Inborn Errors of Adaptive Immunity in Down Syndrome

Verstegen, Ruud H J; Kusters, Maaike A.

doi:10.1007/s10875-020-00805-7

Cited by 36 publications

(29 citation statements)

References 145 publications

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“…Therefore, in contrast to others, immunodeficiency patients with DS show increased levels of IgG, with a demonstrated protective antibody response to pneumococcal and tetanus immunizations. However, it seems that compared to healthy subjects, the antibody levels of such patients in response to vaccination are more reduced and tend to decline more rapidly over time [13].…”

Section: Down Syndrome: Immune Dysregulationmentioning

confidence: 99%

“…When referring to HT, subclinical hypothyroidism is the most common biochemical pattern, frequently related to autoantibody formation (i.e., thyroid peroxidase (TPO) antibodies) and structural changes in the thyroid. In adults, up to 50% of individuals with Down syndrome have decreased thyroid function, and continued screening of thyroid stimulating hormone (TSH) and free T4 is advised at all ages [13]. On the contrary, with regard to GD, it appears as though there are no substantial differences among patients of the same age.…”

Section: Down Syndrome: Autoimmunity Predispositionmentioning

confidence: 99%

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Autoimmunity and Genetic Syndromes: A Focus on Down Syndrome

Ferrari

Stagi

2021

Genes

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Within immune system-related diseases, autoimmunity has always represented a field of great interest, although many aspects remain poorly understood even today. Genetic syndromes associated with immunity disorders are common and represent an interesting model for a better understanding of the underlying mechanism of autoimmunity predisposition. Among these conditions, Down syndrome (DS) certainly deserves special attention as it represents the most common genetic syndrome associated with immune dysregulation, involving both innate and adaptive immunity. Autoimmunity represents a well-known complication of DS: it is estimated that people affected by this disease present a risk four to six times higher than the normal population to develop autoimmune diseases such as celiac disease, type 1 diabetes mellitus, and hypo- or hyperthyroidism. Several factors have been considered as possible etiology, including genetic and epigenetic modifications and immune dysregulation. In times in which the life expectancy of people with DS has been extremely prolonged, thanks to improvements in the diagnosis and treatment of congenital heart disease and infectious complications, knowledge of the mechanisms and proper management of autoimmune diseases within this syndrome has become essential. In this short review, we aim to report the current literature regarding the genetic, immune, and environmental factors that have been proposed as the possible underlying mechanism of autoimmunity in individuals with DS, with the intent to provide insight for a comprehensive understanding of these diseases in genetic syndromes.

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Section: Down Syndrome: Immune Dysregulationmentioning

confidence: 99%

Section: Down Syndrome: Autoimmunity Predispositionmentioning

confidence: 99%

Autoimmunity and Genetic Syndromes: A Focus on Down Syndrome

Ferrari

Stagi

2021

Genes

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“…Solid malignancies (apart from testicular cancer) are less common, resulting in a lower overall risk for malignancies in Down syndrome [58,61,62]. Overexpression of DSCR1 and ZAKI-4 inhibits the transcription of calcineurindependent genes, by inhibiting the translocation of activated T lymphocyte nuclear factor (NF-AT) to the nucleus [63].…”

Section: Geneticsmentioning

confidence: 99%

“…Mainly the immune regulators encoded on chromosome 21 are four of the six interferon receptors: the two type I interferon (IFN) receptors IFNAR1 and IFNAR2, the type II IFN receptor IFNGR2, and IL10RB, which serve as receptor subunits not only for type III IFNs but also for cytokines IL-10, IL-22 and IL-2 [55][56][57]. These genes are overexpressed in all individuals with Down syndrome, regardless of sex, age, or ethnicity [58,59]. Furthermore, a positive feedback mechanism likely exists between pro-inflammatory cytokine production, the Aβ burden, and the APP level, present in DS and AD [48].…”

Section: Introductionmentioning

confidence: 99%

Down’s syndrome and COVID-19: risk or protection factor against infection? A molecular and genetic approach

Altable¹,

Serna

2020

Neurol Sci

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Down syndrome (DS) is the most common genetic cause of learning difficulties and intellectual disabilities. DS patients often present with several congenital defects and chronic diseases, including immunity disorders. Elevated levels of pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) have been seen, which appear to vary with age. At birth, patients present with combined immunodeficiency, with frequent infections that decrease with age. Furthermore, high levels of IL-4 and IL-10 with anti-inflammatory properties and low levels of IL-6 and TNF-α are described in children. The immune system is believed to play an essential role in SARS-CoV-2 pathogenesis, and it has been associated with elevated levels of pro-inflammatory cytokines and an exaggerated cytokine release syndrome (CRS) that may eventually trigger a severe situation called cytokine storm. On the other hand, genetic features seem to be involved in the predisposition to illness and its severity. Overexpression of DSCR1 and ZAKI-4 inhibits the translocation of activated T lymphocyte nuclear factor (NF-AT) to the nucleus, a main step in the inflammatory responsiveness. We discuss here the possible role of immunology and genetic features of DS in the infection and prognosis in COVID-19.

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“…Verstegen and Kusters review the literature on documented immune disbalance in DS, in particular in the adaptive immune system [5]. They point to inborn defects in thymic function, and the ensuing disbalance in T and B cell development.…”

mentioning

confidence: 99%

Bourgeoning Scientific Research in Down Syndrome

Bogunovic

2020

J Clin Immunol

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Inborn Errors of Adaptive Immunity in Down Syndrome

Cited by 36 publications

References 145 publications

Autoimmunity and Genetic Syndromes: A Focus on Down Syndrome

Autoimmunity and Genetic Syndromes: A Focus on Down Syndrome

Down’s syndrome and COVID-19: risk or protection factor against infection? A molecular and genetic approach

Bourgeoning Scientific Research in Down Syndrome

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