Ewa Ziółko

The role of human endogenous retroviruses in the pathogenesis of autoimmune diseases

Summary This paper presents a new, recently formulated theory, which concerns the etiopathological process of autoimmune diseases. This theory takes into account the existence in the human genome, since approximately 40 million years, of so-called human endogenous retroviruses (HERVs), which are transmitted to descendants “vertically” by the germ cells. It was recently established that these generally silent sequences perform some physiological roles, but occasionally become active and influence the development of some chronic diseases like diabetes, some neoplasms, chronic diseases of the nervous system (eg, sclerosis multiplex), schizophrenia and autoimmune diseases. We present a short synopsis of immunological processes involved in the pathogenesis of autoimmune diseases, such as molecular mimicry, epitope spreading and activation of the superantigen. We then focus on experimental findings related to systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome and some diseases of hepar and otorhinal tissues. We conclude the outline of this new model of the development of chronic diseases and indicate the conclusions important for the teaching of the basis of pathology.

Medical and Mental Target Risk Factors for Dementia Prevention

The authors draw attention to two current trends in search for relevant risk factors of cognitive impairment and dementia. They discuss whether the most important risk factors are somatic conditions such as hypertension, hyperlipidemia, obesity, diabetes. The authors indicate arguments, found in the literature that the impaired cognitive performance could be caused partly by the previous cognitive impacts. The authors point out that these two lines of research is combined by the occurrence of depression. They postulate, therefore, that assessment of the health of the older people should take into account the data of stressful events in childhood and youth. Important are also data about current living conditions, social conditions and the current mental and physical activity.

Influence of diet on the risk of developing endometriosis

Endometriosis is a hormone-dependent chronic inflammatory disease characterized by the presence of endometrium beyond the uterine cavity. The disease affects 5-15% of women of child-bearing age, 30-50% of whom suffer from infertility. Understanding the role of dietary factors in the development of endometriosis is critical to development of effective dietary instructions for prevention. Existing studies concerning nutrition and endometriosis suggest that diet is a potentially modifiable risk factor for endometriosis. Fruits and vegetables, fish oils, dairy products rich in calcium and vitamin D, and Omega-3 fatty acids are likely connected with a lower risk of developing endometriosis. Risk factors that increase the risk of endometriosis include consumption of products rich in trans-unsaturated fatty acids, consumption of fats generally, and consumption of beef and other kinds of red meat and alcohol. Currently, there are no clear correlations between par-ticular food products and the risk of endometriosis. Further research is needed in order to fully understand the influence of consumed food products on the risk of development of this disease.

Usefulness of Magnetic Resonance Imaging as a Prognostic Variable in Myelodysplastic Syndromes

Background Myelodysplastic syndromes are clonal disorders of stem cells, characterized by heterogeneous clinical presentation. Hematopoiesis is ineffective, characterized by abnormal differentiation, maturation and survival of hematopoietic cells. Material/Methods The examinations were conducted in the Hematology Ward and the Internal Medicine Ward of the Specialist Hospital No. 1 in Bytom in the years 2006–2011. The study group included 53 patients with diagnosed myelodysplastic syndrome. The results of magnetic resonance imaging (MRI) of the spine were obtained from the medical documentation of patients. Results In the group of patients diagnosed with RT (refractory thrombocytopenia) and in the group diagnosed with RA (refractory anemia), 100% of lumbar spine images in T1- and T2-weighted sequences assessed together showed increased signal intensity. In patients diagnosed with RAEB (refractory anemia with excess blasts), MRI showed decreased signal intensity in 76.5% of subjects in the sequences analyzed together. In the group of patients with increased LDH (lactate dehydrogenase), 22 patients (55%) showed decreased signal intensity in the combined analysis of T1- and T2-weighted sequences. Among transfusion-dependent patients, 20 scans (60.6%) showed decreased signal intensity. Conclusions As the risk category of MDS increases towards high – bad risk, decreased signal intensity is observed in lumbar spine MRI in T1- and T2-weighted images in all studied stratification scales. There is a positive correlation between decreased signal intensity in lumbar spine MRI examinations and increased LDH level in blood serum, as well as dependence on blood product transfusions, especially packed red blood cells.

The role of complement factor H in the pathogenesis of Borrelia infection

Complement factor H (CFH) is one of the most important negative regulators of the alternative pathway of the complement system. It is a glycoprotein belonging to the protein H family, which is synthesized mainly in the liver and is composed into a globular protein consisting of 60 amino acid domains in the serum. It shows specificity for C3b molecule of the complement system present in the serum or bound to the cell surface. It inhibits the steady formation of C3 convertase enzymes and the binding of C2 to C4b and factor B to C3b. It accelerates the decomposition of C2a into C4b and the displacement of Bb from C3b. The present paper discusses the composition, properties and functions of the complement factor and the family it belongs to. The paper focuses in particular on its role in the pathogenesis of an infection caused by the spirochetes of the Borrelia genus. Through binding CFH and other related proteins, bacteria of the Borrelia species inhibit the key effect of the alternative pathway of the complement system - the lysis of spirochete cells dependent on the complements activation. The mechanism enables pathogens to spread in the host organism and facilitates the evolution of the disease. Discovering the immune mechanisms of the infection caused by the spirochetes of the Borrelia genus may allow for implementing a therapy blocking the binding of complement factor H early enough, apart from the standard treatment of the disease.

Expression Profiles of Toll-Like Receptors in the Differentiation of an Infection with Borrelia burgdorferi Sensu Lato Spirochetes

The similarity of Lyme borreliosis to other diseases and its complex pathogenesis present diagnostic and therapeutic difficulties. The changes that occur at the cellular and molecular levels after a Borrelia sp. infection still remain poorly understood. Therefore, the present study focused on the expression of TLR and TLR-signaling genes in human dermal fibroblasts in the differentiation of an infection with Borrelia burgdorferi sensu lato spirochetes. Normal human dermal fibroblasts were cultured with the spirochetes of Borrelia burgdorferi sensu stricto, Borrelia afzelii and Borrelia garinii. Total RNA was extracted from the cells using TRIzol reagent. The analysis of the expression profiles of TLRs and TLR-related genes was performed using commercially available oligonucleotide microarrays of HG-U133A. The GeneSpring 12.0 platform and significance analysis of microarrays were used for the statistical analysis of microarray data. The analyses using the oligonucleotide microarray and QRT-PCR techniques permitted to identify the genes encoding TLR4 and TLR6 as specific for infection with B. afzelii and B. burgdorferi sensu stricto. In turn, TLR3 was only characteristic for an infection with B. burgdorferi sensu stricto. There were no changes in the TLR gene expression after infection with B. garinii. Our findings confirm that Borrelia has a major effect on fibroblast gene expression. Further characterization of changes in gene expression may lead to valuable insights into the role of the toll-like receptor in the pathogenesis of Lyme disease and may provide guidelines for the development of diagnostic markers for an infection with a particular Borrelia genospecies. Moreover, this will help to identify better treatment strategies for Lyme disease.