-
Oncotarget Apr 2023Systemic Light chain (AL) amyloidosis is a monoclonal plasma cell proliferative disorder characterized by deposition of amyloidogenic monoclonal light chain fragments... (Review)
Review
Systemic Light chain (AL) amyloidosis is a monoclonal plasma cell proliferative disorder characterized by deposition of amyloidogenic monoclonal light chain fragments causing organ dysfunction. It is a fatal disease and if not diagnosed and treated early can lead to organ failure and potentially death. The renal system along with the cardiovascular system are the most common organs involved but other organs such as gut and liver can be involved as well. The initial evaluation of patients requires confirming the diagnosis with tissue biopsy and staining with Congo red followed by confirmatory typing with mass spectrometry of the Congo red positive tissue. Then establishing the extent of the organs involvement by various staging and biomarkers testing. The treatment options and the tolerability of therapy depend on the disease staging, frailty, and co-morbidities. The autologous hematopoietic cell transplantation (HCT) after high dose melphalan therapy is an effective strategy which is usually done after initial bortezomib induction therapy. Unfortunately, most systemic AL amyloidosis patients are not candidate for HCT due to frailty, old age, multi-organ involvement, renal and heart failure at the time of diagnosis. While it is widely accepted that the patients need to be treated until they achieve complete hematologic response, the maintenance therapy after HCT is not well established in AL amyloidosis. In this review, we report the literature on the latest treatment updates of AL amyloidosis and the ongoing clinical trials highlighting the future treatments.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Congo Red; Frailty; Melphalan; Hematopoietic Stem Cell Transplantation; Paraproteinemias
PubMed: 37185672
DOI: 10.18632/oncotarget.28415 -
Methods in Molecular Biology (Clifton,... 2018Many bacteria can assemble functional amyloid fibers on their cell surface. Most bacterial amyloids contribute to biofilm or other community behaviors where cells...
Many bacteria can assemble functional amyloid fibers on their cell surface. Most bacterial amyloids contribute to biofilm or other community behaviors where cells interact with a surface or with other cells. Bacterial amyloids, like all functional amyloids, share structural and biochemical properties with disease-associated eukaryotic amyloids. The general ability of amyloids to bind specific dyes, like Congo red and Thioflavin T, and their resistance to denaturation have provided useful tools for scoring and quantifying bacterial amyloid formation. Here, we present basic approaches to study bacterial amyloids by focusing on the well-studied curli amyloid fibers expressed by Enterobacteriaceae. These methods exploit the specific tinctorial and biophysical properties of amyloids. The methods described here are straightforward and can be easily applied by any modern molecular biology lab for the study of other bacterial amyloids.
Topics: Bacterial Proteins; Benzothiazoles; Biofilms; Congo Red; Escherichia coli; Escherichia coli Proteins; Protein Multimerization
PubMed: 29886539
DOI: 10.1007/978-1-4939-7816-8_17 -
Brazilian Journal of Medical and... 2022Amyloidoses are a group of disorders in which soluble proteins aggregate and deposit extracellularly in tissues as insoluble fibrils, causing organ dysfunction. Clinical... (Review)
Review
Amyloidoses are a group of disorders in which soluble proteins aggregate and deposit extracellularly in tissues as insoluble fibrils, causing organ dysfunction. Clinical management depends on the subtype of the protein deposited and the affected organs. Systemic amyloidosis may stem from anomalous proteins, such as immunoglobulin light chains or serum amyloid proteins in chronic inflammation or may arise from hereditary disorders. Hereditary amyloidosis consists of a group of rare conditions that do not respond to chemotherapy, hence the identification of the amyloid subtype is essential for diagnosis, prognosis, and treatment. The kidney is the organ most frequently involved in systemic amyloidosis. Renal amyloidosis is characterized by acellular pathologic Congo red-positive deposition of amyloid fibrils in glomeruli, vessels, and/or interstitium. This disease manifests with heavy proteinuria, nephrotic syndrome, and progression to end-stage kidney failure. In some situations, it is not possible to identify the amyloid subtype using immunodetection methods, so the diagnosis remains indeterminate. In cases where hereditary amyloidosis is suspected or cannot be excluded, genetic testing should be considered. Of note, laser microdissection/mass spectrometry is currently the gold standard for accurate diagnosis of amyloidosis, especially in inconclusive cases. This article reviews the clinical manifestations and the current diagnostic landscape of renal amyloidosis.
Topics: Amyloid; Amyloidogenic Proteins; Amyloidosis; Amyloidosis, Familial; Congo Red; Humans; Immunoglobulin Light Chains
PubMed: 36197414
DOI: 10.1590/1414-431X2022e12284 -
Bioscience Reports Jan 2019Staining with Congo Red (CR) is a qualitative method used for the identification of amyloids and in tissue sections. However, the drawbacks and artefacts obtained when... (Review)
Review
Staining with Congo Red (CR) is a qualitative method used for the identification of amyloids and in tissue sections. However, the drawbacks and artefacts obtained when using this dye can be found both and Analysis of scientific data from previous studies shows that CR staining alone is not sufficient for confirmation of the amyloid nature of protein aggregates or for diagnosis of amyloidosis in tissue sections. In the present paper, we describe the characteristics and limitations of other methods used for amyloid studies. Our historical review on the use of CR staining for amyloid studies may provide insight into the pitfalls and caveats related to this technique for researchers considering using this dye.
Topics: Amyloid; Amyloidosis; Benzothiazoles; Coloring Agents; Congo Red; History, 17th Century; History, 18th Century; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Immunohistochemistry; Protein Aggregates; Staining and Labeling
PubMed: 30567726
DOI: 10.1042/BSR20181415 -
Methods in Molecular Biology (Clifton,... 2012Many bacteria can assemble functional amyloid fibers on their cell surface. The majority of bacterial amyloids contribute to biofilm or other community behaviors where...
Many bacteria can assemble functional amyloid fibers on their cell surface. The majority of bacterial amyloids contribute to biofilm or other community behaviors where cells interact with a surface or with another cell. Bacterial amyloids, like all functional amyloids, share structural and biochemical properties with disease-associated eukaryotic amyloids. The general ability of amyloids to bind amyloid-specific dyes, such as Congo red, and their resistance to denaturation have provided useful tools for scoring and quantifying bacterial amyloid formation. Here, we present basic approaches to study bacterial amyloids by focusing on the well-studied curli amyloid fibers expressed by Enterobacteriaceae. These methods exploit the specific tinctorial and biophysical properties of amyloids. The methods described here are straightforward and can be easily applied by any modern molecular biology lab for the study of other bacterial amyloids.
Topics: Amyloid; Blotting, Western; Congo Red; Escherichia coli; Escherichia coli Proteins; Formates; Mutation; Propanols; Protein Multimerization; Protein Structure, Secondary; Protein Structure, Tertiary
PubMed: 22528099
DOI: 10.1007/978-1-61779-551-0_21 -
Prilozi (Makedonska Akademija Na... Jul 2023The glomerulopathies associated with the deposition of extracellular fibrils in the glomeruli are subdivided into Congo red positive (amyloidosis) and Congo red negative...
The glomerulopathies associated with the deposition of extracellular fibrils in the glomeruli are subdivided into Congo red positive (amyloidosis) and Congo red negative (non-amyloidotic glomerulopathies) based on Congo red staining. The non-amyloidotic glomerulopathies are divided into immunoglobulin-derived and non-immunoglobulin-derived glomerulopathies. The immunoglobulin-derived glomerulopathies: fibrillary glomerulopathy (FGn) and immunotactoid glomerulopathy (ITG) are rare glomerulopathies. The diagnosis of fibrillary-immunotactoid glomerulopathy depends on electron microscopy, which shows the presence of microfibrils in the glomeruli. The microfibrils in FGn are randomly arranged with diameters less than 30 nm. The microfibrils in ITG are larger than 30 nm with a visible lumen (microtubules), focally arranged in parallel bundles. Patients with fibrillary-immunotactoid glomerulopathy present with proteinuria (usually in the nephrotic range), microscopic hematuria, arterial hypertension, and chronic kidney disease that progresses to kidney failure over months to years. Currently, there are no guidelines for the treatment of fibrillary-immunotactoid glomerulopathy, although immunotactoid glomerulopathy could be associated with underlying hematologic disorders with the need for clone-directed therapy.
Topics: Humans; Congo Red; Kidney Diseases; Kidney Glomerulus; Glomerulonephritis; Proteinuria
PubMed: 37453107
DOI: 10.2478/prilozi-2023-0030 -
Acta Biochimica Polonica Mar 2019This paper attempts to find evidence of the previously proposed opinion that amyloids complex with Congo red molecules which preserve their supramolecular organization....
This paper attempts to find evidence of the previously proposed opinion that amyloids complex with Congo red molecules which preserve their supramolecular organization. As evidence of the overpowering tendency of Congo red molecules to self-assemble, we present an increasing acidity of molecules that follows increasing concentration of the dye, and a highly notable nonlinear increase in absorbance in the UV band (300-400 nm). This effect is analyzed in a model where the amyloid fibril is simulated by polyvinyl alcohol, providing a scaffold to stabilize a long Congo red micelle. Enormous absorbance in the UV band, coupled with the increasing association capabilities of individual Congo red molecules may cause the absorbance to extend even into the visible band. In addition, the UV and visual absorbance bands shift significantly, depending on conditions, and may either approach or recede from each other, leading to spectral changes which may be observed under polarized light. This commonly observed spectral variability appears to be associated with the strong capacity for electron delocalization in supramolecular Congo red complexed with amyloids.
Topics: Amyloid; Bromphenol Blue; Congo Red; Evans Blue; Triazenes
PubMed: 30869081
DOI: 10.18388/abp.2018_2667 -
Dermatology (Basel, Switzerland) 2022Quick and accurate diagnosis of primary cutaneous amyloidosis (PCA) may be difficult because its symptoms are often subtle and nonspecific. (Review)
Review
BACKGROUND
Quick and accurate diagnosis of primary cutaneous amyloidosis (PCA) may be difficult because its symptoms are often subtle and nonspecific.
OBJECTIVE
We sought to review the literature on the roles of various staining methods in the diagnosis of amyloidosis and demonstrate added benefits of using rapid 4,6-diamidino-2-phenylindole (DAPI) staining in the diagnosis of PCA.
METHODS
Three groups of cases, namely, PCA, neurodermatitis, and prurigo nodularis, were retrieved from a computerized pathology database for study, and their paraffin-embedded tissue blocks were cut following standard procedures. The tissue sections were stained with three stains: hematoxylin-eosin (HE), Congo red, and DAPI stains, and examined under the microscope to compare the staining patterns of these three methods. We also performed amyloid keratin and apolipoprotein E (APOE) staining on the sections of PCA in order to further support our conclusion. The PCA sections were read by junior and senior dermatopathologists for comparison.
RESULTS
The sensitivity of DAPI staining for PCA was significantly higher than that of Congo red staining and HE staining (p < 0.001). This statement holds true whether the experiment was grouped in one sample or was divided into groups of junior and senior dermatopathologists (p < 0.001). The DAPI-positive staining areas, except for the nuclei, were consistent with the amyloid deposition areas. In this study, DAPI staining had a sensitivity of 98.6% and a specificity of 100%.
CONCLUSION
DAPI staining could serve as a useful technique to establish the diagnosis of PCA, and its high efficacy in diagnosing PCA makes it less dependent on the experience levels of the evaluators. Additionally, the binding of DAPI to the A-T-rich sequence of double-stranded DNA suggests that amyloid may contain DNA or a similarly structured nucleic acid.
Topics: Amyloidosis; Congo Red; Humans; Indoles; Staining and Labeling
PubMed: 34515096
DOI: 10.1159/000518082 -
Laboratory Investigation; a Journal of... Nov 2023Renal amyloidosis is a rare condition caused by the progressive accumulation of misfolded proteins within glomeruli, vessels, and interstitium, causing functional...
Renal amyloidosis is a rare condition caused by the progressive accumulation of misfolded proteins within glomeruli, vessels, and interstitium, causing functional decline and requiring prompt treatment due to its significant morbidity and mortality. Congo red (CR) stain on renal biopsy samples is the gold standard for diagnosis, but the need for polarized light is limiting the digitization of this nephropathology field. This study explores the feasibility and reliability of CR fluorescence on virtual slides (CRFvs) in evaluating the diagnostic accuracy and proposing an automated digital pipeline for its assessment. Whole-slide images from 154 renal biopsies with CR were scanned through a Texas red fluorescence filter (NanoZoomer S60, Hamamatsu) at the digital Nephropathology Center of the Istituto di Ricovero e Cura a Carattere Scientifico San Gerardo, Monza, Italy, and evaluated double-blinded for the detection and quantification through the amyloid score and a custom ImageJ pipeline was built to automatically detect amyloid-containing regions. Interobserver agreement for CRFvs was optimal (k = 0.90; 95% CI, 0.81-0.98), with even better concordance when consensus-based CRFvs evaluation was compared to the standard CR birefringence (BR) (k = 0.98; 95% CI, 0.93-1). Excellent performance was achieved in the assessment of amyloid score overall by CRFvs (weighted k = 0.70; 95% CI, 0.08-1), especially within the interstitium (weighted k = 0.60; 95% CI, 0.35-0.84), overcoming the misinterpretation of interstitial and capsular collagen BR. The application of an automated digital pathology pipeline (Streamlined Pipeline for Amyloid detection through CR fluorescence Digital Analysis, SPADA) further increased the performance of pathologists, leading to a complete concordance with the standard BR. This study represents an initial step in the validation of CRFvs, demonstrating its general reliability in a digital nephropathology center. The computational method used in this study has the potential to facilitate the integration of spatial omics and artificial intelligence tools for the diagnosis of amyloidosis, streamlining its detection process.
Topics: Humans; Congo Red; Reproducibility of Results; Artificial Intelligence; Amyloid; Staining and Labeling; Amyloidosis
PubMed: 37634845
DOI: 10.1016/j.labinv.2023.100243 -
BioMed Research International 2018Congo red is one of the best known and used azo dyes which has two azo bonds (-N=N-) chromophore in its molecular structure. Its structural stability makes it highly...
Congo red is one of the best known and used azo dyes which has two azo bonds (-N=N-) chromophore in its molecular structure. Its structural stability makes it highly toxic and resistant to biodegradation. The objective of this study was to assess the congo red biodegradation and detoxification by . The effects of pH, initial dye concentration, temperature, and shaking speed on the decolorization rate and enzymes production were studied. The maximum decolorization was correlated with lignin peroxidase and manganese peroxidase production. Above 97% were obtained when 2 g mycelia were incubated at pH 5, in presence of 200 mg/L of dye during 6 days at 28°C and under 120 to 150 rpm shaking speed. The degraded metabolites were characterized by using LC-MS/MS analyses and the biodegradation mechanism was also studied. Congo red bioconversion formed degradation metabolites mainly by peroxidases activities, i.e., the sodium naphthalene sulfonate (m/z = 227) and the cycloheptadienylium (m/z = 91). Phytotoxicity and microtoxicity tests confirmed that degradation metabolites were less toxic than original dye.
Topics: Aspergillus niger; Azo Compounds; Biodegradation, Environmental; Coloring Agents; Congo Red; Water Purification
PubMed: 30175122
DOI: 10.1155/2018/3049686