The dysregulated inflammatory process not only plays an important role in the development of chronic plaque psoriasis but also is a major pathogenetic mechanism behind the generalized pustular psoriasis (GPP) and other rare pustular forms of the disease. The key players in this process are the cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF), IL-12/23, IL-17A and especially IL-36. Their excessive activity or production in some GPP patients is due to mutations in genes that encode molecules involved in inhibiting the action of IL-36 (IL-36Ra) or in intracellular inflammatory signaling (CARD14, AP1S3). Knowledge about the pathological role of inflammatory cytokines in the development of pustular forms of psoriasis has also found application in their biological therapy with monoclonal antibodies that neutralize the action of IL-12/23, IL-17A, TNF or IL-1β. Other promising agents are monoclonal antibodies against the interleukin 36 receptor, which have already successfully gone through the first phases of clinical trials and are currently being tested for their long-term efficacy, safety and tolerability.

• Klíčová slova
• autoinflammatory disease, biological therapy, generalized pustular psoriasis, interleukin 36, spesolimab,
• MeSH
• akutní nemoc MeSH
• chronická nemoc MeSH
• guanylátcyklasa MeSH
• lidé MeSH
• membránové proteiny MeSH
• psoriáza * farmakoterapie   MeSH
• signální adaptorové proteiny CARD MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• CARD14 protein, human MeSH Prohlížeč
• guanylátcyklasa MeSH
• membránové proteiny MeSH
• signální adaptorové proteiny CARD MeSH

MAIT cells are a separate cell population differentiating in the thymus. They are mostly present in the peripheral blood, liver, intestine, and lungs, less often in other tissues, and infrequently in the lymph nodes. The presentation molecules for MAIT cells are MR1 proteins. They are evolutionarily conserved and non-polymorphic, resemble class I HLA molecules, and are expressed by all cell types. They present bacterial and yeast vitamin metabolites which arise during the synthesis of vitamin B2. The effector functions of MAIT cells are promoted through cytokine synthesis. They also act cytotoxically, directly killing infected or tumour cells. MAIT cells may also play a role in pathological processes. Their involvement in the development of rheumatoid arthritis, systemic lupus erythematosus, autoimmune diabetes mellitus, Crohn's disease, and bronchial asthma has been demonstrated. In practical terms, MAIT cells are very sensitive to therapeutic doses of glucocorticoids. Treatment of patients with BA or chronic obstructive pulmonary disease with glucocorticoids increases their susceptibility to pneumonia, especially when caused by Streptococcus pneumoniae.

• Klíčová slova
• MAIT cells, presentation molecule MR1, role in disease pathogenesis, susceptibility to glucocorticoids,
• MeSH
• lidé MeSH
• MAIT buňky * imunologie   MeSH
• vedlejší histokompatibilní antigeny MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• vedlejší histokompatibilní antigeny MeSH

Crohns disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders of the intestine, also called inflammatory bowel diseases (IBD), which are not caused by pathogenic microorganisms but result from non-specific inflammatory processes in the bowel. IBD are polygenic diseases, as evidenced by the genome-wide association studies (GWAS), which have discovered more than 200 genes or genetic regions to be associated with IBD. Some of them are specific for CD or UC; however, there are 110 overlapping genes. In the pathogenesis of CD, activation of adaptive immunity mediated by TH1, TH17, or TH1/TH17 cells is induced because of disturbances in the mechanisms of innate immunity and autophagocytosis. By comparison, the major events that trigger autoimmune processes in UC are an increased translocation of commensal bacteria into the submucosa because of loose inter-epithelial connections with subsequent activation of ILC2, TH9, TH2, and NKT cells. Knowledge of the pathogenesis of a disease enables an effective therapy, which is especially true for biological therapy. It is noteworthy that monoclonal antibodies directed against the major protagonists underlying both CD and UC have failed. It points to the complexity of immunopathologic processes that run in both diseases. One can suppose that a blockade of one inflammatory pathway is circumvented by an alternative pathway. TNF is the principal pro-inflammatory cytokine that plays a major role in CD and UC as well. It was therefore decided to treat IBD patients with anti-TNF monoclonal antibodies, infliximab or adalimumab. Approximately one half of the CD patients and one third of the UC patients respond to this treatment.

• Klíčová slova
• Crohn - ulcerative colitis - autophagocytosis - autoantibodies - T cells subsets - innate lymphoid cells - anti-TNF treatment.,
• MeSH
• adalimumab terapeutické užití   MeSH
• antiflogistika terapeutické užití   MeSH
• biologická terapie * MeSH
• celogenomová asociační studie MeSH
• Crohnova nemoc * genetika   imunologie   patofyziologie   terapie   MeSH
• infliximab terapeutické užití   MeSH
• lidé MeSH
• ulcerózní kolitida * genetika   imunologie   patofyziologie   terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adalimumab MeSH
• antiflogistika MeSH
• infliximab MeSH

Multiple sclerosis (MS) is an inflammatory autoimmune disease occurring in genetically sensitive individuals. As migration of immune cells into the CNS is facilitated by the Very Late Antigen 4 (VLA-4) integrin molecule, the VLA4 gene may be considered as a plausible candidate genetic risk factor for susceptibility to MS. Therefore, the objective of our study was to investigate the association between two genetic polymorphisms located in the VLA4 gene and the risk of multiple sclerosis. One hundred seventeen MS patients and 165 control subjects from Slovakia were genotyped for VLA4 gene SNP polymorphisms at positions 269 (C/A) and 3061 (A/G). The same study cohorts were also genotyped for the rs3135388 polymorphism tagging the HLA-DRB1*15:01 allele, which is a known genetic factor associated with susceptibility to develop MS in many populations. Our findings show for the first time that the rs3135388 polymorphism is a strong risk factor for MS in the Slovak population. Investigation of the VLA4 gene polymorphisms revealed a significantly higher frequency of the 3061AG genotype in MS patients compared to the controls (P ≤ 0.05). We suggest that the 3061AG polymorphic variant is an independent genetic risk factor for MS development in our population as it was significantly associated with this disease. The association was also confirmed after applying multivariate logistic-regression analysis adjusted for gender, age and HLA-DRB1*15:01 positivity as possible influencing factors.

• MeSH
• alely MeSH
• dospělí MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci * MeSH
• HLA-DRB1 řetězec genetika   MeSH
• integrin alfa4beta1 genetika   MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• lidé MeSH
• roztroušená skleróza genetika   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Slovenská republika MeSH
• Názvy látek
• HLA-DRB1 řetězec MeSH
• integrin alfa4beta1 MeSH

Type 1 diabetes mellitus (T1 DM) is caused by autoimmune-mediated and idiopathic beta-cell destruction of the pancreatic islets of Langerhans resulting in absolute insulin deficiency. Susceptibility to T1 DM is influenced by both genetic and environmental factors. It is generally believed that in genetically susceptible individuals, the disease is triggered by environmental agents, such as viral infections, dietary factors in early infancy, or climatic influences. Many candidate genes for diabetes have been reported; those within the Major Histocompatibility Complex being among the most important. The most common autoantigens are insulin, glutamic acid decarboxylase 65, insuloma-associated antigen 2, and zinc transporter ZnT8. The destruction of beta-cells is mediated mainly by cellular mechanisms; antibodies only seem to reflect the ongoing autoimmune processes and are not directly involved in the tissue damage. They, however, appear prior to the onset of insulin deficiency which makes them suitable for use in the prevention of the disease.

• Klíčová slova
• T, and NKT cells., autoantigens - autoantibodies - HLA alleles - insuline - B,
• MeSH
• autoantigeny genetika   imunologie   MeSH
• diabetes mellitus 1. typu genetika   imunologie   MeSH
• Langerhansovy ostrůvky imunologie   MeSH
• lidé MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• autoantigeny MeSH

Systemic lupus erythematosus (SLE) is an organ non-specific autoimmune disorder, with multiple immunopathogenic mechanisms being implicated in its development. The most conspicuous feature of the disease is an exaggerated synthesis of various types of autoantibodies, followed by the formation of immune complexes that deposit in tissues and elicit an inflammatory response. Apart from antibodies, dendritic cells, T cells and cytokines are substantially involved in the pathogenesis of SLE and class I interferons seem to play a crucial role. SLE is a genetically determined disease. HLA system and complement system genes, apoptosis regulating genes and IgG Fc-gamma receptor genes are among the multiple genes implicated in SLE. The role of hormones, both estrogen and progesterone, in SLE activity has been reported. Some monoclonal antibodies have recently proved effective in the treatment of SLE.

• MeSH
• lidé MeSH
• systémový lupus erythematodes * genetika   imunologie   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• přehledy MeSH

Balb/c mice were immunized with the recombinant fusion protein gD1/313 (FpgD1/313 representing the ectodomain of HSV-1 gD), with the non-pathogenic ANGpath gE-del virus, with the plasmid pcDNA3.1-gD expressing full-length gD1 and with the recombinant immediate early (IE) HSV-1 protein ICP27. Specific antibodies against these antigens (as detected by ELISA) reached high titers with the exception of the DNA vaccine. High-grade protection against challenge with the virulent strain SC16 was found following immunization with the pcDNA3.1-gD plasmid and with the gE-del virus. Medium grade, but satisfactory protection developed after immunization with the FpgD1/313 and minimum grade protection was seen upon immunization with the IE/ICP27 polypeptide. A considerable response of peripheral blood cells (PBL) and splenocytes in the lymphocyte transformation test (LTT) was found in mice immunized with FpgD1/313, with the pcDNA3.1-gD plasmid and with the live ANGpathgE-del virus. For lymphocyte stimulation in vitro, the FpgD1/313 antigen was less effective than the purified gD1/313 polypeptide (cleaved off from the fusion protein); both proteins elicited higher proliferation at the 5 microg per 0.1 mL dose than at the 1 microg per 0.1 mL dose. The secretion of Th type 1 (TNF, IFN-gamma and IL-2) and Th type 2 (IL-4 and IL-6) cytokines was tested in the medium fluid of purified PBL and splenocyte cultures; their absolute values were expressed in relative indexes. The PBL from FpgD1/313 immunized mice showed increased secretion of both T(H)1 (TNF) as well as T(H)2 (IL-4) cytokines (7-10-fold, respectively). Splenocytes from FpgD1/313 immunized mice showed a significant (23-fold) increase in IL-4 production.

• MeSH
• aktivace lymfocytů MeSH
• buněčné linie MeSH
• cytokiny biosyntéza   imunologie   MeSH
• imunizace * MeSH
• krevní buňky imunologie   MeSH
• kultivované buňky MeSH
• lidé MeSH
• lidský herpesvirus 1 genetika   imunologie   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• protilátky virové krev   MeSH
• Simplexvirus imunologie   MeSH
• T-lymfocyty imunologie   MeSH
• vakcína proti viru herpes simplex aplikace a dávkování   imunologie   MeSH
• virové proteiny genetika   imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• cytokiny MeSH
• protilátky virové MeSH
• vakcína proti viru herpes simplex MeSH
• virové proteiny MeSH

Type 1 diabetes mellitus (DM 1A) is an autoimmune disease belonging to the most frequent chronic diseases of the childhood and young adults. DM 1A results from immune-mediated destruction of the insulin-producing beta cells of the pancreas. It is a genetically determined disease and many genes or genetic regions were found to be associated with its induction. In addition to the insulin-dependent diabetes mellitus 1 (IDDM1) gene, which marks the HLA region, and IDDM2 which marks the insulin gene, significant associations of DM 1A to other IDMM genes or genetic regions we reported. We shortly review recent achievements in the field, and the state of current knowledge.

• MeSH
• antigen CTLA-4 MeSH
• CD antigeny imunologie   metabolismus   MeSH
• diabetes mellitus 1. typu genetika   metabolismus   MeSH
• diferenciační antigeny imunologie   metabolismus   MeSH
• genetická predispozice k nemoci * MeSH
• HLA antigeny genetika   MeSH
• inzulin genetika   metabolismus   MeSH
• lidé MeSH
• tyrosinfosfatasa nereceptorového typu 1 MeSH
• tyrosinfosfatasa nereceptorového typu 22 MeSH
• tyrosinfosfatasy metabolismus   MeSH
• životní prostředí MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antigen CTLA-4 MeSH
• CD antigeny MeSH
• CTLA4 protein, human MeSH Prohlížeč
• diferenciační antigeny MeSH
• HLA antigeny MeSH
• inzulin MeSH
• PTPN22 protein, human MeSH Prohlížeč
• tyrosinfosfatasa nereceptorového typu 1 MeSH
• tyrosinfosfatasa nereceptorového typu 22 MeSH
• tyrosinfosfatasy MeSH

OBJECTIVES: Several associations between HLA complex and diabetes mellitus type IA were found in various groups of patients of Caucasoid population. This study was therefore prompted to be conducted in Slovak population, since any such has not yet been performed in Slovak population. METHODS: Patients suffering from DM-1A originated from all regions of Slovakia. Their age ranged from 1 to 42 years; but the criterion for including the subject to the study was the definition of diagnosis in older patients before their age of 15 (Table 1). The diagnosis was set up according to internationally accepted criteria. A total of 460 patients was typed for HLA-DQB1 alleles, among them 97 also for HLA-DQA1 and 146 for HLA-DRB1 alleles. HLA-typing was performed by a PCR-SSP method. Control group consisted of 196 (DQA), 143 (DQB1) and 130 (DRB1) unrelated blood donors aged 19-55 years old irrespective of their age or sex. The data obtained were expressed in a 2 x 2 contingency table and statistical significance was calculated by the Fisher exact test. RESULTS: Among 11 HLA-DQB1 alleles tested DOB1*0302 was the most frequent in DM-1A patients (30.33% vs. 5.59% in healthy subjects (HS), followed by DQB1*0201 (22.93% vs. 12.94%, respectively). In contrast, the frequency rate of DQB1*0301 (10.66% vs. 24.48%), DOB1*0602 (2.17% vs. 10.14%) and DQB1*0603 (2.5% vs. 8.39 %) were decreased in DM-1A patients. Out of 14 DQA1 alleles the highest occurrence rate showed DQA1*0301 (30.93% vs. 17.09) and DQA1*0501 (34.02% vs. 25.76%), while DQA1*0102 (8.76% vs. 16.58%) and DQA1*0201 (6.18 % vs. 13.51%7), respectively, were found to be the least frequent. Among 13 HLA-DRB1 alleles tested, the most common occurrence rates showed DRB1*03 (26.37% vs. 9.62%) and DRB1*04 (7.19% vs. 14.23%), while the least frequent alleles were DRB 1*15 (2.74% vs. 12.31%), DRB1*07 (7.19% vs. 14.23%), and DRB1*11 (2.74% vs. 20.38%). The alleles DQB1*0302 and DQA1*0301, respectively, were present in the same individual in all DRB1*04 positive patients, suggesting that they belong to the haplotype. Similar situation was observed with the alleles DQB1*0201, DQA1*0501, and DRB*0301, respectively, forming the second HLA haplotype so characteristic for DM1A.

• MeSH
• diabetes mellitus 1. typu genetika   imunologie   MeSH
• dítě MeSH
• dospělí MeSH
• frekvence genu * MeSH
• genetická predispozice k nemoci MeSH
• genetická vazba MeSH
• geny MHC třídy II * MeSH
• HLA-D antigeny klasifikace   genetika   MeSH
• HLA-DQ alfa řetězec MeSH
• HLA-DQ antigeny genetika   MeSH
• HLA-DQ beta řetězec MeSH
• HLA-DR antigeny genetika   MeSH
• HLA-DRB1 řetězec MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• referenční hodnoty MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Geografické názvy
• Slovenská republika MeSH
• Názvy látek
• HLA-D antigeny MeSH
• HLA-DQ alfa řetězec MeSH
• HLA-DQ antigeny MeSH
• HLA-DQ beta řetězec MeSH
• HLA-DQA1 antigen MeSH Prohlížeč
• HLA-DQB1 antigen MeSH Prohlížeč
• HLA-DR antigeny MeSH
• HLA-DRB1 řetězec MeSH

The ability of the innate immune system to recognize and respond to microbial components has been largely attributed to the family of TLRs. They are able to discriminate among distinct molecular patterns associated with microbial components. Recognition of microbial products by TLRs results in induction of innate immunity mechanisms as well in development of antigen-specific adaptive immune responses. Some of TLR ligands start to be used to enhance immune defence mechanisms in fighting infections or malignancies. On the contrary, others were shown to be involved in immunopathogenesis of autoimmune disorders such as SLE.

• MeSH
• alfa-defensiny MeSH
• autoimunita MeSH
• defensiny imunologie   MeSH
• intracelulární signální peptidy a proteiny fyziologie   MeSH
• lidé MeSH
• přirozená imunita MeSH
• signální transdukce MeSH
• toll-like receptory fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• alfa-defensiny MeSH
• defensiny MeSH
• intracelulární signální peptidy a proteiny MeSH
• toll-like receptory MeSH