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Mechanisms responsible for sex bias in the prevalence of autoimmune diseases
Ráček, Vojtěch ; Daňková, Pavlína (advisor) ; Ciferská, Hana (referee)
Studies have shown that women typically have stronger immune responses than men. This can also make them more susceptible to autoimmune diseases, with females comprising 80% of autoimmune patients. In women, one X chromosome is epigenetically silenced through a process called X chromosome inactivation. However, some immune-related genes located on the X chromosome, such as TLR7 and CD40L, may escape this silencing process in certain cells or tissues. This can result in a sex-biased expression that contributes to the development and susceptibility of autoimmune diseases like lupus, rheumatoid arthritis, and Sjögren's syndrome. Another interesting factor that explains this sex bias is lncRNA XIST, which is a primary regulator of the inactivation process. It plays a crucial role in lupus development and creates an XIST ribonucleoprotein complex with proteins that help establish a repressed chromatin state on the inactivated chromosome. Importantly, many of these proteins are autoantigens in various autoimmune diseases and may serve as clinical markers for the diagnosis of these conditions. While microbiome and sexual hormones also play important roles, the focus remains primarily on XIST RNA and escape genes. Keywords: autoimmune disease, sex bias, X chromosome, escape genes, lncRNA XIST, sexual...
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Molecular mechanisms of cfDNA effects
Hříbková, Natálie ; Daňková, Pavlína (advisor) ; Škubica, Patrik (referee)
The biological role of free circulating DNA is currently being investigated mainly in terms of the etiology of autoimmune conditions and cancer. It appears that the role of cfDNA of nuclear or mitochondrial origin in interacting with receptors of the innate immune system is quite complex and cfDNA is thus involved in a variety of molecular mechanisms such as the spread of cancer metastasis, induction of autophagy and triggering of inflammatory processes. Knowledge of the specific pathways in which cfDNA is involved in the development of these pathologies seems to be crucial, especially in terms of selecting and targeting appropriate therapies. This paper provides a framework for the knowledge on the interaction of cfDNA with receptors of the innate immune system, the induction of immunological signaling pathways and the possible consequences that these molecular pathways may have in the body. Key words: cfDNA, TLR9, cGAS/STING, AIM2, autoimmune disease, biomarker, cancer
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Vitamin D and its functions
De Brito, Christina ; Kočovský, Pavel (advisor) ; Máčová, Ludmila (referee)
Vitamin D is known for its role in the regulation of the metabolism of minerals in the body. Its deficiency is mainly associated with rickets and osteomalacia, characterized by defects in bone growth and development. However, the limits of this hormone's action extend much further. It can influence the differentiation of immune cells, thereby regulating the immune response and cell proliferation. After the discovery of its immunoregulatory functions, vitamin D became a hot candidate for the treatment of autoimmune diseases, such as multiple sclerosis, systemic lupus erythematosus, or diabetes mellitus. Furthermore, vitamin D was found to exhibit a suppressive effect on cancer cells. Vitamin D deficiency is a risk factor associated with the development of encephalomyelitis, schizophrenia, autism, and cardiovascular diseases. Currently, vitamin D analogs are being developed that are just as effective but do not affect calcium metabolism, thus eliminating the toxic effect of high doses of vitamin D. Key words: vitamin D3, 25-hydroxyvitamin D3, 25(OH)D3, cholecalciferol, 1α,25-dihydroxyvitamin D3, 1,25(OH)2D3, calcitriol, immunity, immunoregulatory function, vitamin D deficiency, autoimmune disease
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Case Study of Physiotherapy Treatment of a Patient with Diagnosis Guillain-Barré syndrom
Martinovičová, Miriam ; Nováková, Tereza (advisor) ; Kučerová, Ilona (referee)
Thesis title: Case Study of Physiotherapy Treatment of a Patient with Diagnosis Guillain-Barré syndrome. Author: Miriam Martinovičová Supervisors: PhDr. Tereza Nováková, Ph.D Aim: To examine and better understand the autoimmune disease - inflammatory demyelinating polyradiculoneuropathy, and the subsequent rehabilitation care. Methods: Thesis consists of two parts - a theoretical part and a case study. The subject of the case study is a 53-year-old male patient who has inflammatory demyelinating polyradiculoneuropathy. The case study is composed of the anamnesis of the patient, initial kinesiological examination, final kinesiological examination, and therapeutic procedures the patient underwent. The theoretical part contains basic theoretical knowledge, such as the epidemiology, origin, clinical picture, diagnostic methods, treatment options, including GBS rehabilitation options. The patient showed improvements after the therapy program. The aim of this thesis has been achieved. Keywords: Inflammatory demyelinating polyradiculoneuropathy, Guillain-Barré syndrome, Autoimmune disease, Physiotherapy
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Epigenetické regulace u autoimunitních onemocnění se zaměřením na revmatoidní artritidu
Horková, Veronika ; Daňková, Pavlína (advisor) ; Hušáková, Markéta (referee)
Exact cause of rheumatoid arthritis, as well as other autoimmune diseases has not been identified yet. In last twenty years, epigenetics showed a new face of immune system. DNA methylation, modification of histones - proteins around which DNA is wrapped, or interference of small RNA sequences - microRNAs, these all are heritable changes outside the DNA sequence that provide another component involved in autoimmunity. Presented epigenetic mechanisms alter gene expression and thus facilitate production of pro- inflammatory factors leading to autoimmune reactions. Moreover, genes regulating apoptosis are also frequently targeted by epigenetic modifications. Not only these mechanisms provide another level of immune defense, they also explain higher female susceptibility to autoimmune diseases and the influence of environment on pathogenesis of these diseases.
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Study of interleukin 37 and its role in rheumatoid arthritis
Jandová, Romana ; Šenolt, Ladislav (advisor) ; Krulová, Magdaléna (referee)
Dysregulation between pro- and anti-inflammatory cytokines activity in rheumatoid arthritis (RA) contributes to immune dysregulation, chronic inflammation and subsequent joint destruction. Interleukin-37 (IL-37) has been described as an anti-inflammatory cytokine in several autoimmune diseases. The main aim of this work was to determine the levels of IL-37 in serum and synovial fluid (SF) of RA patients and to compare them with the levels in patients with osteoarthritis (OA) and further explore the association of IL-37 with disease activity and other clinical parameters. Subsequent goal was to study its anti-inflammatory function on RA synovial fibroblasts and describe other cells types of synovial tissue contributing to its production. IL-37 levels were detected using enzyme-linked immunosorbent assay (ELISA). Synovial fibroblasts were stimulated by lipopolysaccharide (LPS) and recombinant IL-37 (rIL-37). The levels of studied genes were detected by PCR. Synovial tissues and immune cells were visualized by immunohistochemical and by immunofluorescence staining. We found increased levels of IL-37 in SF of patients with RA in comparison to OA patients. There was a significant correlation between serum and SF levels of IL-37. RA as well as OA patients showed increased levels of IL-37 in serum than in...
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Case study of physiotherapy treatment of patient with diagnosis systemic lupus erythematosus
Mrázková, Tereza ; Nováková, Tereza (advisor) ; Taušová, Eva (referee)
Title: Case study of physiotherapy treatment of patient with diagnosis systemic lupus erythematosus Objective: A summary of theoretical background, study of comprehensive rehabilitation methodology, proposal of therapy and evaluation of its effect in a patient with diagnosis systemic lupus erythematosus. Methods: The Review of literature and the case study were made during practice in Institute of Rheumatology in Prague from 5. to 30. 1. 2015. It is devided into two parts. Theoretical part summarizes definition, etiology, epidemiology, diagnostics, clinical manifestation, therapy and use of physiotherapy in diagnosis systemic lupus erythematosus. The case study is presented in the special part. Therapeutical approach was prescribed according to the medical history and physical examination and its effect was assessed using kinesiology analysis at the end of the study. Results: The pain of the patient substantialy decreased, she has no more breathing problems and lying in horizontal position is also no longer a problem, the quality of sleep enhanced, the body posture and balance were positively enfluenced and range of motion and stabilization ability of spine improved. Therapeutic methods were chosen appropriately and stated goals of physiotherapy were fulfilled. Keywords: systemic lupus...
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Maternal and fetal microchimerism.
Hynková, Marie ; Tlapáková, Tereza (advisor) ; Pačes, Jan (referee)
Microchimerism is defined as the presence of small amount of genetically distinct cells in one individual. It most often arises during pregnancy and breastfeeding. It can also arise from blood transfusion or organ transplantation. During pregnancy there occurs a bidirectional migration of cells through the placenta between the mother and the fetus. Cells which are transferred during pregnancy and breastfeeding can persist in the offspring until adulthood. During breastfeeding, a big number of immune cells is transferred to the offspring via mother's milk. These cells protect the offspring against pathogens and are involved in modulation of its immune system. Fetal cells persist in mother organism even decades after giving birth and can have long-lasting effect on mother's health condition. These fetal cells can help to regenerate mother's damaged tissues, but they can also contribute to the development of serious autoimmune diseases.
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The Mechanism of Pathogenesis of Experimental Autoimmune Uveitis and Possilbilities of Their Regulation
Klímová, Aneta ; Heissigerová, Jarmila (advisor) ; Pitrová, Šárka (referee) ; Holáň, Vladimír (referee)
Introduction:Uveitis in an ocular inflammation affecting mostly people of working age. Uveitis is responsible for severe visual impairment despite of expanding new therapeutics. The animal models of uveitis were established, because the wide clinical variability of uveitis limits the studies in human medicine. The goal our project was to establish a reproducible model of experimental autoimmune uveitis in Czech Republic, and further on this model to observe the frequency of CD3+ and F4/80+ cells in retina, to assess the influence of microbial environment on intensity of intraocular inflammation and to test the therapeutical possibilities. Material and methods: The C57BL/6J mice were immunized by retinal antigen (IRBP 1-20, interphotoreceptor retinoid binding protein), enhanced by complete Freund's adjuvant and pertussis toxin and mild posterior autoimmune uveitis was induced. The mice were bred in conventional and germ-free (gnotobiotic) conditions. The uveitis intensity was evaluated in vivo biomicroscopically and post mortem histologically on hematoxylin eosin stained sections according to the standard protocol. The histological eye specimen were analyzed also by imunohistochemisty and by flow cytometry. Each experiment was performed for 35 days. The conventional mice with uveitis were treated...
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