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The Biochemical Journal Mar 2013H(v) channels (voltage-gated proton channels) are expressed in blood cells, microglia and some types of epithelial cells. In neutrophils H(v) channels regulate the...
H(v) channels (voltage-gated proton channels) are expressed in blood cells, microglia and some types of epithelial cells. In neutrophils H(v) channels regulate the production of reactive oxygen species through regulation of membrane potential and intracellular pH. H(v) channels have also been suggested to play a role in sperm physiology in the human. However, the functions of the Hv channel at the whole-body level are not fully understood. In the present paper we show that Hvcn1 (voltage-gated hydrogen channel 1)-knockout mice show splenomegaly, autoantibodies and nephritis, that are reminiscent of human autoimmune diseases phenotypes. The number of activated T-cells was larger in Hvcn1-deficient mice than in the wild-type mice. Upon viral infection this was remarkably enhanced in Hvcn1-deficient mice. The production of superoxide anion in T-cells upon stimulation with PMA was significantly attenuated in the Hvcn1-deficient mice. These results suggest that H(v) channels regulate T-cell homoeostasis in vivo.
Topics: Animals; Autoimmune Diseases; Humans; Ion Channel Gating; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutrophils; Phenotype; Proton Pumps; Reactive Oxygen Species; Recombinant Proteins; Superoxides; T-Lymphocytes
PubMed: 23231444
DOI: 10.1042/BJ20121188 -
International Journal of Molecular... Oct 2023Autoimmune thyroid disease (AITD) is the most common organ-specific autoimmune disorder clinically presented as Hashimoto thyroiditis (HT) and Graves' disease (GD). The... (Review)
Review
Autoimmune thyroid disease (AITD) is the most common organ-specific autoimmune disorder clinically presented as Hashimoto thyroiditis (HT) and Graves' disease (GD). The pathogenesis of AITD is caused by an inappropriate immune response related to genetic, non-genetic, and environmental factors. Pregnancy is one of the factors that have a great influence on the function of the thyroid gland because of the increased metabolic demand and the effects of hormones related to pregnancy. During pregnancy, an adaptation of the maternal immune system occurs, especially of the innate immune system engaged in maintaining adaptive immunity in the tolerant state, preventing the rejection of the fetus. Pregnancy-related hormonal changes (estrogen, progesterone, hCG) may modulate the activity of innate immune cells, potentially worsening the course of AITD during pregnancy. This especially applies to NK cells, which are associated with exacerbation of HD and GD. On the other hand, previous thyroid disorders can affect fertility and cause adverse outcomes of pregnancy, such as placental abruption, spontaneous abortion, and premature delivery. Additionally, it can cause fetal growth retardation and may contribute to impaired neuropsychological development of the fetus. Therefore, maintaining the thyroid equilibrium in women of reproductive age and in pregnant women is of the highest importance.
Topics: Female; Humans; Pregnancy; Hashimoto Disease; Placenta; Thyroid Diseases; Autoimmune Diseases; Graves Disease; Immunity, Innate
PubMed: 37895126
DOI: 10.3390/ijms242015442 -
Journal of the Neurological Sciences Apr 2015Statin induced necrotizing autoimmune myopathy (SINAM) is a recently characterized entity belonging to the spectrum of statin myotoxicity. It is a more severe form, and... (Review)
Review
Statin induced necrotizing autoimmune myopathy (SINAM) is a recently characterized entity belonging to the spectrum of statin myotoxicity. It is a more severe form, and is usually associated with significant proximal muscle weakness, strikingly elevated creatine kinase levels and persistent symptoms despite statin discontinuation. The characteristic pathological finding is a marked muscle fiber necrosis with minimal or no inflammation on muscle biopsy. SINAM is an autoimmune disorder associated with an antibody against 3-hydroxy-3-methyglutaryl-coenzyme A reductase (HMGCR), and the antibody titer is a useful marker for assessing treatment response. However, anti-HMGCR positive myopathies are also caused by unknown etiologies other than statin exposure, especially in the younger population. SINAM should be promptly recognized as immunosuppressive therapy can improve its clinical outcome significantly. Further research is needed to elucidate its pathogenesis and provide evidence based guidelines for management.
Topics: Autoimmune Diseases; Humans; Hydroxymethylglutaryl CoA Reductases; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscular Diseases; Necrosis
PubMed: 25765229
DOI: 10.1016/j.jns.2015.02.042 -
Clinical Lymphoma, Myeloma & Leukemia Dec 2014Waldenström macroglobulinemia represents a lymphoplasmacytic lymphoma with an indolent clinical course. The existing literature associates this hematologic malignancy... (Meta-Analysis)
Meta-Analysis Review
Waldenström macroglobulinemia represents a lymphoplasmacytic lymphoma with an indolent clinical course. The existing literature associates this hematologic malignancy with various autoimmune disorders. Notwithstanding, these autoimmune conditions have not been comprehensively characterized or systematized to date. As a result, their clinical implications remain largely unknown. The authors offer a comprehensive review of the existing literature on various hematologic and nonhematologic autoimmune disorders documented in the course of Waldenström macroglobulinemia. Whereas some of them are thought to be secondary to a dysfunctional immune response associated with an underlying malignant process, others might be primary and might even play a role in its pathogenesis. Moreover, the observations that personal history and family history of certain autoimmune diseases were associated with an increased risk of subsequent Waldenström macroglobulinemia strengthen further the hypothesis that shared susceptibility genes and chronic antigenic stimulation might predispose individuals to both conditions.
Topics: Autoimmune Diseases; Autoimmunity; Humans; Kidney Diseases; Nervous System Diseases; Pancytopenia; Prevalence; Rheumatic Diseases; Waldenstrom Macroglobulinemia
PubMed: 25022601
DOI: 10.1016/j.clml.2014.04.009 -
Autoimmunity 2015Myasthenia gravis (MG) is a rare autoimmune disease of skeletal muscle endplates. MG subgroup is relevant for comorbidity, but usually not accounted for. MG patients... (Review)
Review
Myasthenia gravis (MG) is a rare autoimmune disease of skeletal muscle endplates. MG subgroup is relevant for comorbidity, but usually not accounted for. MG patients have an increased risk for complicating autoimmune diseases, most commonly autoimmune thyroid disease, systemic lupus erythematosus and rheumatoid arthritis. In this review, we present concomitant autoimmune disorders associated with the different MG subgroups, and show how this influences treatment and prognosis. Concomitant MG should always be considered in patients with an autoimmune disorder and developing new neuromuscular weakness, fatigue or respiratory failure. When a second autoimmune disorder is suspected, MG should be included as a differential diagnosis.
Topics: Animals; Autoantibodies; Autoantigens; Autoimmune Diseases; Autoimmunity; Genetic Predisposition to Disease; Humans; LDL-Receptor Related Proteins; Myasthenia Gravis; Receptor Protein-Tyrosine Kinases; Receptors, Cholinergic; Receptors, Nicotinic; Thymoma
PubMed: 25915571
DOI: 10.3109/08916934.2015.1030614 -
Current Opinion in Neurobiology Oct 1996Rasmussen's encephalitis is a rare progressive pediatric epileptic syndrome. Recent evidence from experimental animals and patients with the disease suggests an... (Review)
Review
Rasmussen's encephalitis is a rare progressive pediatric epileptic syndrome. Recent evidence from experimental animals and patients with the disease suggests an important role for both humoral and cell-mediated immune mechanisms in the pathogenesis of this disease. The glutamate receptor subunit GluR3 may be an important autoantigen in the disease. (This review has been modified from a review published in Current Opinion in Neurology 1996, 9:141-145.)
Topics: Animals; Autoantigens; Autoimmune Diseases; Child; Child, Preschool; Encephalitis; Epilepsy; Humans; Immunity, Cellular; Models, Immunological; Receptors, Glutamate
PubMed: 8937833
DOI: 10.1016/s0959-4388(96)80102-4 -
Arthritis Research & Therapy Feb 2024Sjögren's disease is a heterogeneous autoimmune disorder that may be associated with systemic manifestations such as pulmonary or articular involvement. Systemic... (Review)
Review
Sjögren's disease is a heterogeneous autoimmune disorder that may be associated with systemic manifestations such as pulmonary or articular involvement. Systemic complications have prognostic implications and need to be identified and managed in a timely manner. Treatment should be tailored to the type and severity of organ involvement, ideally based on multidisciplinary evaluation.
Topics: Humans; Sjogren's Syndrome; Autoimmune Diseases
PubMed: 38331820
DOI: 10.1186/s13075-024-03262-4 -
Autoimmunity Reviews Feb 2013Aicardi-Goutieres syndrome (AGS), described by J. Aicardi and F. Goutieres in 1984, is a rare neurological disease with onset in infancy. It is often misdiagnosed as a... (Review)
Review
Aicardi-Goutieres syndrome (AGS), described by J. Aicardi and F. Goutieres in 1984, is a rare neurological disease with onset in infancy. It is often misdiagnosed as a sequela of congenital infection or recognized later. Nowadays almost 200 cases are reported all over the world, most of them collected by the International Aicardi-Goutieres Syndrome Association (IAGSA), founded in Pavia (Italy) in 2000. AGS (MIM 225750) is a genetically-determined encephalopathy characterized by severe neurological dysfunction, acquired microcephaly associated with severe prognosis quoad valetudinem, and less frequently also quoad vitam. Some AGS children also develop some symptoms overlapping with systemic lupus erythematosus (SLE). Intracranial calcification, white matter involvement and brain atrophy revealed on MRI, lymphocytosis and elevated levels of interferon alpha (IFN-α) in the cerebrospinal fluid (CSF) are features of both AGS and congenital viral infection. No evidence of congenital infection at serological exams has ever been found. A genetic etiology was hypothesized since the first descriptions, because of the recurrence in families, and demonstrated some years ago. Nowadays five genes (AGS1-5), if mutated, can be responsible for 90% of the cases. The transmission is autosomal recessive but there are also rare "de novo" autosomal dominant cases. Even if pathogenesis is still almost unknown, it seems that responsible genes are involved in nucleic acid reparation mechanisms and consequently in a secondary activation of innate autoimmunity. The relative lack of precise information on pathogenesis and on the evolution of the disease over time has not yet allowed the creation of codified diagnostic and therapeutic models and programs.
Topics: Age of Onset; Autoimmune Diseases of the Nervous System; Child; Child, Preschool; Humans; Infant, Newborn; Nervous System Malformations; Rare Diseases
PubMed: 22940555
DOI: 10.1016/j.autrev.2012.08.012 -
Annals of Internal Medicine Feb 2005Celiac disease is a common autoimmune disorder that has genetic, environmental, and immunologic components. It is characterized by an immune response to ingested wheat... (Review)
Review
Celiac disease is a common autoimmune disorder that has genetic, environmental, and immunologic components. It is characterized by an immune response to ingested wheat gluten and related proteins of rye and barley that leads to inflammation, villous atrophy, and crypt hyperplasia in the intestine. The disease is closely associated with genes that code for human leukocyte antigens DQ2 and DQ8. Transglutaminase 2 appears to be an important component of the disease, both as a deamidating enzyme that can enhance the immunostimulatory effect of gluten and as a target autoantigen in the immune response. Sensitive and specific serologic tests, including those for anti-transglutaminase antibody, are facilitating fast and noninvasive screening for celiac disease. Thus, they are contributing to a more accurate estimate of the prevalence of the disease and its association with other disorders. Celiac disease is associated with increased rates of anemia, osteoporosis, cancer, neurologic deficits, and additional autoimmune disorders. A gluten-free diet is the mainstay of safe and effective treatment of celiac disease, although its effect on some of the extraintestinal manifestations of the disease remains to be determined.
Topics: Autoantibodies; Autoimmune Diseases; Biomarkers; Celiac Disease; Humans
PubMed: 15710962
DOI: 10.7326/0003-4819-142-4-200502150-00011 -
Critical Reviews in Oncology/hematology Jun 2020Autoimmune disorders are a spectrum of diseases caused by impaired self-tolerance of the immune system. Previous studies underscored the association between autoimmune... (Review)
Review
Autoimmune disorders are a spectrum of diseases caused by impaired self-tolerance of the immune system. Previous studies underscored the association between autoimmune disorders and lymphomas. However, only a few papers studied the exact mechanisms of this association. The effect of IL-2, IL-5, IL-6, IL-10 and TNF-α, contribution of NOTCH, FAS and MHC receptor families, the interplay of various immune cells, and the relation of immunosuppressive agents and development of autoimmune disorders are the proposed mechanisms for this association. Each individual autoimmune disorder associates with particular types of lymphomas and their common pathways are not necessarily similar to other pairs of autoimmune disorder-lymphomas. Thus, the lymphomas susceptibility in various autoimmune disorders could not be investigated through a single pathway. In this review, we demonstrate the association between each pair of autoimmune disorder-lymphoma and the underlying pathways. By clarifying these associations, follow-up plans could be made leading to early diagnosis of lymphomas.
Topics: Autoimmune Diseases; Humans; Immunosuppressive Agents; Lymphoma; Lymphoma, Non-Hodgkin
PubMed: 32353704
DOI: 10.1016/j.critrevonc.2020.102945