Kidney fibrosis is the hallmark of chronic kidney disease (CKD) and is characterized by an imbalanced extracellular matrix (ECM) remodeling. Collagen type III is one of the main ECM components of the interstitial matrix of the kidney. We hypothesized that measuring three biomarkers of collagen type III reflecting different aspects of this protein turnover (C3M, C3C, and PRO-C3) may provide different information about the fibrotic burden in patients with IgA nephropathy (IgAN). We examined a cohort of 134 patients with IgAN. The three collagen type III biomarkers were measured in serum (S) and in urine (U) samples taken on the same day before kidney biopsy was performed. Biopsies were evaluated for interstitial fibrosis and tubular atrophy, according to the Banff and MEST-C scores. S-PRO-C3 and S-C3C correlated with the degree of fibrosis in the biopsy, whereas U-C3M/Cr had an inverse correlation with fibrosis. U-C3M/Cr had the highest discrimination ability for advanced fibrosis, which was maintained after adjustment for the other collagen type III biomarkers, proteinuria, and serum creatinine. The data presented in this study indicate that measuring the different fragments of the same ECM protein and in different matrices provides a variety of information regarding pathological kidney tissue alterations in patients with IgAN.
- MeSH
- Biomarkers MeSH
- Fibrosis MeSH
- Glomerulonephritis, IGA * pathology MeSH
- Collagen Type III MeSH
- Complement C3 analysis MeSH
- Kidney pathology MeSH
- Humans MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Diarrhea-associated hemolytic uremic syndrome is characterized by hemolytic anemia, thrombocytopenia, and acute kidney injury secondary to enteric infection, typically Shiga toxin-producing Escherichia coli. Shiga toxin 2 is able to activate alternative complement pathways; therefore, the aim of the study was to analyze C3 as a predictor of clinical courses in patients with diarrhea-associated hemolytic uremic syndrome. We hypothesized that the patients with increased complement activation at admission suffered from a more severe course. We retrospectively analyzed data of 33 pediatric patients between 1999 and 2015 in the Czech Republic. We tested the association of a C3 concentration with biochemical parameters and the clinical data reflecting the severity of the disease. We found significant correlation between the initial C3 and the duration of renal replacement therapy (r = - 0.62, p = 0.0001) and the initial glomerular filtration rate (r = 0.36, p = 0.026). Patients with C3 < 0.825 g/L needed renal replacement therapy and also had significantly more renal complications (p = 0.015).Conclusion: Based on our study, decreased C3 concentrations can be used as one of the risk factors that can help predict the need for acute dialysis and a more severe course of disease in children with diarrhea-associated hemolytic uremic syndrome. What is Known: • Shiga toxin modulates the function of complement regulatory proteins and thus contributes to complement activation in patients with diarrhea-associated hemolytic uremic syndrome. • Risk factors that can predict the need for acute renal replacement therapy and poor outcome in patients with diarrhea-associated hemolytic uremic syndrome are mainly the combination of oligoanuria, dehydration, leukocytosis, high hematocrit > 23%, and neurological involvement. What is New: • A lowered concentration of C3 at the time of initial presentation of diarrhea-associated hemolytic uremic syndrome was associated with more severe renal failure and the need for renal replacement therapy along with the development of more extra renal complications. • Decreased C3 at admission can predict complicated course of diarrhea-associated hemolytic uremic syndrome.
- MeSH
- Complement Activation immunology MeSH
- Biomarkers blood MeSH
- Renal Dialysis statistics & numerical data MeSH
- Child MeSH
- Hemolytic-Uremic Syndrome complications immunology MeSH
- Infant MeSH
- Complement C3 analysis MeSH
- Kidney physiopathology MeSH
- Humans MeSH
- Child, Preschool MeSH
- Prognosis MeSH
- Diarrhea complications immunology MeSH
- Retrospective Studies MeSH
- Risk Factors MeSH
- ROC Curve MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic 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.
- Keywords
- C3 glomerulopatie,
- MeSH
- Adenoidectomy MeSH
- Patient Compliance MeSH
- Complement Pathway, Alternative MeSH
- Anti-Bacterial Agents MeSH
- Biopsy MeSH
- Pharyngitis diagnosis drug therapy MeSH
- Glomerulonephritis diagnosis drug therapy pathology MeSH
- Glucocorticoids MeSH
- Hematuria MeSH
- Immunosuppression Therapy MeSH
- Angiotensin-Converting Enzyme Inhibitors therapeutic use MeSH
- Complement C3 analysis physiology genetics MeSH
- Mycophenolic Acid therapeutic use MeSH
- Kidney anatomy & histology pathology MeSH
- Humans MeSH
- Adolescent MeSH
- Penicillins therapeutic use MeSH
- Prednisone therapeutic use MeSH
- Child, Preschool MeSH
- Proteinuria MeSH
- Streptococcus agalactiae pathogenicity MeSH
- Tonsillectomy MeSH
- Tonsillitis diagnosis surgery therapy MeSH
- Vulvovaginitis diagnosis drug therapy MeSH
- Rare Diseases MeSH
- Check Tag
- Humans MeSH
- Adolescent MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
- Research Support, Non-U.S. Gov't MeSH
The objective of this study is to assess whether elevation of serum inflammatory markers levels may indicate the progression of clinical impairment in Parkinson's disease (PD) patients. In 47 PD patients, the serum levels of the C3 and C4 part of the complement and Interleukin-6 (IL-6) were measured. The results at baseline and after 2 years were correlated with scales measuring memory, depression, motor symptoms, and quality of life. Patients with higher levels of C3 and C4 at baseline had decreased quality of life, verbal ability, and memory. Patients with higher IL-6 at baseline showed worse depression scores at 2 years. Patients with persistently higher levels of C3 and C4 at 2 years had worse quality of life and memory ability. Uncorrected p values are reported due to the exploratory nature of the study. The results indicate an impact of inflammation on non-motor signs and quality of life in PD. The increase of levels of serum inflammatory biomarkers may indicate the progression of non-motor impairment in PD.
- MeSH
- Biomarkers blood MeSH
- Interleukin-6 blood MeSH
- Complement C4 analysis MeSH
- Complement C3 analysis MeSH
- Middle Aged MeSH
- Humans MeSH
- Longitudinal Studies MeSH
- Parkinson Disease blood immunology MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
INTRODUCTION: Belimumab is a fully humanised mAb against B lymphocyte stimulator (B-LyS). It is the first biological drug licensed and approved by the US FDA and the European Medicines Agency (EMA) for use in combination with standard immunosuppressants in autoantibody-positive systemic lupus erythematosus (SLE). Areas covered: This manuscript evalues the recent data concerning belimumab's safety and clinical effectiveness and its current place in the treatment of SLE. This includes an overview of the recent data coming from the post-hoc analyses of the BLISS trials, real-life experience with belimumab and the accumulating data on its safety. Attention is also paid to the progress made in the identification of predictors of response to belimumab, recent phase I/II/III studies with subcutaneous belimumab, and experience with B cell modulation coming from recent trials with other B cell modulating drugs. Expert opinion: Belimumab currently has its established role in the treatment of patients with SLE with serologic activity and clinical activity namely in mucocutaneous and musculoskeletal domains despite standard of care treatment. Better identification of patients who can benefit from treatment with belimumab is warranted. Data from ongoing studies in lupus nephritis and other data from observational studies are eagerly awaited.
- MeSH
- Antibodies, Antinuclear blood MeSH
- B-Cell Activating Factor immunology MeSH
- Antibodies, Monoclonal, Humanized adverse effects immunology therapeutic use MeSH
- Clinical Trials as Topic MeSH
- Complement C3 analysis MeSH
- Quality of Life MeSH
- Humans MeSH
- Lupus Erythematosus, Systemic drug therapy pathology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Chronický únavový syndrom představuje často se objevující onemocnění zejména v posledních 15 až 20 letech. Ohroženi jsou zejména lidé žijící ve stresu, jedinci s oslabenou imunitou, trpící infekčním onemocněním nebo přetrénovaní sportovci, např. po vysoké zátěži. Ultravytrvalostním během se mohou vychylovat imunitní, fyziologické a biochemické parametry v rámci svého fyziologického rozmezí. Cílem této studie bylo zjistit, zda fyzická zátěž ultravytrvalostních sportovců vybraného závodu poškozuje organismus ve smyslu změny některých parametrů imunitního systému a jaké výchylky od fyziologických hodnot nastávají. Ze vzorků séra ultramaratonců byly na mistrovství ČR v běhu na 100km před závodem i po závodě měřeny čtyři parametry – IgA, IgM, IgG a C3 složka komplementu. U hodnot IgA a IgG je statisticky významně zvýšená hladina po absolvování závodu ve srovnání s jejich hladinou před závodem. Změny parametrů hodnot IgM a C3 složky komplementu nebyly statisticky významné. Hlavní fyziologickou úlohou IgG je aktivace komplementu, rozvoj sekundární imunitní reakce a neutralizace bakteriálních toxinů. IgA jako slizniční imunoglobulin napomáhá imunitním buňkám pohlcovat cizorodé částice, bakterie a toxiny. Při vychýlení hodnot těchto parametrů je imunitní systém více ohrožen různými infekčními onemocně- ními a objevuje se i chronický únavový syndrom.
Chronic fatigue syndrome is a disease detected in recent 15 or 20 years. Overtrained athletes, people living in stress, the ones with disturbed immunity or people suffering from some of the infectious diseases are the most threatened ones. During ultra-long-distance run, human immune, physiological a biochemical parameters drift of their physiological ranges. The values could increase or decrease. The samples of serum of ultramarathon runners, who took part in the National Ultramarathon Mastership, were collected and measured before and after the race. The parameters include IgA, IgM, IgG and C3 part of complement. Statistically important increases in IgA and IgG concentrations after the race were observed. The changes of concentrations of IgM and C3 part of complement was not statistically important. IgG is responsible for the activation of complement, secondary immune reactions and the neutralization of bacterial toxins. IgA in the role of muckal imunoglobulin helps immune cells to swallow heterogenous particles, germs and toxins. Our immune systém is more threatened by heterogenous infectious diseases and even the chronic fatigue syndrome.
- MeSH
- Running physiology MeSH
- Immunoglobulins analysis physiology MeSH
- Immunologic Factors MeSH
- Complement C3 analysis physiology MeSH
- Humans MeSH
- Fatigue Syndrome, Chronic MeSH
- Physical Exertion * physiology immunology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
In vitro fertilization (IVF) is fraught with problems and currently proteomics approaches are being tried out to examine the microenvironment of the follicle in order to assess biological and immunological parameters that may affect its development. Additionally, better understanding of reproductive process may help increase IVF birth rate per embryo transfer and at the same time avoid spontaneous miscarriages or life threatening conditions such as ovarian hyperstimulation syndrome. The primary aim of this study was to search for specific differences in protein composition of human follicular fluid (HFF) and plasma in order to identify proteins that accumulate or are absent in HFF. Depletion of abundant proteins combined with multidimensional protein fractionation allowed the study of middle- and lower-abundance proteins. Paired comparison study examining HFF with plasma/serum from women undergoing successful IVF revealed important differences in the protein composition which may improve our knowledge of the follicular microenvironment and its biological role. This study showed involvement of innate immune function of complement cascade in HFF. Complement inhibition and the presence of C-terminal fragment of perlecan suggested possible links to angiogenesis which is a vital process in folliculogenesis and placental development. Differences in proteins associated with blood coagulation were also found in the follicular milieu. Several specific proteins were observed, many of which have not yet been associated with follicle/oocyte maturation. These proteins together with their regulatory pathways may play a vital role in the reproductive process.
- MeSH
- Electrophoresis, Gel, Two-Dimensional MeSH
- Fertilization in Vitro MeSH
- Follicular Fluid chemistry metabolism MeSH
- Hemolysis MeSH
- Heparan Sulfate Proteoglycans analysis MeSH
- Immunoblotting MeSH
- Clusterin analysis MeSH
- Complement C4 analysis metabolism MeSH
- Complement C3 analysis metabolism MeSH
- Humans MeSH
- Proteome analysis metabolism MeSH
- Reproducibility of Results MeSH
- Cluster Analysis MeSH
- Signal Transduction MeSH
- Chromatography, High Pressure Liquid MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Changes of the selected immunological parameters before and after the speleotherapy are studied. It seems, that CIK and Complement parameters can be effected during the treatment in caves while Ig and LSZ parameters did not show any systematic changes. Details are available in the paper.
- MeSH
- Child MeSH
- Immunoglobulins analysis MeSH
- Antigen-Antibody Complex analysis MeSH
- Complement C4 analysis MeSH
- Complement C3 analysis MeSH
- Complementary Therapies * MeSH
- Humans MeSH
- Muramidase analysis blood MeSH
- Respiratory Tract Diseases immunology therapy MeSH
- Saliva enzymology MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czechoslovakia MeSH
