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Clinical Reviews in Allergy & Immunology Aug 2023Primary immunodeficiency (PID) may impact any component of the immune system. The number of PID and immune dysregulation disorders is growing steadily with advancing... (Review)
Review
Primary immunodeficiency (PID) may impact any component of the immune system. The number of PID and immune dysregulation disorders is growing steadily with advancing genetic detection methods. These expansive recognition methods have changed the way we characterize PID. While PID were once characterized by their susceptibility to infection, the increase in genetic analysis has elucidated the intertwined relationship between PID and non-infectious manifestations including autoimmunity. The defects permitting opportunistic infections to take hold may also lead the way to the development of autoimmune disease. In some cases, it is the non-infectious complications that may be the presenting sign of PID autoimmune diseases, such as autoimmune cytopenia, enteropathy, endocrinopathies, and arthritis among others, have been reported in PID. While autoimmunity may occur with any PID, this review will look at certain immunodeficiencies most often associated with autoimmunity, as well as their diagnosis and management strategies.
Topics: Humans; Autoimmunity; Immunologic Deficiency Syndromes; Thrombocytopenia
PubMed: 35648371
DOI: 10.1007/s12016-022-08942-0 -
The Journal of the Association of... Jan 2020
Topics: Autoimmune Diseases; Autoimmunity; Humans
PubMed: 31979706
DOI: No ID Found -
Nature Aging Oct 2022Immune system and blood-brain barrier dysfunction are implicated in the development of Alzheimer's and other dementia-causing diseases, but their causal role remains...
Immune system and blood-brain barrier dysfunction are implicated in the development of Alzheimer's and other dementia-causing diseases, but their causal role remains unknown. We performed Mendelian randomization for 1,827 immune system- and blood-brain barrier-related biomarkers and identified 127 potential causal risk factors for dementia-causing diseases. Pathway analyses linked these biomarkers to amyloid-β, tau and α-synuclein pathways and to autoimmunity-related processes. A phenome-wide analysis using Mendelian randomization-based polygenic risk score in the FinnGen study (n = 339,233) for the biomarkers indicated shared genetic background for dementias and autoimmune diseases. This association was further supported by human leukocyte antigen analyses. In inverse-probability-weighted analyses that simulate randomized controlled drug trials in observational data, anti-inflammatory methotrexate treatment reduced the incidence of Alzheimer's disease in high-risk individuals (hazard ratio compared with no treatment, 0.64, 95% confidence interval 0.49-0.88, P = 0.005). These converging results from different lines of human research suggest that autoimmunity is a modifiable component in dementia-causing diseases.
Topics: Humans; Autoimmunity; Mendelian Randomization Analysis; Alzheimer Disease; Biomarkers; Autoimmune Diseases; Immune System
PubMed: 37118290
DOI: 10.1038/s43587-022-00293-x -
Current Rheumatology Reviews 2024Cells transmit information to the external environment and within themselves through signaling molecules that modulate cellular activities. Aberrant cell signaling... (Review)
Review
Cells transmit information to the external environment and within themselves through signaling molecules that modulate cellular activities. Aberrant cell signaling disturbs cellular homeostasis causing a number of different diseases, including autoimmunity. Scaffold proteins, as the name suggests, serve as the anchor for binding and stabilizing signaling proteins at a particular locale, allowing both intra and intercellular signal amplification and effective signal transmission. Scaffold proteins play a critical role in the functioning of tight junctions present at the intersection of two cells. In addition, they also participate in cleavage formation during cytokinesis, and in the organization of neural synapses, and modulate receptor management outcomes. In autoimmune settings such as lupus, scaffold proteins can lower the cell activation threshold resulting in uncontrolled signaling and hyperactivity. Scaffold proteins, through their binding domains, mediate protein- protein interaction and play numerous roles in cellular communication and homeostasis. This review presents an overview of scaffold proteins, their influence on the different signaling pathways, and their role in the pathogenesis of autoimmune and auto inflammatory diseases. Since these proteins participate in many roles and interact with several other signaling pathways, it is necessary to gain a thorough understanding of these proteins and their nuances to facilitate effective target identification and therapeutic design for the treatment of autoimmune disorders.
Topics: Humans; Autoimmune Diseases; Autoimmunity; Signal Transduction
PubMed: 37670692
DOI: 10.2174/1573397119666230904151024 -
Seminars in Cancer Biology Aug 2020In the last decades, many studies conducted in vitro, and in vivo, have shown that thyroid autoimmunity and thyroid cancer (TC) (mainly papillary TC) can be concomitant,... (Review)
Review
In the last decades, many studies conducted in vitro, and in vivo, have shown that thyroid autoimmunity and thyroid cancer (TC) (mainly papillary TC) can be concomitant, even if the exact mechanisms at the basis of this association are still not clear. Growing incidence of TC coincides with increased registration of autoimmune thyroid disorders (AITD) suggesting an association between those pathologies. Elevated TSH levels and thyroid autoimmunity were defined as independent risk factors for TC. However a lot of evidence suggests that autoimmunity and inflammation, per se, are risk factors for TC. The link between inflammation and TC involves multiple components of the immune system, extracellular matrix, stroma, and adipose tissue, with pro-tumoral activity of inflammation being opposed to anti-inflammatory effects, favoring protection against cancer progression. Within the tumor microenvironment, inflammatory cells, belonging both to innate (macrophages) and adaptive (lymphocytes) immune responses, are interconnected with fibroblasts, endothelial cells, adipocytes, and extracellular matrix through cytokines, chemokines and adipocytokines. Under the influence of transcriptional regulators (such as Nuclear Factor-kappa B, mitogen-activated protein kinases, or Phosphoinositide-3 kinase/protein kinase-B), oncogenes connected to the different subtypes of TC promote their farthermost proliferative effect on the tumor microenvironment. Future studies will be necessary to understand the connections between thyroid autoimmunity and cancer, also in order to design a tailored therapy for TC patients with AITD.
Topics: Animals; Autoimmunity; Humans; Neoplasms; Risk Factors; Thyroid Diseases; Thyroid Gland; Tumor Microenvironment
PubMed: 31158464
DOI: 10.1016/j.semcancer.2019.05.019 -
Frontiers in Immunology 2022
Topics: Humans; Autoimmune Diseases; Autoimmunity
PubMed: 36591245
DOI: 10.3389/fimmu.2022.1092469 -
Autoimmunity Reviews Dec 2016Psoriasis is one of the most common chronic inflammatory human skin diseases. Though clinically well characterized, the exact etiological and pathogenic mechanisms are... (Review)
Review
Psoriasis is one of the most common chronic inflammatory human skin diseases. Though clinically well characterized, the exact etiological and pathogenic mechanisms are still not known in detail. Current knowledge indicates distinct overlap to other inflammatory as well as autoimmune disorders. However, the one or more relevant autoantigens could not be characterized so-far. On the other side, several autoimmune diseases were shown to be associated with psoriasis. In addition, serological autoimmune phenomena, namely diverse circulating specific autoantibodies could be demonstrated in the past. A matter of current debate is if psoriasis is a primary autoimmune disease or secondarily evolving into autoimmunity as seen in other chronic inflammatory diseases. Related to this aspect is the concept of autoinflammation versus autoimmunity where psoriasis shares mechanisms of both entities. Though T-cells remain among the most important cellular players in the pathogenesis of psoriasis and current therapeutic strategies successfully target these cells or their products irrespective of these concepts, autoimmunity if relevant will add to the treatment armamentarium by using protective and prophylactic antigen-specific modalities.
Topics: Autoantigens; Autoimmunity; Humans; Immunity, Innate; Psoriasis
PubMed: 27639838
DOI: 10.1016/j.autrev.2016.09.004 -
Best Practice & Research. Clinical... Jan 2020An adjuvant is an immunological or pharmacological substance or group of substances that can be added to a given agent to enhance its effect in terms of efficacy,... (Review)
Review
An adjuvant is an immunological or pharmacological substance or group of substances that can be added to a given agent to enhance its effect in terms of efficacy, effectiveness and potency. Different mechanisms have been hypothesized underlying the action of the adjuvant, including boosting immune (innate and adaptive) response: this generally results in sparing the necessary amount of the agent and can potentially reduce the frequency of the needed number of therapeutic interventions. Adjuvants can be commonly found in vaccines, immunization products, mineral oils, cosmetics, silicone breast implants and other therapeutic/medical devices, being usually safe and effective. However, in a fraction of genetically susceptible and predisposed subjects, the administration of adjuvants may lead to the insurgence of serious side-effects, called "autoimmune/inflammatory syndrome by adjuvants" (ASIA) or Shoenfeld's syndrome. The present review is aimed at focusing on the "endocrine pebbles" of the mosaic of autoimmunity and of the ASIA syndrome, collecting together 54 cases of sub-acute thyroiditis, 2 cases of Hashimoto's thyroiditis, 11 cases of primary ovarian failure/primary ovarian insufficiency, 13 cases of autoimmune diabetes type 1, and 1 case of autoimmune adrenal gland insufficiency occurred after exposure to adjuvants.
Topics: Adjuvants, Immunologic; Autoimmune Diseases; Autoimmunity; Diabetes Mellitus, Type 1; Drug-Related Side Effects and Adverse Reactions; Endocrine System Diseases; Genetic Predisposition to Disease; Humans; Risk Factors; Syndrome
PubMed: 32265102
DOI: 10.1016/j.beem.2020.101412 -
Frontiers in Immunology 2022
Topics: Humans; Antigen Presentation; Autoimmunity; Aminopeptidases; Immune System Diseases
PubMed: 36311705
DOI: 10.3389/fimmu.2022.1055152 -
Handbook of Clinical Neurology 2016Considering the diversity and numbers of targets expressed on the estimated 500 billion glia and slightly less numerous but more diverse neurons, if any channel,... (Review)
Review
Considering the diversity and numbers of targets expressed on the estimated 500 billion glia and slightly less numerous but more diverse neurons, if any channel, receptor or protein on such a cell can be the target of the immune system, we need only imagine the possibilities. As those before us looked to the heavens and ultimately walked on the moon, we need to recognize the potential implications of autoimmune neurology - a new subspecialty in neurology that has truly launched! Its importance cannot be overstated as many of the disorders now recognized as autoimmune are treatable and reversible, representing a shift from the traditional view held by many in the lay and medical community that neurologists diagnose but don't treat! In this introductory chapter we provide a brief over-view of how the field developed, tabulate the authors and contents of the individual topics covered in each chapter, and describe some of the on-going challenges of the field.
Topics: Animals; Autoantibodies; Autoimmune Diseases of the Nervous System; Autoimmunity; Humans; Neurology
PubMed: 27112668
DOI: 10.1016/B978-0-444-63432-0.00001-3