Autoimmunity and Genetic Syndromes: A Focus on Down Syndrome

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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Permutational immune analysis reveals architectural similarities between inflammaging, Down syndrome and autoimmunity

10.1101/2021.09.13.460115 ◽

2021 ◽

Author(s):

Katharina Lambert ◽

Keagan G. Moo ◽

Azlann Arnett ◽

Gautam Goel ◽

Kaitlin J. Flynn ◽

...

Keyword(s):

Type 1 Diabetes ◽

Down Syndrome ◽

Autoimmune Diseases ◽

Immune Dysregulation ◽

Cellular Composition ◽

Cell Compartment ◽

Novel Approach ◽

Quantitative Understanding ◽

Age And Sex

AbstractPeople with Down syndrome show cellular and clinical features of dysregulated aging of the immune system, including naïve-memory shift in the T cell compartment and increased incidence of autoimmunity. However, a quantitative understanding of how various immune compartments change with age in Down syndrome remains lacking. Here we performed deep immunophenotyping of a cohort of individuals with Down syndrome across the lifespan, selecting for individuals not affected by autoimmunity. We simultaneously interrogated age- and sex-matched healthy neurotypical controls and people with type 1 diabetes, as a representative autoimmune disease. We built a new analytical software, IMPACD, that enabled us to rapidly identify many features of immune dysregulation in Down syndrome that are recapitulated in other autoimmune diseases. We found significant quantitative and qualitative dysregulation of naïve CD4+ and CD8+ T cells in Down syndrome and identified IL-6 as a candidate driver of some of these changes, thus extending the consideration of immunopathologic cytokines in Down syndrome beyond interferons. Notably, we successfully used immune cellular composition to generate three quantitative models of aging (i.e. immune clocks) trained on control subjects. All three immune clocks demonstrated significantly advanced immune aging in people with Down syndrome. Notably, one of these clocks, informed by Down syndrome-relevant biology, also showed advanced immune aging in people with type 1 diabetes. Together, our findings demonstrate a novel approach to studying immune aging in Down syndrome which may have implications in the context of other autoimmune diseases.One Sentence SummaryPermutational analysis of immune landscape reveals advanced immune aging in people with Down syndrome and in people with type 1 diabetes.

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Microduplication of 15q13.3 and Microdeletion of 18q21.32 in a Patient with Moyamoya Syndrome

International Journal of Molecular Sciences ◽

10.3390/ijms19113675 ◽

2018 ◽

Vol 19 (11) ◽

pp. 3675 ◽

Cited By ~ 2

Author(s):

Francesca Luisa Sciacca ◽

Ambra Rizzo ◽

Gloria Bedini ◽

Fioravante Capone ◽

Vincenzo Di Lazzaro ◽

...

Keyword(s):

Internal Carotid ◽

Neurofibromatosis Type ◽

Genetic Syndromes ◽

Genetic Syndrome ◽

Susceptibility Factors ◽

The Relationship ◽

Genic Mutation ◽

Internal Carotid Arteries ◽

Cerebral Angiopathy

Moyamoya angiopathy (MA) is a cerebrovascular disease determining a progressive stenosis of the terminal part of the internal carotid arteries (ICAs) and their proximal branches and the compensatory development of abnormal “moyamoya” vessels. MA occurs as an isolated cerebral angiopathy (so-called moyamoya disease) or in association with various conditions (moyamoya syndromes) including several heritable conditions such as Down syndrome, neurofibromatosis type 1 and other genomic defects. Although the mechanism that links MA to these genetic syndromes is still unclear, it is believed that the involved genes may contribute to the disease susceptibility. Herein, we describe the case of a 43 years old woman with bilateral MA and peculiar facial characteristics, having a 484-kb microduplication of the chromosomal region 15q13.3 and a previously unreported 786 kb microdeletion in 18q21.32. This patient may have a newly-recognized genetic syndrome associated with MA. Although the relationship between these genetic variants and MA is unclear, our report would contribute to widening the genetic scenario of MA, in which not only genic mutation, but also genome unbalances are possible candidate susceptibility factors.

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Features of the ovarian reserve of women of reproductive age suffering from autoimmune diseases

GYNECOLOGY ◽

10.26442/20795696.2020.5.200416 ◽

2020 ◽

Vol 22 (5) ◽

pp. 27-30

Author(s):

Elena N. Andreeva ◽

Olga R. Grigoryan ◽

Yulia S. Absatarova ◽

Irina S. Yarovaya ◽

Robert K. Mikheev

Keyword(s):

Type 1 Diabetes ◽

Thyroid Gland ◽

Autoimmune Diseases ◽

Ovarian Reserve ◽

Reproductive Potential ◽

Reproductive Age ◽

Control Group ◽

Antithyroid Antibodies ◽

Healthy Women

The reproductive potential of a woman depends on indicators of the ovarian reserve, such as the anti-Muller hormone (AMH) and the number of antral follicles (NAF). Autoimmune diseases have a significant effect on fertility and contribute to the development of premature ovarian failure. Aim.To evaluate the parameters of the ovarian reserve in patients with type 1 diabetes mellitus, carriers of antibodies to the thyroid gland in a state of euthyroidism and compare them with similar parameters in healthy women. Materials and methods.In the first block of the study, the level of AMH, follicle-stimulating hormone, luteinizing hormone, NAF was studied among 224 women with diabetes and 230 healthy women in the control group. In block II, the level of the above hormonal indices was studied in 35 carriers of antithyroid antibodies in the state of euthyroidism and 35 healthy women. Results.In patients with type 1 diabetes, the level of AMH, NAF was statistically significantly lower when compared with the control group. Among carriers of antithyroid antibodies and healthy women, no difference in AMH and NAF was found. Conclusion.The autoimmune processes accompanying diabetes are more influenced by the ovarian reserve indices than autoimmune aggression to the tissues of the thyroid gland.

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PREDICTION OF OCCURRENCE AND THE RELATIONSHIP OF AUTOIMMUNE DISEASES IN CHILDREN WITH TYPE 1 DIABETES

European Science Review ◽

10.29013/esr-19-5.6-41-43 ◽

2019 ◽

pp. 41-43

Author(s):

A. A. Sadirkhodjaeva ◽

D. T. Ashurova

Keyword(s):

Type 1 Diabetes ◽

Autoimmune Diseases ◽

Relationship Of ◽

The Relationship

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SARS-CoV-2 Entry: At the Crossroads of CD147 and ACE2

Cells ◽

10.3390/cells10061434 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1434

Author(s):

Claudio Fenizia ◽

Silvia Galbiati ◽

Claudia Vanetti ◽

Riccardo Vago ◽

Mario Clerici ◽

...

Keyword(s):

Underlying Mechanism ◽

Membrane Receptors ◽

Host Cells ◽

Viral Agent ◽

Blocking Antibody ◽

Angiotensin Converting Enzyme 2 ◽

Host Membrane ◽

B Virus ◽

Immunodeficiency Virus

In late 2019, the betacoronavirus SARS-CoV-2 was identified as the viral agent responsible for the coronavirus disease 2019 (COVID-19) pandemic. Coronaviruses Spike proteins are responsible for their ability to interact with host membrane receptors and different proteins have been identified as SARS-CoV-2 interactors, among which Angiotensin-converting enzyme 2 (ACE2), and Basigin2/EMMPRIN/CD147 (CD147). CD147 plays an important role in human immunodeficiency virus type 1, hepatitis C virus, hepatitis B virus, Kaposi’s sarcoma-associated herpesvirus, and severe acute respiratory syndrome coronavirus infections. In particular, SARS-CoV recognizes the CD147 receptor expressed on the surface of host cells by its nucleocapsid protein binding to cyclophilin A (CyPA), a ligand for CD147. However, the involvement of CD147 in SARS-CoV-2 infection is still debated. Interference with both the function (blocking antibody) and the expression (knock down) of CD147 showed that this receptor partakes in SARS-CoV-2 infection and provided additional clues on the underlying mechanism: CD147 binding to CyPA does not play a role; CD147 regulates ACE2 levels and both receptors are affected by virus infection. Altogether, these findings suggest that CD147 is involved in SARS-CoV-2 tropism and represents a possible therapeutic target to challenge COVID-19.

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PREDICTION AND ANALYSIS OF VACCINATION POSSIBILITIES IN AUTOIMMUNE DISEASES: AN APPLICATION OF ARTIFICIAL IMMUNE SYSTEM

Journal of Biological System ◽

10.1142/s0218339002000536 ◽

2002 ◽

Vol 10 (02) ◽

pp. 107-126

Author(s):

RAJANI R. JOSHI ◽

BHUVANESWARAN NATARAJAN

Keyword(s):

Autoimmune Diseases ◽

Lupus Erythematosus ◽

Artificial Immune System ◽

Real Data ◽

Affinity Maturation ◽

Artificial Immune ◽

Humoral Immune ◽

Machine Learning Model ◽

Experimental Findings

We present an adaptive machine learning model of the humoral immune response. Antigens (epitopes/ids) and antibodies (paratopes/anti-ids) are represented here as sequences of single letter amino acid codes. The model effectively simulates dynamic affinity maturation, memory and associativity. Specific age-function is derived here based on recent experimental findings and is used to incorporate self and non-self antigens. Computational experiments using real data on Type-1 Diabetes and Systemic Lupus Erythematosus offer quantitative elucidation of autoimmunity. The results also provide applications towards vaccine design and possible solution to the therapeutic difficulties in the autoimmune diseases and disorders of the above kind.

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The Na/K-ATPase Signaling: From Specific Ligands to General Reactive Oxygen Species

International Journal of Molecular Sciences ◽

10.3390/ijms19092600 ◽

2018 ◽

Vol 19 (9) ◽

pp. 2600 ◽

Cited By ~ 11

Author(s):

Rebecca Pratt ◽

Cameron Brickman ◽

Cameron Cottrill ◽

Joseph Shapiro ◽

Jiang Liu

Keyword(s):

Reactive Oxygen Species ◽

Positive Feedback ◽

Reactive Oxygen ◽

Underlying Mechanism ◽

Short Review ◽

Oxygen Species ◽

Signaling Function ◽

Amplification Loop

The signaling function of the Na/K-ATPase has been established for 20 years and is widely accepted in the field, with many excellent reports and reviews not cited here. Even though there is debate about the underlying mechanism, the signaling function is unquestioned. This short review looks back at the evolution of Na/K-ATPase signaling, from stimulation by cardiotonic steroids (also known as digitalis-like substances) as specific ligands to stimulation by reactive oxygen species (ROS) in general. The interplay of cardiotonic steroids and ROS in Na/K-ATPase signaling forms a positive-feedback oxidant amplification loop that has been implicated in some pathophysiological conditions.

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Sudden Cause of Cardiac Death—Be Aware of Me: A Case Report and Short Review on Brugada Syndrome

Case Reports in Medicine ◽

10.1155/2010/823490 ◽

2010 ◽

Vol 2010 ◽

pp. 1-3 ◽

Cited By ~ 3

Author(s):

Jagadeesh K. Kalavakunta ◽

Vishwaroop Bantu ◽

Hemasri Tokala ◽

Mihas Kodenchery

Keyword(s):

Brugada Syndrome ◽

Past History ◽

Short Review ◽

Case Presentation ◽

St Segment Elevation ◽

First Case ◽

St Segment ◽

The Right ◽

Malignant Arrhythmias

Introduction. Brugada syndrome accounts for about 4% of sudden cardiac deaths (SCD). It is characterized by an ST-segment elevation in the right precordial electrocardiogram (EKG) leads.Case Presentation. We describe a 39-year-old healthy Caucasian man who was admitted to the intensive care unit after being cardioverted from ventricular fibrillation (VF) arrest. His past history was significant for an episode of syncope one month prior to this presentation for which he was admitted to an outlying hospital. EKG during that admission showed ST elevations in V1 and V2 leads, a pattern similar to Type 1 Brugada. A diagnosis of Brugada syndrome was missed and the patient had a cardiac arrest a month later. We discuss a short review of Brugada syndrome and emphasize the need to look for it in patients presenting with SCD and malignant arrhythmias.Conclusion. Physicians should always consider Brugada syndrome in the differential diagnosis of ST-segment elevation in anterior precordial leads of EKG and associated VT/VF. Although more than 17 years have passed since the first case was reported, increased awareness of this syndrome is needed to identify patients with EKG changes and treat them accordingly to prevent incidence of (SCD) and its deleterious complications.

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