scholarly journals Endocrinopathies in Inborn Errors of Immunity

2021 ◽  
Vol 12 ◽  
Author(s):  
Kei Takasawa ◽  
Hirokazu Kanegane ◽  
Kenichi Kashimada ◽  
Tomohiro Morio
Keyword(s):  
Adrenal Insufficiency ◽  
Growth Failure ◽  
Endocrine System ◽  
Autoimmune Response ◽  
Clinical Feature ◽  
Endocrine Disorders ◽  
Energy Regulation ◽  
Inborn Errors ◽  
Hematopoietic Stem ◽  
Inborn Errors Of Immunity

Inborn errors of immunity (IEI), caused by hereditary or genetic defects, are a group of more than 400 disorders, in which the immune system, including lymphocytes, neutrophils, macrophages, and complements, does not function properly. The endocrine system is frequently affected by IEI as an associated clinical feature and a complex network of glands which regulate many important body functions, including growth, reproduction, homeostasis, and energy regulation. Most endocrine disorders associated with IEI are hypofunction which would be treated with supplementation therapy, and early diagnosis and appropriate management are essential for favorable long-term outcomes in patients with IEI. In this review, we aimed to comprehensively summarize and discuss the current understanding on the clinical features and the pathophysiology of endocrine disorders in IEI. This review is composed with three parts. First, we discuss the two major pathophysiology of endocrinopathy in IEI, autoimmune response and direct effects of the responsible genes. Next, the details of each endocrinopathy, such as growth failure, hypothyroidism, hypoparathyroidism, adrenal insufficiency, diabetes mellitus (DM) are specified. We also illustrated potential endocrinopathy due to hematopoietic stem cell transplantation, including hypogonadism and adrenal insufficiency due to glucocorticoid therapy.

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 Treatment of immune-mediated cytopenias in patients with primary immunodeficiencies and immune regulatory disorders (PIRDs)

Hematology ◽  
2020 ◽  
Vol 2020 (1) ◽  
pp. 673-679
Author(s):  
Markus G. Seidel
Keyword(s):  
Lupus Erythematosus ◽  
Bone Marrow Failure ◽  
Primary Immunodeficiencies ◽  
Definitive Treatment ◽  
Inborn Errors ◽  
Hematopoietic Stem ◽  
Rheumatologic Diseases ◽  
Inborn Errors Of Immunity ◽  
Immune Mediated ◽  
Regulatory Disorders

Abstract Severe immune cytopenias (SICs) are rare acquired conditions characterized by immune-mediated blood cell destruction. They may necessitate emergency medical management and long-term immunosuppressive therapy, strongly compromising the quality of life. The initial diagnostic workup involves excluding malignancies, congenital cytopenias, bone marrow failure syndromes, infections, and rheumatologic diseases such as systemic lupus erythematosus. Causal factors for SIC such as primary immunodeficiencies or immune regulatory disorders, which are referred to as inborn errors of immunity (IEIs), should be diagnosed as early as possible to allow the initiation of a targeted therapy and avoid multiple lines of ineffective treatment. Ideally, this therapy is directed against an overexpressed or overactive gene product or substitutes a defective protein, restoring the impaired pathway; it can also act indirectly, enhancing a countermechanism against the disease-causing defect. Ultimately, the diagnosis of an underling IEI in patients with refractory SIC may lead to evaluation for hematopoietic stem cell transplantation or gene therapy as a definitive treatment. Interdisciplinary care is highly recommended in this complex patient cohort. This case-based educational review supports decision making for patients with immune-mediated cytopenias and suspected inborn errors of immunity.

How I Treat: Allogeneic HSCT for adults with Inborn Errors of Immunity

Blood ◽  
2021 ◽  
Author(s):  
Siobhan Burns ◽  
Emma C Morris
Keyword(s):  
Patient Selection ◽  
Severe Disease ◽  
Severe Infection ◽  
Cell Transplant ◽  
Inherited Disorders ◽  
Inborn Errors ◽  
Hematopoietic Stem ◽  
Inborn Errors Of Immunity ◽  
Long Term Follow Up ◽  
History Of

Inborn Errors of Immunity (IEI) are rare inherited disorders arising from monogenic germline mutations in genes that regulate the immune system. The majority of IEI are Primary Immunodeficiencies characterised by severe infection often associated with autoimmunity, autoinflammation and/or malignancy. Allogeneic hematopoietic stem cell transplant (HSCT) has been the corrective treatment of choice for many IEI presenting with severe disease in early childhood and experience has made this a successful and comparatively safe treatment in affected children. Early HSCT outcomes in adults were poor, resulting in extremely limited use worldwide. This is changing due to a combination of improved IEI diagnosis to inform patient selection, better understanding of the natural history of specific IEI and improvements in transplant practice. Recently published HSCT outcomes for adults with IEI have been comparable with pediatric data, making HSCT an important option for correction of clinically severe IEI in adulthood. Here we discuss our practice for patient selection, timing of HSCT, donor selection and conditioning, peri- and post HSCT management and our approach to long term follow up. We stress the importance of multidisciplinary involvement in the complex decision-making process that we believe is required for successful outcomes in this rapidly emerging area.

scholarly journals Stem Cell-Based Disease Models for Inborn Errors of Immunity

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 108
Author(s):  
Aline Zbinden ◽  
Kirsten Canté-Barrett ◽  
Karin Pike-Overzet ◽  
Frank J. T. Staal
Keyword(s):  
Stem Cell ◽  
Disease Modeling ◽  
Induced Pluripotent Stem Cell ◽  
Disease Models ◽  
Inborn Errors ◽  
Hematopoietic Stem ◽  
Inborn Errors Of Immunity ◽  
Induced Pluripotent

The intrinsic capacity of human hematopoietic stem cells (hHSCs) to reconstitute myeloid and lymphoid lineages combined with their self-renewal capacity hold enormous promises for gene therapy as a viable treatment option for a number of immune-mediated diseases, most prominently for inborn errors of immunity (IEI). The current development of such therapies relies on disease models, both in vitro and in vivo, which allow the study of human pathophysiology in great detail. Here, we discuss the current challenges with regards to developmental origin, heterogeneity and the subsequent implications for disease modeling. We review models based on induced pluripotent stem cell technology and those relaying on use of adult hHSCs. We critically review the advantages and limitations of current models for IEI both in vitro and in vivo. We conclude that existing and future stem cell-based models are necessary tools for developing next generation therapies for IEI.

scholarly journals Sepsis as a Pan-Endocrine Illness—Endocrine Disorders in Septic Patients

2021 ◽  
Vol 10 (10) ◽  
pp. 2075
Author(s):  
Weronika Wasyluk ◽  
Martyna Wasyluk ◽  
Agnieszka Zwolak
Keyword(s):  
Host Response ◽  
Peripheral Resistance ◽  
Endocrine System ◽  
Endocrine Disorders ◽  
Hormonal Changes ◽  
Adrenergic Stimulation ◽  
Hypothalamic Amenorrhea ◽  
Somatotropic Axis ◽  
Almost All ◽  
Triiodothyronine Concentration

Sepsis is defined as “life-threatening organ dysfunction caused by a dysregulated host response to infection”. One of the elements of dysregulated host response is an endocrine system disorder. Changes in its functioning in the course of sepsis affect almost all hormonal axes. In sepsis, a function disturbance of the hypothalamic–pituitary–adrenal axis has been described, in the range of which the most important seems to be hypercortisolemia in the acute phase. Imbalance in the hypothalamic–pituitary–thyroid axis is also described. The most typical manifestation is a triiodothyronine concentration decrease and reverse triiodothyronine concentration increase. In the somatotropic axis, a change in the secretion pattern of growth hormone and peripheral resistance to this hormone has been described. In the hypothalamic–pituitary–gonadal axis, the reduction in testosterone concentration in men and the stress-induced “hypothalamic amenorrhea” in women have been described. Catecholamine and β-adrenergic stimulation disorders have also been reported. Disorders in the endocrine system are part of the “dysregulated host response to infection”. They may also affect other components of this dysregulated response, such as metabolism. Hormonal changes occurring in the course of sepsis require further research, not only in order to explore their potential significance in therapy, but also due to their promising prognostic value.

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