[52]200925 DS subjectsDS subjects: mean age =?12

[52]200925 DS subjectsDS subjects: mean age =?12.2?yearsReduction of percentages and total numbers of CD4+ T cells. known genetic disorder 8-Gingerol associated with moderate to severe intellectual disability, happening in approximately 1 out of every 600C700 live births [1, 2]. DS Rabbit Polyclonal to C56D2 is related to a chromosomal disorder, related to a total or partial trisomy of the autosomal chromosome 21. Even if during the past decades life expectancy in DS populace has greatly improved [3C6], DS individuals have still higher mortality rates as compared with additional populations [7, 8]. In addition to indicators specifically associated with their congenital syndrome, subjects with DS appear to age in a different way from the general populace, and it is obvious that they present symptoms of ageing ahead of time, leading to the classical description of DS like a progeroid syndrome and as a model of accelerated ageing [9C12]. In this work, we review how the trend of ageing effects the immune system in DS subjects. We firstly describe medical features of DS individuals from an immune perspective. We then summarize evidence on immunosenescence in DS subjects and how it effects both innate and adaptive immunity, as well as chronic swelling. Finally, we discuss the potentially age-associated mechanisms involved. Accelerated and atypical ageing in Down syndrome DS has long been considered as a progeroid syndrome, as individuals with trisomy 21 start to age prematurely and present precociously conditions usually characteristic of the geriatric populace [9C12]. The aging process in DS subjects not only seems to be premature/accelerated but also appears to be atypical and segmental, as it recapitulates many, but not all, of the classical signs and symptoms of ageing [13, 14]. Clinically, DS subjects present indicators of early ageing influencing particularly the neurological system, with an extremely high prevalence of dementia of Alzheimers type [15]. Ageing affects also prematurely the dermatological, sensory, endocrine, and musculoskeletal systems, leading to high levels of mortality and multi-morbidity with this populace [16]. From a biological perspective, the same pattern of accelerated ageing has been observed with the use of ageing biomarkers [17]. The latest and powerful decades of biomarkers which are based on different approaches have been applied to cohorts of DS adults. Interestingly, these different biomarkers display concordantly accelerated ageing in subjects with DS, whether epigenetic clocks [18, 19], metabolic biomarkers such as GlycoAge [20], or expected brain age [21] are tested. Clinical features suggesting an immune impairment in Down syndrome individuals Significant evidence has accumulated within the existence of an immune dysregulation in DS, existing from the very beginning of the existence 8-Gingerol of DS individuals. Firstly, it has been observed that DS subjects are characterized by a higher susceptibility to bacterial infections as compared with the general populace, with especially a higher incidence of recurrent and chronic respiratory tract ones [22C25]. DS individuals have furthermore modified reactions to vaccinations with conjugate or toxoid vaccines [26C29]. These suboptimal antibody reactions potentially get 8-Gingerol worse the trend of higher susceptibility to infections. Finally, DS subjects possess regularly high levels of autoantibodies. While some of them seem to be not related to an eventual clinical significance [30], the others are 8-Gingerol associated with a higher incidence of organ-specific autoimmune disorders, affecting 8-Gingerol especially the endocrine system [31C33]. This clinical picture recapitulates the increased incidence of infections, the failure of vaccination, and the high prevalence of autoantibodies that can be observed in older people of the general population, supporting here also the concept of DS as an accelerated aging syndrome. This clinical presentation is the reflect of important alterations in immune homeostasis in DS with significant perturbations in all branches of the immune system, some of them being common with the.