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Expert Review of Clinical Immunology Nov 2021Autoimmune lymphoproliferative syndrome (ALPS) is a rare disorder of immune dysregulation characterized by derangements in first apoptosis signal-mediated apoptosis and... (Review)
Review
INTRODUCTION
Autoimmune lymphoproliferative syndrome (ALPS) is a rare disorder of immune dysregulation characterized by derangements in first apoptosis signal-mediated apoptosis and elevations in CD3TCRαβCD4CD8 'double negative' T cells. As our understanding of this pleomorphic disorder expands, the importance of molecular diagnosis is ever more apparent due to the growing number of disorders that may present with overlapping initial symptoms, but for which there is an ever-increasing list of therapeutic options.
AREAS COVERED
This review will cover the current understanding of the molecular biology and pathophysiology of ALPS as well as describe some of the overlapping syndromes in order to better demonstrate the importance of establishing the correct diagnosis.
EXPERT OPINION
Going forward, international, multicenter collaboration to fully characterize ALPS and the ALPS-like disorders, including with particular focus on defining the defects for those patients with undefined ALPS, is important to both continue to improve our understanding of this disorder and to drive patient care forward to provide the best outcomes. Additionally, it is probably time to re-convene an international expert panel to re-define diagnostic criteria taking into consideration the most recent available data in order to optimize patient care.
Topics: Apoptosis; Autoimmune Diseases; Autoimmune Lymphoproliferative Syndrome; Humans; Multicenter Studies as Topic; Receptors, Antigen, T-Cell, alpha-beta; T-Lymphocytes; fas Receptor
PubMed: 34503378
DOI: 10.1080/1744666X.2021.1978842 -
Current Allergy and Asthma Reports Jun 2020Cogan's syndrome (CS) is a rare systemic vasculitis that can severely affect vision and hearing, which may also have significant systemic effects. Early recognition of... (Review)
Review
PURPOSE OF REVIEW
Cogan's syndrome (CS) is a rare systemic vasculitis that can severely affect vision and hearing, which may also have significant systemic effects. Early recognition of this autoimmune disorder and intervention can minimize disabling and irreversible damage.
RECENT FINDINGS
This article will review the varying clinical presentations of CS and emerging information of systemic disease associated with CS. We will also review recently published promising treatment outcomes using immune modulating medications. As our framework for recognizing the markers of CS and the associated systemic disorders expands, more effective guidelines and treatment options may emerge.
Topics: Autoimmune Diseases; Cogan Syndrome; Humans
PubMed: 32548646
DOI: 10.1007/s11882-020-00945-1 -
Autoimmunity Reviews Jan 2024Fibromyalgia (FM) is a multifactorial syndrome which includes not only widespread pain and stiffness, now recognized as major symptoms, but also numerous other somatic,... (Review)
Review
Fibromyalgia (FM) is a multifactorial syndrome which includes not only widespread pain and stiffness, now recognized as major symptoms, but also numerous other somatic, emotional, and neuropsychic manifestation. The lack of specific validated biological and instrumental biomarkers has made FM a condition of unexplained medical significance, and its pathophysiology remains controversial and subject to debate. The current hypothesis regarding the pathogenesis of FM proposes that its development is influenced by various mechanism, including genetic predisposition, stressful life events, inflammatory processes, and cognitive-emotional factors. However, despite the extensive research conducted to date, the available data do not provide a clear understanding of the pathogenesis of FM. In this article, we report the opposing viewpoints of two leading experts who debate the question of whether FM is an autoimmune disease, based on scientific data regarding this condition. Both perspectives are discussed and the latest evidence on the pathophysiology of FM is reported to provide a comprehensive understanding of this complex syndrome.
Topics: Humans; Fibromyalgia; Syndrome; Biomarkers; Autoimmune Diseases; Genetic Predisposition to Disease
PubMed: 37634681
DOI: 10.1016/j.autrev.2023.103424 -
Giornale Italiano Di Dermatologia E... Dec 2019Alopecia areata (AA) is an organ-specific autoimmune disorder that targets anagen phase hair follicles. The course is unpredictable and current available treatments have...
Alopecia areata (AA) is an organ-specific autoimmune disorder that targets anagen phase hair follicles. The course is unpredictable and current available treatments have variable efficacy. Nowadays, there is relatively little evidence on treatment of AA from well-designed clinical trials. Moreover, none of the treatments or devices commonly used to treat AA are specifically approved by the Food and Drug Administration. The Italian Study Group for Cutaneous Annexial Disease of the Italian Society of dermatology proposes these Italian guidelines for diagnosis and treatment of Alopecia Areata deeming useful for the daily management of the disease. This article summarizes evidence-based treatment associated with expert-based recommendations.
Topics: Alopecia Areata; Autoimmune Diseases; Evidence-Based Medicine; Hair Follicle; Humans; Italy
PubMed: 31578836
DOI: 10.23736/S0392-0488.19.06458-7 -
Rheumatology International Aug 2023Systemic lupus erythematosus (SLE) is a complex autoimmune disorder of unknown etiology. Multifactorial interaction among various susceptible factors such as... (Review)
Review
Systemic lupus erythematosus (SLE) is a complex autoimmune disorder of unknown etiology. Multifactorial interaction among various susceptible factors such as environmental, hormonal, and genetic factors makes it more heterogeneous and complex. Genetic and epigenetic modifications have been realized to regulate the immunobiology of lupus through environmental modifications such as diet and nutrition. Although these interactions may vary from population to population, the understanding of these risk factors can enhance the perception of the mechanistic basis of lupus etiology. To recognize the recent advances in lupus, an electronic search was conducted among search engines such as Google Scholar and PubMed, where we found about 30.4% publications of total studies related to genetics and epigenetics, 33.5% publications related to immunobiology and 34% related to environmental factors. These outcomes suggested that management of diet and lifestyle have a direct relationship with the severity of lupus that influence via modulating the complex interaction among genetics and immunobiology. The present review emphasizes the knowledge about the multifactorial interactions between various susceptible factors based on recent advances that will further update the understanding of mechanisms involved in disease pathoetiology. Knowledge of these mechanisms will further assist in the creation of novel diagnostic and therapeutic options.
Topics: Humans; Lupus Erythematosus, Systemic; Autoimmune Diseases; Epigenesis, Genetic; Risk Factors
PubMed: 37226016
DOI: 10.1007/s00296-023-05346-x -
Nature Reviews. Neuroscience Dec 2019B cells are essential components of the adaptive immune system and have important roles in the pathogenesis of several central nervous system (CNS) diseases. Besides... (Review)
Review
B cells are essential components of the adaptive immune system and have important roles in the pathogenesis of several central nervous system (CNS) diseases. Besides producing antibodies, B cells perform other functions, including antigen presentation to T cells, production of proinflammatory cytokines and secretion of anti-inflammatory cytokines that limit immune responses. B cells can contribute to CNS disease either through their actions in the periphery (meaning that they have an 'outside-in' effect on CNS immunopathology) or following their compartmentalization within the CNS. The success of B cell-depleting therapy in patients with multiple sclerosis and CNS diseases with an autoantibody component, such as neuromyelitis optica spectrum disorder and autoimmune encephalitides, has underscored the role of B cells in both cellular and humoral-mediated CNS conditions. Emerging evidence suggests B cells also contribute to the pathogenesis of neurodegenerative diseases, including Alzheimer disease and Parkinson disease. Advancing our understanding of the role of B cells in neuroinflammatory and neurodegenerative diseases could lead to novel therapeutic approaches.
Topics: Adaptive Immunity; Animals; Autoimmune Diseases; B-Lymphocytes; Central Nervous System Diseases; Humans; Immunosuppressive Agents; Neurodegenerative Diseases
PubMed: 31712781
DOI: 10.1038/s41583-019-0233-2 -
Medicina (Kaunas, Lithuania) Jul 2022The 'Focal Infection Era in Dentistry' in the late 19th and early 20th century resulted in widespread implementation of tooth extraction and limited the progress of... (Review)
Review
The 'Focal Infection Era in Dentistry' in the late 19th and early 20th century resulted in widespread implementation of tooth extraction and limited the progress of endodontics. The theory proposed that bacteria and toxins entrapped in dentinal tubules could disseminate systemically to remote body parts, resulting in many types of degenerative systemic diseases. This theory was eventually refuted due to anecdotal evidence. However, lately there has been increased interest in investigating whether endodontic disease could have an impact on general health. There are reviews that have previously been carried out on this subject, but as new data have emerged since then, this review aims to appraise the available literature investigating the dynamic associations between apical periodontitis, endodontic treatment, and systemic health. The available evidence regarding focal infection theory, bacteraemia and inflammatory markers was appraised. The review also collated the available research arguing the associations of apical periodontitis with cardiovascular diseases, diabetes mellitus, adverse pregnancy outcome and autoimmune disorders, along with the effect of statins and immunomodulators on apical periodontitis prevalence and endodontic treatment prognosis. There is emerging evidence that bacteraemia and low-grade systemic inflammation associated with apical periodontitis may negatively impact systemic health, e.g., development of cardiovascular diseases, adverse pregnancy outcomes, and diabetic metabolic dyscontrol. However, there is limited information supporting the effect of diabetes mellitus or autoimmune disorders on the prevalence and prognosis post endodontic treatment. Furthermore, convincing evidence supports that successful root canal treatment has a beneficial impact on systemic health by reducing the inflammatory burden, thereby dismissing the misconceptions of focal infection theory. Although compelling evidence regarding the association between apical periodontitis and systemic health is present, further high-quality research is required to support and establish the benefits of endodontic treatment on systemic health.
Topics: Autoimmune Diseases; Bacteremia; Cardiovascular Diseases; Diabetes Mellitus; Female; Focal Infection; Humans; Periapical Periodontitis; Pregnancy
PubMed: 35888650
DOI: 10.3390/medicina58070931 -
Journal of Clinical Immunology Jan 2021Ras-associated autoimmune leukoproliferative disorder (RALD) is a clinical entity initially identified in patients evaluated for an autoimmune lymphoproliferative...
Ras-associated autoimmune leukoproliferative disorder (RALD) is a clinical entity initially identified in patients evaluated for an autoimmune lymphoproliferative syndrome (ALPS)-like phenotype. It remains a matter of debate whether RALD is a chronic and benign lymphoproliferative disorder or a pre-malignant condition. We report the case of a 7-year-old girl diagnosed with RALD due to somatic KRAS mutation who progressed to a juvenile myelomonocytic leukemia phenotype and finally evolved into acute myeloid leukemia. The case report prompted a literature review by a search for all RALD cases published in PubMed and Embase. We identified 27 patients with RALD. The male-to-female ratio was 1:1 and median age at disease onset was 2 years (range 3 months-36 years). Sixteen patients (59%) harbored somatic mutations in KRAS and 11 patients (41%) somatic mutations in NRAS. The most common features were splenomegaly (26/27 patients), autoimmune cytopenia (15/16 patients), monocytosis (18/24 patients), pericarditis (6 patients), and skin involvement (4 patients). Two patients went on to develop a hematopoietic malignancy. In summary, the current case documents an additional warning about the long-term risk of malignancy in RALD.
Topics: Adolescent; Adult; Alleles; Autoimmune Diseases; Autoimmune Lymphoproliferative Syndrome; Autoimmunity; Child; Child, Preschool; Combined Modality Therapy; Diagnosis, Differential; Disease Management; Disease Susceptibility; Female; Genetic Predisposition to Disease; Genotype; Humans; Infant; Karyotype; Male; Mutation; Myeloproliferative Disorders; Phenotype; Prognosis; Skin; Treatment Outcome; Young Adult; ras Proteins
PubMed: 33011939
DOI: 10.1007/s10875-020-00883-7 -
Genes Feb 2021Autoimmune thyroid diseases (AITDs), including Hashimoto's thyroiditis (HT) and Graves' disease (GD), are the most common cause of acquired thyroid disorder during... (Review)
Review
Autoimmune thyroid diseases (AITDs), including Hashimoto's thyroiditis (HT) and Graves' disease (GD), are the most common cause of acquired thyroid disorder during childhood and adolescence. Our purpose was to assess the main features of AITDs when they occur in association with genetic syndromes. We conducted a systematic review of the literature, covering the last 20 years, through MEDLINE via PubMed and EMBASE databases, in order to identify studies focused on the relation between AITDs and genetic syndromes in children and adolescents. From the 1654 references initially identified, 90 articles were selected for our final evaluation. Turner syndrome, Down syndrome, Klinefelter syndrome, neurofibromatosis type 1, Noonan syndrome, 22q11.2 deletion syndrome, Prader-Willi syndrome, Williams syndrome and 18q deletion syndrome were evaluated. Our analysis confirmed that AITDs show peculiar phenotypic patterns when they occur in association with some genetic disorders, especially chromosomopathies. To improve clinical practice and healthcare in children and adolescents with genetic syndromes, an accurate screening and monitoring of thyroid function and autoimmunity should be performed. Furthermore, maintaining adequate thyroid hormone levels is important to avoid aggravating growth and cognitive deficits that are not infrequently present in the syndromes analyzed.
Topics: Autoimmune Diseases; Genetic Predisposition to Disease; Graves Disease; Hashimoto Disease; Humans; Pediatrics; Thyroid Gland
PubMed: 33557156
DOI: 10.3390/genes12020222 -
Frontiers in Immunology 2023Autoimmune bullous disease (AIBD) is a severe skin disorder caused by autoantibodies that target intercellular or cell-matrix adhesion proteins. Currently, the preferred... (Review)
Review
Autoimmune bullous disease (AIBD) is a severe skin disorder caused by autoantibodies that target intercellular or cell-matrix adhesion proteins. Currently, the preferred treatment for AIBD involves the use of glucocorticoids or traditional immunosuppressants. Additionally, the utilization of biological agents such as rituximab, omalizumab, and dupilumab is on the rise. However, effectively managing AIBD remains a challenge. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway has been implicated in various inflammatory diseases. In recent years, a range of drugs known as JAK inhibitors, which target this pathway, have been developed. Several studies have explored the efficacy and safety of JAK inhibitors for treating AIBD. Consequently, this review begins by examining the role of the JAK/STAT pathway in AIBD, summarizing the application of different JAK inhibitors in AIBD treatment, and emphasizing the importance of disease management in treating AIBD with JAK inhibitors. Furthermore, it highlights the need for a better understanding of the JAK/STAT pathway's role in AIBD, as well as the effectiveness and safety of JAK inhibitors for treating this disease.
Topics: Humans; Janus Kinase Inhibitors; Janus Kinases; STAT Transcription Factors; Signal Transduction; Autoimmune Diseases; Skin Diseases, Vesiculobullous
PubMed: 37492565
DOI: 10.3389/fimmu.2023.1220887