- MeSH
- Apolipoproteins E genetics adverse effects MeSH
- Epigenesis, Genetic physiology genetics MeSH
- Genes * physiology genetics MeSH
- Complement Factor H genetics adverse effects MeSH
- Humans MeSH
- Macular Degeneration * genetics physiopathology MeSH
- Retinal Drusen pathology MeSH
- Risk MeSH
- Life Style MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Atypical hemolytic uremic syndrome (aHUS), also called complement-mediated hemolytic uremic syndrome (CM-HUS), is a rare disease caused by dysregulation in the alternative complement activation pathway. It is a life-threatening condition causing ischemia of a number of organs, and it typically causes acute kidney injury. This disorder may be triggered by various factors including viral or bacterial infections, pregnancy, surgery, and injuries. In about 60% of cases, the genetic origin of the disease can be identified-commonly mutations affecting complementary factor H and MCP protein. Eculizumab, a monoclonal antibody to the C5 component of the complement, represents the current effective treatment.We describe a case of a young woman with a previous history of polyvalent allergies, who developed atypical hemolytic uremic syndrome after vaccination with mRNA vaccine against SARS-CoV-2. The disease manifested by scleral bleeding, acute renal insufficiency, anemia, and thrombocytopenia. The patient was treated with plasma exchanges without sufficient effect; remission occurred only after starting treatment with eculizumab. Genetic examination showed that the patient is a carrier of multiple inherited risk factors (a rare pathogenic variant in CFH, MCPggaac haplotype of the CD46 gene, and the risk haplotype CFH H3). The patient is currently in hematological remission with persistent mild renal insufficiency, continuing treatment with eculizumab/ravulizumab. By this case report, we meant to point out the need for careful monitoring of people after vaccination, as it may trigger immune-mediated diseases, especially in those with predisposing factors.
- MeSH
- Acute Kidney Injury * complications MeSH
- Atypical Hemolytic Uremic Syndrome * genetics diagnosis MeSH
- COVID-19 * MeSH
- Complement Factor H genetics MeSH
- Complement System Proteins genetics MeSH
- Humans MeSH
- RNA, Messenger MeSH
- Antibodies, Monoclonal MeSH
- SARS-CoV-2 MeSH
- Vaccination adverse effects MeSH
- COVID-19 Vaccines adverse effects MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
- Research Support, Non-U.S. Gov't MeSH
Pathogens possess the ability to adapt and survive in some host species but not in others-an ecological trait known as host tropism. Transmitted through ticks and carried mainly by mammals and birds, the Lyme disease (LD) bacterium is a well-suited model to study such tropism. Three main causative agents of LD, Borrelia burgdorferi, B. afzelii, and B. garinii, vary in host ranges through mechanisms eluding characterization. By feeding ticks infected with different Borrelia species, utilizing feeding chambers and live mice and quail, we found species-level differences in bacterial transmission. These differences localize on the tick blood meal, and specifically complement, a defense in vertebrate blood, and a polymorphic bacterial protein, CspA, which inactivates complement by binding to a host complement inhibitor, Factor H (FH). CspA selectively confers bacterial transmission to vertebrates that produce FH capable of allele-specific recognition. CspA is the only member of the Pfam54 gene family to exhibit host-specific FH-binding. Phylogenetic analyses revealed convergent evolution as the driver of such uniqueness, and that FH-binding likely emerged during the last glacial maximum. Our results identify a determinant of host tropism in Lyme disease infection, thus defining an evolutionary mechanism that shapes host-pathogen associations.
- MeSH
- Bacterial Proteins genetics metabolism MeSH
- Biological Evolution MeSH
- Borrelia burgdorferi genetics growth & development immunology MeSH
- Species Specificity MeSH
- Immune Evasion physiology MeSH
- Host-Pathogen Interactions physiology MeSH
- Ticks MeSH
- Complement Factor H metabolism MeSH
- Quail MeSH
- Humans MeSH
- Lyme Disease immunology transmission MeSH
- Mice MeSH
- Viral Tropism physiology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
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
- Obesity, Abdominal complications MeSH
- Polymorphism, Single Nucleotide MeSH
- Complement Factor H genetics MeSH
- Complement C3 genetics MeSH
- Humans MeSH
- Macular Degeneration genetics MeSH
- Proteins genetics MeSH
- Risk Factors MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- High-Temperature Requirement A Serine Peptidase 1 genetics MeSH
- Sex Factors MeSH
- Case-Control Studies MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
Atypical hemolytic-uremic syndrome (aHUS) is an extremely rare disease, and up to 70% of the patients have a genetic mutation in the encoding components of complement activation or anti-complement factor H autoantibodies. The risk of recurrence after kidney transplantation is 10% to 80%. Eculizumab, a monoclonal antibody that binds complement protein C5, has shown to be highly effective in patients with aHUS; however, there are only few reports on the efficacy and safety of long-term eculizumab treatment in children with recurrent aHUS. Only 3 case reports regard treatment in patients with complement factor H (CFH/CFHR1/CFHR3) hybrid gene. This report presents the efficacy and safety of long-term eculizumab treatment in a child with recurrent aHUS who has been successfully treated with eculizumab for more than 7 years. The patient presented as a 9-year-old with aHUS due to CFH/CFHR1/CFHR3 hybrid gene and received deceased donor kidney transplantation. After the transplantation, he experienced recurrence of aHUS 2 months later. Daily plasma exchanges were ineffective in the transplanted kidney; the patient became anuric and hemodialysis was needed. Eculizumab was started as therapy and led to complete remission of aHUS including restoration of diuresis. Eculizumab has been given as therapy for 7 years. The young patient is in a sustained remission without any adverse events. This patient is only the sixth patient reported with recurrent aHUS due to CFH/CFHR1/CFHR3 hybrid gene and is the patient with the longest remission of recurrent aHUS ever published.
- MeSH
- Complement Activation genetics MeSH
- Atypical Hemolytic Uremic Syndrome drug therapy genetics surgery MeSH
- Time Factors MeSH
- Child MeSH
- Antibodies, Monoclonal, Humanized administration & dosage MeSH
- Complement Factor H genetics MeSH
- Humans MeSH
- Antibodies, Monoclonal administration & dosage MeSH
- Mutation MeSH
- Postoperative Complications drug therapy genetics MeSH
- Recurrence MeSH
- Kidney Transplantation adverse effects MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
INTRODUCTION: In the last 10 years, many studies have been published on the role of the complement system in microcirculation disorders. However, as for the changes of complement components after rheohemapheresis, there is still a lack of detailed data in the literature. Complement changes may play an important role in pathogenesis of some microcirculation disorders, such as age-related macular degeneration and acute hearing loss. The objective of this study was to investigate the effect of rheohemapheresis on the basic complement pathways. PATIENTS AND METHODS: 32 patients were treated with rheohemapheresis, including 16 patients (10 men and 6 women) for age-related macular degeneration (AMD), mean age 69.7 ± 6.06 years (range 62-87 years) and 16 patients (11 men and 5 women) aged 56.4 ± 11.5 (range 34-73 years) for acute hearing loss. RESULTS: Rheohemapheresis led to a significant drop of all three complement-activation pathways in both groups of patients. Moreover, complement factor H was also reduced. CONCLUSION: The observed reduction in all three basic complement activation pathways after rheohemapheresis could be clinically important. The search continues both to find substances which influence complement systems and to develop more effective new drugs that require less frequent administration and that provide improved intraocular therapy for AMD patients.
- MeSH
- Complement Activation * MeSH
- Complement Factor H metabolism MeSH
- Complement System Proteins metabolism MeSH
- Middle Aged MeSH
- Humans MeSH
- Macular Degeneration blood diagnosis immunology therapy MeSH
- Hearing Loss, Sudden blood diagnosis immunology therapy MeSH
- Hearing Loss, Sensorineural blood diagnosis immunology therapy MeSH
- Hemorheology * MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Blood Component Removal methods MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
This study presents the binding of ovine factor H (fH) by various serotypes of Borrelia and simultaneously correlates their complement resistance to sheep serum. Affinity ligand binding assay was employed to study the binding of borrelial proteins to ovine recombinant fH and its truncated forms (short consensus repeat, SCR 7 and SCRs 19-20). From a repertoire of 17 borrelial strains, only two strains showed affinity to sheep fH. A ~28-kDa protein of Borrelia burgdorferi sensu stricto (B. burgdorferi s.s., strain SKT-2) bound full-length fH as well as SCRs 19-20. This fH-binding protein was further identified as complement regulator-acquiring surface protein of B. burgdorferi (BbCRASP-1) by MALDI-TOF analysis. Surprisingly, a ~26-kDa protein of Borrelia bissettii (DN127) showed affinity to full-length fH but not to SCR 7 and SCRs19-20. In complement sensitivity assay, both strains-SKT-2 and DN127-were resistant to normal sheep serum. Significant complement resistance of two Borrelia garinii strains (G117 and T25) was also observed; however, none of those strains was able to bind sheep fH. Our study underscores the need of further exploration of fH-mediated evasion of complement system by Borrelia in domestic animals.
- MeSH
- Bacterial Proteins chemistry genetics immunology MeSH
- Borrelia classification genetics immunology isolation & purification MeSH
- Kinetics MeSH
- Complement Factor H chemistry immunology MeSH
- Lyme Disease immunology microbiology veterinary MeSH
- Molecular Sequence Data MeSH
- Sheep Diseases immunology microbiology MeSH
- Sheep MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
Úvod: Cílem naší práce je definovat potenciální roli a přínos testu BTA TRAK při dispenzarizaci pacientů s Ta a T1 nádory močového měchýře. Soubor a metodika: Do studie bylo zařazeno 81 nemocných s primárním uroteliálním karcinomem močového měchýře kategorie Ta a T1 léčených transuretrální resekcí (TUR). Pacienti byli sledováni obvyklým způsobem pomocí pravidelných cystoskopických kontrol. Moč na stanovení BTA TRAK testu byla odebrána před vstupní TUR a dále před každou kontrolní cystoskopií. Hodnota BTA TRAK testu byla korelována s výsledkem endoskopického vyšetření. Ke korelaci jsme použili nejen absolutní hodnotu testu, ale i dva indexy, které uvažují hodnotu testu před vstupní TUR (Index 1), respektive před první kontrolní cystoskopií (Index 2). Výsledky: V průběhu sledování bylo provedeno 252 cystoskopií u 81 pacientů, recidiva nádoru byla zachycena v 80 případech (31,7 %) u 47 nemocných. Průměrné hodnoty BTA TRAK, Indexu 1 a Indexu 2 byly vyšší u pacientů s recidivou onemocnění než u pacientů bez recidivy. Při použití prahové hodnoty nastavené na 95% specificitu dosáhla senzitivita BTA TRAK 27,5 %. Použití Indexu 1 ani Indexu 2 nevedlo ke zvýšení senzitivity. Při prahové hodnotě 0,91 U/ml dosáhla senzitivita 90 % (metoda zachytí všechny invazivní a špatně diferencované tumory) a specificita 28,8 %. Závěr: Průměrná hodnota BTA TRAK testu byla signifikantně vyšší u pacientů s recidivou uroteliálního nádoru než u nemocných bez recidivy. U vybraných pacientů s nízkou hodnotou markeru lze uvažovat o prodloužení intervalu do příští cystoskopické kontroly.
Introduction: Our objective was to define the possible role and benefit of the BTA TRAK test in the surveillance of patients with Ta and T1 bladder tumours. Material and methods: Eighty-one patients with primary Ta and T1 urothelial cell carcinoma of the bladder treated by transurethral resection (TUR) were included in the study. The patients were followed routinely with cystoscopy at regular intervals. Urine samples for BTA TRAK testing were collected prior to initial transurethral resection and then prior to each check cystoscopy. The value of the BTA TRAK test was correlated to the result of the endoscopic investigation. Correlation was performed using the absolute value of the test as well as two indexes which take into account the value of the test prior to both the initial TUR and the first check cystoscopy (Index 1 and Index 2, respectively). Results: During follow-up, 252 cystoscopies were performed in 81 patients with 80 cases (31.7 %) of tumour recurrence detected in 47 patients. The mean values of BTA TRAK, Index 1, and Index 2 were higher in patients with recurrence of disease as compared to those without recurrence. When a cutoff value set at 95 % specificity was used, BTA TRAK sensitivity reached 27.5 %. The use of Index 1 and Index 2 did not result in an increase in sensitivity. At a cutoff value of 0.91 U/ml, sensitivity and specificity reached 90 % (all invasive and poorly differentiated tumours are detected) and 28.8 %, respectively. Conclusion: The mean value of BTA TRAK was significantly higher in patients with recurrence of urothelial carcinoma than in those without recurrence. In selected patients with a low level of the marker, prolonging of the interval until the next check cystoscopy may be considered.
- MeSH
- Cystoscopy statistics & numerical data utilization MeSH
- Research Support as Topic MeSH
- Complement Factor H isolation & purification urine MeSH
- Humans MeSH
- Monitoring, Immunologic methods utilization MeSH
- Biomarkers, Tumor urine MeSH
- Urinary Bladder Neoplasms diagnosis urine prevention & control MeSH
- Urothelium physiopathology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Comparative Study MeSH
