenting manifestation in 19 patients (95%). Mucocutaneous manifestations included oromucosal hyperpigmentation (n = 8), scalp seborrhoea (n = 2), psoriasis (n = 2), and alopecia (n = 1). The spectrum of infections included pneumonia (n = 14), otitis media (n = 6), gastrointestinal infections (n = 6), cutaneous viral infections (n = 5), oral candidiasis (n = 4), and meningoencephalitis (n = 2). Three patients had developed bronchiectasis. Four patients had autoimmune manifestations including autoimmune hemolytic anemia (n = 2) and vasculitis (n = 2). The whole exome sequencing showed deletions (8 kindreds) as the most common mutation in the DOCK8 gene. Overall, 11 of these mutations were novel. Ten patients were on monthly intravenous immunoglobulin therapy and antibiotic prophylaxis at the time of writing this paper. Three patients underwent hematopoietic stem cell transplants elsewhere, two of whom succumbed to post-transplant complications and one is doing well. Nine patients died during the study period. We present one of the largest single-center experiences on DOCK8 deficiency from India. A significant delay in the diagnosis contributed to poor outcomes in our cohort., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Hyperimmunoglobulin E syndrome (HIES) is a group of rare genetic disorders characterized by severe atopic dermatitis and recurrent skin and pulmonary infections. The efficacy of dupilumab in pediatric patients with HIES-associated severe atopic dermatitis is relatively understudied. Here, we present a series of three children with HIES, two with AD-HIES caused by STAT3 mutations, and one with AR-HIES caused by biallelic mutations in ZNF341. In all cases, dupilumab treatment led to sustained clearance of severe atopic dermatitis over multiple years, as well as improvements in systemic symptoms of HIES., (© 2024 The Author(s). Pediatric Dermatology published by Wiley Periodicals LLC.)

The hyper-immunoglobulin E syndrome (HIES) is a primary immunodeficiency disease originally described as Job syndrome. The fundamental causative variant of the HIES is an autosomal dominant mutation in the signal transducer and activator of transcription 3 (STAT3) gene. It is characterized by recurrent staphylococcal cold skin abscess, sinopulmonary infection, eczema, head and face anomalies, frequent bone fractures, eosinophilia and extremely high serum IgE levels (IgE ≥ 2000 IU/mL). However, multiple other genetic defects are also known as HIES-like disorders. Apart from infectious manifestations, STAT3, DOCK8 and TYK2 gene mutations are associated with various malignancies. The most common malignancies reported in these patients are lymphomas, including Hodgkin's and non-Hodgkin's lymphomas (NHL) of B and T cells. This systematic review aimed to investigate the prevalence of malignancies in HIES and the factors associated with malignancy in these patients. In this survey, all articles published until April 1st, 2023, in Scopus, PubMed and Web of Science databases based on three groups of keywords related to HIES syndrome and malignancy were reviewed by three different researchers. Finally, 26 articles were evaluated from which 24 papers were meta-analyzed. In the current study, the demographic information of 1133 patients with HIES, which was mentioned in 24 articles enrolled in the project, was collected, and the information related to patients who had malignancy was analyzed and meta-analyzed. A total of 96 patients out of 1133 studied patients had at least one type of malignancy, the overall prevalence of malignancies reported in the articles was 6.5% (95% confidence interval 4.1–9%), and the total prevalence of malignancy in patients with NHL type and patients with squamous cell carcinoma (SCC) was 2.9% (95% confidence interval 1.7–4.4%) and 2.2% (95% confidence interval 0.3–4.1%), respectively. The results of this study indicated that in 6.5% of cases, HIES was complicated with malignancy, and considering the higher rate of these malignancies in women as well as in DOCK8 mutation sufferers, it is necessary for physicians to be aware of this association and includes malignancy screening in follow-up and periodic examinations of these patients. Indeed, more studies in this field will help to clarify the precise figures and predisposing factors of the relationship between HIES and malignancy. [ABSTRACT FROM AUTHOR]

Hyper-immunoglobulin E syndrome is a rare primary immunodeficiency syndrome characterized by severe atopic dermatitis, recurrent pulmonary and staphylococcal skin infections. Its diagnosis requires a high degree of suspicion, typical clinical features, and not mere rise in serum IgE levels. Genetic studies are not always possible in a resource poor setting in developing countries. In this case series, all children had recurrent eczematoid rash, secondary infections, multiple episodes of hospitalization for pulmonary infection and raised serum IgE levels. Diagnostic genetic study was feasible in only one of the cases which revealed pathogenic homozygous deletions of exons 15 to 18 (Transcript: NM_203447) in DOCK8 gene. The main goal of management of hyper-immunoglobulin E syndrome is aggressive treatment of infections and optimum skin care. Our case series highlights various characteristic, presentations, and management of this rare syndrome childhood cases. Awareness of these manifestations may facilitate early identification and contribute to optimal care of patients as representative data on the same is limited in literature. [ABSTRACT FROM AUTHOR]

Background: Mepolizumab 300 mg is an approved treatment option for patients with eosinophilic granulomatosis with polyangiitis (EGPA), yet, the adequacy of 100 mg of mepolizumab in disease control is controversial. Objective: To evaluate the sinonasal and respiratory outcomes of EGPA patients treated with 100 mg mepolizumab for one year. Methods: Evaluations of 11 patients were made of the sinonasal outcome test (SNOT-22) (nasal, otologic, sleep, and emotional domains), asthma control test (ACT), forced expiratory volume in 1 s (FEV1), blood eosinophil counts and oral steroid doses before mepolizumab treatment (T0) and at the 6th (T6) and 12th (T12) months. Results: A significant decrease was observed in the total SNOT-22 scores in the 6th month, after which the scores continued to be stable until the 12th month. (SNOT-22 median (IQR); T0: 70(53-82); T6: 19(4-35); T12: 11(6-40); T0-T6, p = 0.02; T6-T12, p = 0.85). In the subdomains of SNOT-22, nasal and sleep-related domains improved significantly in the first 6 months, and the otologic and emotional domains only improved from baseline in the 12th month. There was a significant decrease in blood eosinophil counts in the 6th month and oral steroid dose in the 12th month (eosinophils, median(IQR), T0: 1000(700-1800), T6: 100(0-200), p = 0.02; OCS dose, median(IQR), T0: 16(8-16); T6: 4(0-4); T12: 0(0-4); T0-T12, p = 0.002). A significant improvement was observed in ACT values in the 6th month (ACT median (IQR); T0:16(8-18); T6: 22(21-25); p = 0.01). Conclusion: Mepolizumab 100 mg provided a significant decrease in SNOT-22 values, especially in nasal and sleep domains, eosinophil counts and OCS dose in the 6th month. [ABSTRACT FROM AUTHOR]

X-linked hyper-immunoglobulin M (X-HIGM) syndrome and autosomal recessive hyper-immunoglobulin E syndrome (HIES) are rare inborn errors of immunity characterized by recurrent infections due to immune system impairment. In this study, we identified a novel hemizygous CD40 ligand (CD40L) mutation and compound heterozygous dedicator of cytokinesis-8 (DOCK8) mutations in two Han Chinese families with X-HIGM and HIES, respectively. We aimed to investigate the association between their genotypes and phenotypes. Genomic DNA was extracted from peripheral blood samples obtained from the families. Whole exome sequencing and Sanger sequencing were performed to identify and verify pathogenic variants in the two families. Clinical analyses of the probands were also performed. A novel hemizygous mutation of CD40L in exon 2 (c.257delA) was identified in the first proband, resulting in the substitution of glycine with glutamic acid at codon 86 of the protein. This leads to premature termination of translation at downstream codon 9 (p.E86Gfs*9). Sanger sequencing confirmed that the variant was inherited from the mother. The second proband carried two novel compound heterozygous mutations in DOCK8: one at exon 14 (c.1546C > G) inherited from the father, and the other at intron 41 (c.5355 + 6C > T; splicing) inherited from the mother. This study enhances our understanding of the pathogenetic mutation spectrum of CD40L and DOCK8 genes, facilitating the prenatal diagnosis of X-HIGM and HIES and enabling timely treatment of patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Mediastinal masses are commonly identified in the pediatric population with cross-sectional imaging central to the diagnosis and management of these lesions. With greater anatomical definition afforded by cross-sectional imaging, classification of mediastinal masses into the traditional anterior, middle and posterior mediastinal compartments — as based on the lateral chest radiograph — has diminishing application. In recent years, the International Thymic Malignancy Interest Group (ITMIG) classification system of mediastinal masses, which is cross-sectionally based, has garnered acceptance by multiple thoracic societies and been applied in adults. Therefore, there is a need for pediatric radiologists to clearly understand the ITMIG classification system and how it applies to the pediatric population. The main purpose of this article is to provide an updated review of common pediatric mediastinal masses and mediastinal manifestations of systemic disease processes in the pediatric population based on the new ITMIG classification system. [ABSTRACT FROM AUTHOR]

Copyright of Revista Alergia de Mexico is the property of Coleg. Mexicano de Inmunologia Clinica y Alergia A.C.; Soc. Lat. de Alergia, Asma e Inmunologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The laboratory rat has been used for a long time as the model of choice in several biomedical disciplines. Numerous inbred strains have been isolated, displaying a wide range of phenotypes and providing many models of human traits and diseases. Rat genome mapping and genomics was considerably developed in the last decades. The availability of these resources has stimulated numerous studies aimed at discovering causal disease genes by positional identification. Numerous rat genes have now been identified that underlie monogenic or complex diseases and remarkably, these results have been translated to the human in a significant proportion of cases, leading to the identification of novel human disease susceptibility genes, helping in studying the mechanisms underlying the pathological abnormalities and also suggesting new therapeutic approaches. In addition, reverse genetic tools have been developed. Several genome-editing methods were introduced to generate targeted mutations in genes the function of which could be clarified in this manner [generally these are knockout mutations]. Furthermore, even when the human gene causing a disease had been identified without resorting to a rat model, mutated rat strains (in particular KO strains) were created to analyze the gene function and the disease pathogenesis. Today, over 350 rat genes have been identified as underlying diseases or playing a key role in critical biological processes that are altered in diseases, thereby providing a rich resource of disease models. This article is an update of the progress made in this research and provides the reader with an inventory of these disease genes, a significant number of which have similar effects in rat and humans. [ABSTRACT FROM AUTHOR]

Background: The cytokine IL-17 is a key player in autoimmune processes, while the cytokine IL-6 is responsible for the chronification of inflammation. However, their roles in type 1 diabetes development are still unknown.Methods: Therefore, therapies for 5 days with anti-IL-17A or anti-IL-6 in combination with a T cell-specific antibody, anti-TCR, or in a triple combination were initiated immediately after disease manifestation to reverse the diabetic metabolic state in the LEW.1AR1-iddm (IDDM) rat, a model of human type 1 diabetes.Results: Monotherapies with anti-IL-6 or anti-IL-17 showed no sustained anti-diabetic effects. Only the combination therapy of anti-TCR with anti-IL-6 or anti-IL-17 at starting blood glucose concentrations up to 12 mmol/l restored normoglycaemia. The triple antibody combination therapy was effective even up to very high initial blood glucose concentrations (17 mmol/l). The β cell mass was raised to values of around 6 mg corresponding to those of normoglycaemic controls. In parallel, the apoptosis rate of β cells was reduced and the proliferation rate increased as well as the islet immune cell infiltrate was strongly reduced in double and abolished in triple combination therapies.Conclusions: The anti-TCR combination therapy with anti-IL-17 preferentially raised the β cell mass as a result of β cell proliferation while anti-IL-6 strongly reduced β cell apoptosis and the islet immune cell infiltrate with a modest increase of the β cell mass only. The triple combination therapy achieved both goals in a complimentary anti-autoimmune and anti-inflammatory action resulting in sustained normoglycaemia with normalized serum C-peptide concentrations. [ABSTRACT FROM AUTHOR]

The article discusses the case study of the 6-year-old boy, resident of Haryana (India), presented with complaints of high-grade fever and swelling in left thigh for 14 days and the child developed vessel wall injury and was referred to a higher center for cardiothoracic vascular opinion, during the course of treatment, fever subsided, the lesions started healing and no new lesions were seen and antibiotic therapy was completed and the child was discharged on cotrimoxazole and iron supplements.

The LEW.1AR1-iddm rat is an animal model of human type 1 diabetes, which arose through a spontaneous mutation in the Dock8 gene within the MHC congenic background strain LEW.1AR1. This mutation not only mediates diabetes development but also leads to a variable T cell frequency in peripheral blood. In this study, the immune cell frequencies of primary and secondary lymphatic organs of LEW.1AR1-iddm rats were analysed at days 40 and 60 and compared to other MHC congenic LEW rat strains. In LEW.1AR1-iddm rats, the secondary lymphatic organs such as lymph nodes and spleen showed a reduced, around 15% in comparison to all other strains, but very variable T cell frequency, mirroring the fluctuating T cell content in blood. On the other hand, the frequency of B cells was increased by 10% in the lymph nodes and by 5% in the spleen. Thus, the decreasing number of T cells in blood could not be caused by an increase of T cells in secondary lymphatic organs. The frequency of single- or double-positive T cells in the thymus was unaffected. The T cell frequencies in the other analysed strains were more stable and mostly higher in all secondary lymphatic organs. Obviously, the Dock8 mutation leads to variabilities of T cell frequencies in blood as well as in secondary lymphatic organs. In conclusion, the Dock8 mutation was responsible for changed immune cell frequencies in different compartments and together with the RT1B/Du haplotype causing immune imbalances and development of autoimmune diabetes. [ABSTRACT FROM AUTHOR]

Drosophila melanogaster has been used as a very versatile and potent model in the past few years for studies in metabolism and metabolic disorders, including diabetes types 1 and 2. Drosophila insulin signaling, despite having seven insulin-like peptides with partially redundant functions, is very similar to the human insulin pathway and has served to study many different aspects of diabetes and the diabetic state. Yet, very few studies have addressed the chronic nature of diabetes, key for understanding the full-blown disease, which most studies normally explore. One of the advantages of having Drosophila mutant viable combinations at different levels of the insulin pathway, with significantly reduced insulin pathway signaling, is that the abnormal metabolic state can be studied from the onset of the life cycle and followed throughout. In this review, we look at the chronic nature of impaired insulin signaling. We also compare these results to the results gleaned from vertebrate model studies. [ABSTRACT FROM AUTHOR]

Allergies are rapidly worsening in recent decades, representing the most common immunological diseases. The mechanism of disorders such as asthma, rhinocongiuntivitis, urticaria, atopic dermatitis, food and drug allergies, and anaphylaxis still remain unclear and consequently treatments is mostly still symptomatic and aspecific while developments of new therapies are limited. A growing amount of data in the literature shows us how the prevalence of allergic diseases is different in both sexes and its changes over the course of life. Genes, hormones, environmental and immunological factors affect sex disparities associated with the development and control of allergic diseases, while they more rarely are considered and reported regarding their differences related to social, psychological, cultural, economic, and employment aspects. This review describes the available knowledge on the role of sex and gender in allergies in an attempt to improve the indispensable gender perspective whose potential is still underestimated while it represents a significant turning point in research and the clinic. It will offer insights to stimulate exploration of the many aspects still unknown in this relationship that could ameliorate the preventive, diagnostic, and therapeutic strategies in allergic diseases. [ABSTRACT FROM AUTHOR]

In this study, we report a complete (clinical, radiological, and virological) sustained (1 year) response after nivolumab salvage therapy in a progressive multifocal leukoencephalopathy patient. Analyses of the cells infiltrate in a pretreatment brain biopsy suggest that parenchymal programmed cell death-L1+ macrophages could be the T-cells partnership in immune exhaustion and virus escape. [ABSTRACT FROM AUTHOR]