PURPOSE: We investigated associations between neovascular age-related macular degeneration (AMD) and rs10490924 polymorphism of ARMS2 gene (age-related maculopathy susceptibility 2), rs1061170 polymorphism of gene for complement factor H (CFH), rs2230199 polymorphism of gene for complement component C3 and rs11200638 polymorphism of gene for serine protease high-temperature requirement A1 (HTRA1) in the Czech population. METHODS: We analysed samples of DNA from 307 patients diagnosed with neovascular form of late AMD (average age: 73.7 ± 7.7 years) and 191 control subjects, recruited from patients awaiting cataract surgery (average age, 73.6 ± 8.7 years). RESULTS: HTRA1, CFH and ARMS2 genes polymorphisms were found to be related to neovascular AMD in the Czech population. All analysed polymorphisms were statistically significantly associated with neovascular AMD, with stronger associations in females than in males. In whole group, CC genotype of CFH gene polymorphism, TT genotype of ARMS2 gene polymorphism and AA genotype of HTRA1 gene polymorphism showed the greatest risk for neovascular AMD with odds ratios equal to 8.43, 10.07, 9.83, respectively (p < 0.0001). Only CG polymorphism of C3 gene showed statistically significant risk for neovascular AMD. In addition, we observed an association between waist circumference and neovascular AMD in both sexes, which further suggests the significance of excessive abdominal fat as a risk factor of AMD. We found a statistically significant association between polymorphisms in HTRA1, CFH and ARMS2 genes and neovascular AMS in the Czech population. The association was stronger in females than in males. CONCLUSION: We demonstrated a relationship between neovascular AMD and genes for HTRA1, CFH, ARMS2 and C3 in Czech population. To our knowledge, the relationship between these polymorphisms and neovascular AMD in Czech population has never been investigated before.

• MeSH
• abdominální obezita komplikace   MeSH
• jednonukleotidový polymorfismus MeSH
• komplement - faktor H genetika   MeSH
• komplement C3 genetika   MeSH
• lidé MeSH
• makulární degenerace genetika   MeSH
• proteiny genetika   MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• serinová proteasa HTRA1 genetika   MeSH
• sexuální faktory MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Ticks possess components of a primordial complement system that presumably play a role in the interaction of the tick immune system with tick-borne pathogens and affect their transmission. Here we characterized a novel complement component, tagged as IrC2/Bf, from the hard tick Ixodes ricinus, the principal vector of Lyme disease in Europe. IrC2/Bf is a multi-domain molecule composed of 5-7 CCP modules, varied by alternative splicing, followed by a von Willebrand factor A domain and a C-terminal trypsin-like domain. The primary structure and molecular architecture of IrC2/Bf displays the closest homology to the C3-complement component convertases described in horseshoe crabs. The irc2/bf gene is mainly expressed in the tick fat body associated with the trachea and, as determined by western blotting, the protein is present in low amounts in tick hemolymph. Expression of irc2/bf mRNA was significantly up-regulated in response to the intra-hemocoelic injection of the yeast Candida albicans and all tested Borrelia sp. strains (B. burgdorferi NE5264, B. burgdorferi CB26, B. garinii MSLB, B. afzelii CB43), but was not affected by injection of model Gram-negative and Gram-positive bacteria or the aseptic injection control. In-line with these results, RNAi-mediated silencing of irc2/bf inhibited phagocytosis of B. afzelii and C. albicans but not the other bacteria. Tissue expression profiles, specific responses to microbial challenges, and patterns of phagocytic phenotypes upon RNAi silencing observed for IrC2/Bf match well with the previously reported characteristics of I. ricinus C3-related molecule 1 (IrC3-1). Therefore we presume that IrC2/Bf functions as a convertase in the same complement activation pathway protecting ticks against yeast and Borrelia infection.

• MeSH
• aktivace komplementu MeSH
• Borrelia burgdorferi imunologie   MeSH
• Candida albicans imunologie   MeSH
• fagocytóza MeSH
• hemocyty imunologie   mikrobiologie   MeSH
• hmyzí proteiny genetika   metabolismus   MeSH
• infekce přenášené vektorem MeSH
• interakce hostitele a patogenu MeSH
• kandidóza imunologie   MeSH
• klíště imunologie   MeSH
• komplement C3 genetika   metabolismus   MeSH
• lidé MeSH
• lymeská nemoc imunologie   MeSH
• malá interferující RNA genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

C3 glomerulopatie představuje nově definovanou, vzácnou klinickou jednotku se závažnou prognózou. Symptomatologie je variabilní, diagnostika je založena na výsledku imunofluorescenčního vyšetření z renální biopsie, komplexní vyšetření komplementového systému a genetické vyšetření chorobu potvrdí. Hlavní renální histologický nález je izolovaná akumulace depozit C3 bez protilátek. Prezentujeme kazuistiky dvou pacientek se stejnou diagnózou a relativně odlišným průběhem onemocnění, jedna pacientka je heterozygotním nosičem vzácné (p.A353V) a běžné (varianta MCPggaac haplotyp) mutace.

C3 glomerulopathy is a differentially, diagnostically newly defined rare clinical entity with poor prognosis. Symptomatology is variable, the diagnosis is based on the results of immunofluorescent evaluation of renal biopsy, and the disease is confirmed by genetic testing and complete examination of the complement system. The accumulation of isolated C3 deposits without antibodies is a key histological finding. We report two female patients with the same diagnosis and a relatively different course of disease. One patient is a heterozygous carrier of rare (p.A353V) and common (MCPggaac haplotype) mutation.

• Klíčová slova
• C3 glomerulopatie,
• MeSH
• adenektomie MeSH
• adherence pacienta MeSH
• alternativní dráha komplementu MeSH
• antibakteriální látky MeSH
• biopsie MeSH
• faryngitida diagnóza   farmakoterapie   MeSH
• glomerulonefritida diagnóza   farmakoterapie   patologie   MeSH
• glukokortikoidy MeSH
• hematurie MeSH
• imunosupresivní léčba MeSH
• inhibitory ACE terapeutické užití   MeSH
• komplement C3 analýza   fyziologie   genetika   MeSH
• kyselina mykofenolová terapeutické užití   MeSH
• ledviny anatomie a histologie   patologie   MeSH
• lidé MeSH
• mladiství MeSH
• peniciliny terapeutické užití   MeSH
• prednison terapeutické užití   MeSH
• předškolní dítě MeSH
• proteinurie MeSH
• Streptococcus agalactiae patogenita   MeSH
• tonzilektomie MeSH
• tonzilitida diagnóza   chirurgie   terapie   MeSH
• vulvovaginitida diagnóza   farmakoterapie   MeSH
• vzácné nemoci MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH
• práce podpořená grantem MeSH

Ticks are important ectoparasites and vectors of multiple human and animal diseases. The obligatory hemophagy of ticks provides a formidable route for parasite transmission from one host to another. Parasite survival inside the tick relies on the ability of a pathogen to escape or inhibit tick immune defenses, but the molecular interactions between the tick and its pathogens remain poorly understood. Here we report that tick genomes are unique in that they contain all known classes of the α(2)-macroglobulin family (α(2)M-F) proteins: α(2)-macroglobulin pan-protease inhibitors, C3 complement components, and insect thioester-containing and macroglobulin-related proteins. By using RNA interference-mediated gene silencing in the hard tick Ixodes ricinus we demonstrated the central role of a C3-like molecule in the phagocytosis of bacteria and revealed nonredundant functions for α(2)M-F proteins. Assessment of α(2)M-F functions in a single organism should significantly contribute to the general knowledge on the evolution and function of the complement system. Importantly, understanding the tick immune mechanisms should provide new concepts for efficient transmission blocking of tick-borne diseases.

• MeSH
• alfa-makroglobuliny genetika   MeSH
• Chryseobacterium imunologie   patogenita   MeSH
• fagocytóza genetika   MeSH
• genom imunologie   MeSH
• genomika MeSH
• hemocyty imunologie   metabolismus   mikrobiologie   patologie   MeSH
• hmyzí proteiny genetika   metabolismus   MeSH
• infekce bakteriemi čeledi Flavobacteriaceae genetika   imunologie   MeSH
• komplement C3 genetika   metabolismus   MeSH
• kultivované buňky MeSH
• lidé MeSH
• malá interferující RNA genetika   MeSH
• molekulární evoluce MeSH
• sekvenční analýza DNA MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND/AIMS: Protocol biopsies offer new possibilities to predict kidney allograft outcome. The aim of this study was to find clinical, laboratory, morphological and molecular predictors of short-term renal graft survival. METHODS: Three-month protocol kidney graft biopsy was carried out on 257 patients. The real-time RT-PCR was used to identify intragraft mRNA expression of several cytokines and chemokines and predictive statistics was performed to find markers connected with the risk of premature graft failure. RESULTS: Compared to patients with normal morphology at 3 months, patients with subclinical rejection including borderline changes had experienced more frequent (p < 0.001) acute rejections before 3-month biopsy, serum creatinine >or=170 micromol/l (p < 0.01), and higher intrarenal expression of RANTES, IP-10 (p < 0.001), C3, CD3, IgJ (p < 0.01) and CD20 (p < 0.05). There was a significant correlation between subclinical rejection and the occurrence of late acute rejection and graft failure at the first year after transplantation. Moreover, higher RANTES and IP-10 expressions in subclinical rejection predicted graft loss at one year after transplantation in the univariate analysis. CONCLUSIONS: Patients with subclinical rejection including borderline changes in 3-month biopsy and particularly those with higher intrarenal expression of RANTES and IP-10 mRNA were found to be at risk for premature kidney graft loss.

• MeSH
• antigeny CD20 genetika   MeSH
• antigeny CD3 genetika   MeSH
• biologické markery MeSH
• biopsie MeSH
• chemokin CCL5 genetika   MeSH
• chemokin CXCL10 genetika   MeSH
• dospělí MeSH
• imunosupresiva terapeutické užití   MeSH
• komplement C3 genetika   MeSH
• kreatinin krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA metabolismus   MeSH
• následné studie MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• prediktivní hodnota testů MeSH
• rejekce štěpu diagnóza   farmakoterapie   epidemiologie   imunologie   MeSH
• rizikové faktory MeSH
• testování histokompatibility MeSH
• transplantace ledvin MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH