Waldenströmova makroglobulinémie (WM) patří k low-grade B-lymfomům. Je definována přítomností lymfoplazmocytárního lymfomu v kostní dřeni a monoklonálního imunoglobulinu typu IgM (M-IgM) v séru. Příznaky nemoci, anémie a trombocytopenie, mohou souviset s masou patologických buněk, stejně jako systémové zánětlivé projevy (B-symptomy). Velké spektrum symptomů však způsobuje M-IgM. Koncentrace M-IgM u WM nekoreluje s masou patologických buněk. Spektrum poruch způsobených M-IgM je vzhledem k diverzitě patofyziologických mechanizmů a lokalizaci poškození značně široké. Poškození může vzniknout depozicí kompletní molekuly nebo její části ve formě agregátů, amorfních, krystalických, mikrotubulárních či fibrilárních struktur. M-IgM může také pacienta poškozovat autoprotilátkovou aktivitou namířenou proti antigenům vlastních tkání. Dále může M-IgM tvořit imunitní komplexy a aktivovat komplement. Výjimečně může B buněčný klon indukovat tvorbu cytokinů. Proto je velmi obtížené včas rozpoznat symptomatickou formu WM. V této publikaci popisujeme pacientku poškozenou depozity M-IgM a řetězců lambda. Diskuze je zaměřena na přehled všech forem poškození člověka depozity M-IgM, mezi něž patří i popsaný případ.
Waldenström’s macroglobulinaemia (WM) is a low-grade B-cell lymphoproliferative disorder characterised by an immunoglobulin IgM monoclonal gammopathy and bone marrow infiltration by lymphoplasmacytic lymphoma. Clinical features may be related to the overall disease burden, such as anaemia, thrombocytopenia, and constitutional inflammatory symptoms, or may be directly attributable to the IgM paraprotein. The concentration of monoclonal IgM can vary widely in WM. There is no direct relationship between the concentration of monoclonal immunoglobulin IgM and bone marrow infiltration. The spectrum of monoclonal immunoglobulin IgM-related disorders is large because of the diversity of involved organs and pathogenic mechanisms. Lesions commonly result from the deposition of all or part of the M-IgM as aggregates, amorphous, crystalline, microtubular, or fibrillar forms. Other mechanisms include autoantibody activity against a tissue antigen, formation of immune complexes, and complement activation. In addition, even a small B-cell clone may absorb biologically active molecules or induce cytokine secretion. In our case report, we describe a female patient with monoclonal IgM and lambda liver deposition and we discuss the frequency and variety of disorders caused by deposition of monoclonal IgM and free light chain.
- Klíčová slova
- imunokomplexy,
- MeSH
- amyloid imunologie klasifikace MeSH
- amyloidóza diagnóza imunologie klasifikace patologie MeSH
- hepatomegalie etiologie imunologie MeSH
- imunoglobulin M imunologie krev škodlivé účinky MeSH
- krevní nemoci diagnóza etiologie krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- Waldenströmova makroglobulinemie * diagnostické zobrazování diagnóza imunologie patologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- práce podpořená grantem MeSH
Amyloidosis is a rare metabolic disorder primarily brought on by misfolding of an autologous protein, which causes its local or systemic deposition in an aberrant fibrillar form. It is quite rare for pulmonary tissue to be impacted by amyloidosis; of the three forms it can take when involving pulmonary tissue, nodular pulmonary amyloidosis is the most uncommon. Nodular pulmonary amyloidosis rarely induces clinical symptoms, and most often, it is discovered accidentally during an autopsy or via imaging techniques. Only one case of nodular pulmonary amyloidosis, which manifested as a spontaneous pneumothorax, was found in the literature. In terms of more precise subtyping, nodular amyloidosis is typically AL or mixed AL/AH type. No publications on AH-dominant type of nodular amyloidosis were found in the literature. We present a case of an 81 years-old male with nodular pulmonary AH-dominant type amyloidosis who presented with spontaneous pneumothorax. For a deeper understanding of the subject, this study also provides a review of the literature on cases with nodular pulmonary amyloidosis in relation to precise amyloid fibril subtyping. Since it is often a difficult process, accurate amyloid type identification is rarely accomplished. However, this information is very helpful for identifying the underlying disease process (if any) and outlining the subsequent diagnostic and treatment steps. Even so, it is crucial to be aware of this unit and make sure it is taken into consideration when making a differential diagnosis of pulmonary lesions.
- MeSH
- amyloidóza * komplikace diagnóza patologie MeSH
- lidé MeSH
- plíce diagnostické zobrazování patologie MeSH
- plicní nemoci * komplikace diagnóza patologie MeSH
- pneumotorax * diagnóza etiologie MeSH
- senioři nad 80 let MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- Publikační typ
- kazuistiky MeSH
- přehledy MeSH
Cervikální hlen je viskózní kapalina fungující jako zátka děložního čípku. V cervikálním hlenu můžeme detekovat produkty endometriálních a cervikálních žláz. Cervikální hlen je dále obohacen transudátem pocházejícím z vejcovodů a proteiny pocházející z vaječníků, peritonea a vzdálených tkání. Se zvyšující se hladinou ovariálních estrogenů se vlastnosti cervikálního hlenu mění tak, že umožňují snadnější odběr a zpracování. Z tohoto důvodu jsme vybrali skupinu deseti pacientek léčených kontrolovanou ovariální hyperstimulací pro in vitro fertilizaci v centru asistované reprodukce. Tato studie se zaměřuje na proteomickou charakterizaci cervikálního hlenu a na buněčnou a tkáňovou lokalizaci identifikovaných proteinů. Nejvíce intenzivními proteiny identifikovanými v cervikálním hlenu jsou muciny, ale bylo nalezeno také mnoho méně abundantních proteinů vnitrobuněčného původu. Analýza tkáňových expresí odhalila mnoho proteinů, které jsou kromě tkání ženských reprodukčních orgánů exprimovány také v jiných tkáních a mimo jiné také proteiny specifické pro varlata, játra, placentu, oční sítnici a mozeček. Tato studie dále potvrzuje vhodnost cervikálního hlenu jako zdroje proteomických biomarkerů nejen pro diagnostiku ženského reprodukčního traktu.
Cervical mucus is a viscous fluid functioning as a cervix plug. Products of the endometrial and cervical glands can be detected in the cervical mucus. Cervical mucus is further enriched with transudate originating from the fallopian tubes and proteins originating from the ovaries, peritoneum and distant tissues. With increasing levels of ovarian estrogens, the properties of cervical mucus for possible collection and processing change appropriately. For these reasons, we chose a group of 10 patients treated in the center of assisted reproduction by controlled ovarian stimulation for in vitro fertilization. This study focuses on the proteomic characterization of cervical mucus and localizes the possible sources of the identified proteins. The most abundant proteins were extracellular proteins, mainly mucins; however, most of the identified proteins, present usually in lower quantities, were of intracellular origin. The tissue analysis revealed that proteins from female reproductive organs are also expressed in other tissues in addition to female reproductive organs, but also proteins specific to the testis, liver, placenta, retina, and cerebellum. This study confirms the suitability and high potential of cervical mucus as a source of proteomic biomarkers not only for the diagnosis of the female reproductive tract.
- Klíčová slova
- tkáňové exprese,
- MeSH
- cervikální hlen * chemie MeSH
- klinická studie jako téma MeSH
- lidé MeSH
- proteomika MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
The choroid plexus (ChP) produces and is bathed in the cerebrospinal fluid (CSF), which in aging and Alzheimer's disease (AD) shows extensive proteomic alterations including evidence of inflammation. Considering inflammation hampers functions of the involved tissues, the CSF abnormalities reported in these conditions are suggestive of ChP injury. Indeed, several studies document ChP damage in aging and AD, which nevertheless remains to be systematically characterized. We here report that the changes elicited in the CSF by AD are consistent with a perturbed aging process and accompanied by aberrant accumulation of inflammatory signals and metabolically active proteins in the ChP. Magnetic resonance imaging (MRI) imaging shows that these molecular aberrancies correspond to significant remodeling of ChP in AD, which correlates with aging and cognitive decline. Collectively, our preliminary post-mortem and in vivo findings reveal a repertoire of ChP pathologies indicative of its dysfunction and involvement in the pathogenesis of AD. HIGHLIGHTS: Cerebrospinal fluid changes associated with aging are perturbed in Alzheimer's disease Paradoxically, in Alzheimer's disease, the choroid plexus exhibits increased cytokine levels without evidence of inflammatory activation or infiltrates In Alzheimer's disease, increased choroid plexus volumes correlate with age and cognitive performance.
- Publikační typ
- abstrakt z konference MeSH
Cervical mucus (CM) is a viscous fluid that is produced by the cervical glands and functions as a uterine cervix plug. Its viscosity decreases during ovulation, providing a window for non-invasive sampling. This study focuses on proteomic characterization of CM to evaluate its potential as a non-invasively acquired source of biomarkers and in understanding of molecular (patho)physiology of the female genital tract. The first objective of this work was to optimize experimental workflow for CM processing and the second was to assess differences in the proteomic composition of CM during natural ovulatory cycles obtained from intrauterine insemination (IUI) cycles and in vitro fertilization (IVF) cycles with controlled ovarian hyperstimulation. Proteomic analysis of CM samples revealed 4370 proteins involved in processes including neutrophil degranulation, cellular stress responses, and hemostasis. Differential expression analysis revealed 199 proteins enriched in IUI samples and 422 enriched in IVF. The proteins enriched in IUI were involved in phosphatidic acid synthesis, responses to external stimulus, and neutrophil degranulation, while those enriched in IVF samples were linked to neutrophil degranulation, formation of a cornified envelope and hemostasis. Subsequent analyses clarified the protein composition of the CM and how it is altered by hormonal stimulation of the uterus.
- MeSH
- biologické markery MeSH
- cervikální hlen * MeSH
- fertilizace in vitro MeSH
- lidé MeSH
- proteom MeSH
- proteomika MeSH
- umělá inseminace * MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Anemia is the most common extraintestinal systemic complication of inflammatory bowel disease. Iron deficiency anemia and anemia of chronic disease are among the most frequent types. Intestinal iron absorption is controlled by the activity of ferroportin. Cells with high expression of ferroportin include enterocytes, and also macrophages and hepatocytes. Iron homeostasis is controlled by the hepcidin-ferroportin axis. Hepcidin is a central regulator of iron metabolism and can also serve as a marker of systemic inflammation. During systemic inflammatory response, the synthesis of hepcidin increases, and hepcidin binds to ferroportin and inhibits its activity. Thus, iron is not absorbed from the bowel into the circulation and also remains sequestered in macrophages. Conversely, hepcidin synthesis is suppressed during conditions requiring increased iron intake for enhanced erythropoiesis, such as iron deficiency anemia or hypoxia. Here, ferroportin is not blocked, and iron is actively absorbed into the bloodstream and also released from the stores. Production of hepcidin is influenced by the status of total body iron stores, systemic inflammatory activity and erythropoietic activity. Oral iron therapy is limited in inflammatory bowel diseases due to ongoing gastrointestinal inflammation. It is less effective and may worsen the underlying disease. Therefore, the choice between oral and parenteral iron therapy must be made with caution. Oral iron would be ineffective at high hepcidin levels due to concurrent ferroportin blockage. Contrarily, low levels of hepcidin indicate that oral iron therapy should be successful. An understanding of hepcidin can help in understanding the body's reaction to iron depletion during the inflammatory process.
- MeSH
- anemie etiologie terapie MeSH
- hepcidiny metabolismus MeSH
- idiopatické střevní záněty komplikace MeSH
- lidé MeSH
- proteiny přenášející kationty metabolismus MeSH
- regulace genové exprese MeSH
- železo aplikace a dávkování metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Detection of peptides lies at the core of bottom-up proteomics analyses. We examined a Bayesian approach to peptide detection, integrating match-based models (fragments, retention time, isotopic distribution, and precursor mass) and peptide prior probability models under a unified probabilistic framework. To assess the relevance of these models and their various combinations, we employed a complete- and a tail-complete search of a low-precursor-mass synthetic peptide library based on oncogenic KRAS peptides. The fragment match was by far the most informative match-based model, while the retention time match was the only remaining such model with an appreciable impact--increasing correct detections by around 8 %. A peptide prior probability model built from a reference proteome greatly improved the detection over a uniform prior, essentially transforming de novo sequencing into a reference-guided search. The knowledge of a correct sequence tag in advance to peptide-spectrum matching had only a moderate impact on peptide detection unless the tag was long and of high certainty. The approach also derived more precise error rates on the analyzed combinatorial peptide library than those estimated using PeptideProphet and Percolator, showing its potential applicability for the detection of homologous peptides. Although the approach requires further computational developments for routine data analysis, it illustrates the value of peptide prior probabilities and presents a Bayesian approach for their incorporation into peptide detection.
Exhaled breath condensate is considered a rich source of biomarkers that can provide valuable information for early diagnosis of respiratory and systemic diseases. However, exhaled breath condensate (EBC) consists mainly of water vapor and the concentration of analytes in the exhaled breath condensate sample is very low, close to the detection limit of sensitive methods such as mass spectrometry. Here, we have developed a mass spectrometry-based approach to characterize the EBC proteome. We compared biological and technical replicates of the measured samples, compared the protein profile between individual samples of healthy individuals and described the reproducibility between the three technical replicates of the sample taken. We have found that repeated measurements of samples are reproducible and can increase the number of proteins identified. Analysis led to the detection of 2797 unique proteins in all samples. Based on statistical analysis, it was shown that the 10% difference from the mean is due more to the deviation of the mass spectrometry measurements than to the biological variability of the samples. And second, the change in protein amount below 20% of the average in the case of EBC is due to method variability and should not be considered a significant change in protein expression using label-free mass spectrometry techniques.
- MeSH
- dýchání ústy MeSH
- proteomika metody MeSH
- vydechnutí MeSH
- vzduch * MeSH
- Publikační typ
- přehledy MeSH
AIM: The aim of this study was to compare changes in serum hepcidin levels in paediatric patients with inflammatory bowel disease during therapy and correlate them with markers of iron metabolism, inflammation and type of treatment. METHODS: Children with newly diagnosed Crohn's disease (CD) and ulcerative colitis (UC) were included in this longitudinal study. Blood and stool samples were collected to assess levels of serum hepcidin and markers of iron metabolism parameters and inflammation. The parameters were examined before treatment (baseline levels) and compared with levels in the follow-up period during maintenance therapy (mean follow-up of 39 months after diagnosis). RESULTS: Patients with CD (n = 30) had higher serum hepcidin levels (expressed as a median and interquartile range) at diagnosis than subjects with UC (n = 13). These levels significantly decreased during the follow-up (from 36.5 (11.5-79.6) to 2.1 (0.9-6.7) ng/mL). In contrast, no significant serum hepcidin level changes were observed in the UC patients (5.4 (3.4-16.6) vs. 4.8 (0.9-8.1) ng/mL). While hepcidin level changes correlated with disease activity and inflammatory parameters (erythrocyte sedimentation rate, C-reactive protein), in CD patients, they correlated only with serum iron levels in patients with UC. Biological therapy was accompanied by a significant decrease in C-reactive protein and interleukin-6 compared to conventional anti-inflammatory therapy in CD patients. CONCLUSIONS: Children with CD had higher serum hepcidin levels on diagnosis compared to subjects with UC. During an anti-inflammatory therapy, serum hepcidin decreased in the CD group but remained consistently low in children with UC.
- MeSH
- antiflogistika terapeutické užití MeSH
- biologické markery MeSH
- dítě MeSH
- hepcidiny MeSH
- idiopatické střevní záněty * farmakoterapie MeSH
- lidé MeSH
- longitudinální studie MeSH
- studie případů a kontrol MeSH
- ulcerózní kolitida * farmakoterapie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
