- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
Dysregulovaný zápalový proces zohráva významnú úlohu nielen pri rozvoji chronickej plakovej psoriázy, ale je aj hlavným patogenetickým mechanizmom pri vzniku generalizovanej pustulárnej psoriázy a ďalších zriedkavých pustulárnych foriem choroby. Kľúčovými hráčmi v tomto procese sú cytokíny interleukín (IL)-1β, IL-6, faktor nekrotizujúci nádory (TNF), IL-12/23, IL-17A a najmä IL-36. Príčinou ich nadmernej aktivity alebo tvorby sú u niektorých pacientov s generalizovanou pustulárnou psoriázou mutácie v génoch, ktoré kódujú molekuly podieľajúce sa na inhibícii pôsobenia IL-36 (IL-36Ra) alebo na vnútrobunkovej zápalovej signalizácii (CARD14, AP1S3). Poznatky o patologickej úlohe zápalových cytokínov pri vzniku pustulárnych foriem psoriázy našli svoje uplatnenie aj v ich biologickej liečbe pomocou monoklonových protilátok, ktoré neutralizujú pôsobenie IL-12/23, IL-17A, TNF či IL-1β. Ako nádejné sa ukazujú aj monoklonové protilátky proti receptoru pre interleukín 36, ktoré už majú úspešne za sebou prvé fázy klinických skúšok a momentálne sa testuje ich dlhodobá účinnosť, bezpečnosť a tolerovateľnosť.
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.
- Publikační typ
- abstrakt z konference MeSH
Infiltration of immune cells into CNS is one of the essential events in multiple sclerosis (MS) development. Adhesion molecules like the intercellular adhesion molecule 1 (ICAM-1) play critical role in this process. Therefore, the ICAM1 gene containing two important single-nucleotide polymorphisms (SNPs) belongs to candidate loci with possible involvement in MS susceptibility and/or severity. The objective of our case-control study was to analyze the association of two functional ICAM1 polymorphisms rs1799969 (or G241R) and rs5498 (or K469E) with susceptibility to MS and evaluate their influence on the age at disease onset, severity, neurological disability and progression rate. Two hundred forty-eight MS subjects (mean 39.2 years) and 208 age-matched controls (mean 35.6 years) were involved in the study. Genotyping of ICAM1 rs1799969 and rs5498 SNPs was performed by PCR-RFLP. Presence of the rs3135388 polymorphism tagging the major MS risk allele HLA-DRB1*15:01 allele was determined as well. Our analysis revealed no statistically significant association of ICAM1 polymorphisms with risk of MS development in the Slovak population. Stratification of study cohorts by gender, age at onset and presence of the HLA-DRB1*15:01 risk allele showed only moderate changes. Correlation of clinical findings as age at onset, Kurtzke Expanded Disability Status Scale, Multiple Sclerosis Severity Score and progression index with ICAM1 genotypes in MS patients revealed no significant association; however, patients with earlier onset of MS showed slightly higher frequencies of the homozygous G allele at rs5498 in comparison to other genotypes (P = 0.04), suggesting that GG carriers tend to induce MS at an earlier age.
- MeSH
- alely MeSH
- dospělí MeSH
- genetická predispozice k nemoci MeSH
- genotyp MeSH
- HLA-DRB1 řetězec genetika MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé středního věku MeSH
- lidé MeSH
- mezibuněčná adhezivní molekula-1 genetika MeSH
- mladý dospělý MeSH
- roztroušená skleróza genetika MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Slovenská republika MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference 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
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
