Prion urine comprises a glycosaminoglycan-light chain IgG complex that can be stained by Congo red

2006 ◽  
Vol 133 (2) ◽  
pp. 205-210 ◽  
Author(s):  
Michele Halimi ◽  
Yael Dayan-Amouyal ◽  
Zehavit Kariv-Inbal ◽  
Yael Friedman-Levi ◽  
Tehila Mayer-Sonnenfeld ◽  
...  
Keyword(s):  
Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 501
Author(s):  
Ptak-Kaczor Magdalena ◽  
Kwiecińska Klaudia ◽  
Korchowiec Jacek ◽  
Chłopaś Katarzyna ◽  
Banach Mateusz ◽  
...  

In the search for new carriers capable of transporting toxic drugs to a target, particular attention has been devoted to supramolecular systems with a ribbon-like micellar structure of which Congo red is an example. A special promise of the possible use of such systems for directing drugs to a target emerges from their particular affinity to immune complexes and as an independent property, binding many organic compounds including drugs by intercalation. Serum albumin also appeared able to bind micellar particles of such systems. It may protect them against dilution in transport. The mathematical tool, which relies on analysis of the distribution of polarity and hydrophobicity in protein molecules (fuzzy oil drop model), has been used to find the location of binding area in albumin as well as anchorage site for Congo red in heated IgG light chain used as a model presenting immunoglobulin-like structures. Results confirm the suggested formerly binding site of Congo red in V domain of IgG light chain and indicated the cleft between pseudo-symmetric domains of albumin as the area of attachment for the dye.


2019 ◽  
Vol 5 (5) ◽  
pp. e326-e329 ◽  
Author(s):  
John J. Orrego ◽  
Joseph A. Chorny

Objective: Clinically apparent thyroid enlargement due to massive amounts of amyloid deposition, known as amyloid goiter, is rare. Endocrinologists should become familiar with this manifestation of systemic amyloidosis, which may be diagnosed by Congo red staining of the specimen obtained by fine-needle aspiration. Methods: We describe a 70-year-old man who presented with a slowly enlarging goiter. It was asymptomatic, predominantly left-sided, nontoxic, and multinodular with atypia of undetermined significance (Bethesda System category III) by cytology. The goiter tested negative using the ThyraMIR miRNA Gene Expression Classifier kit (eviCore Healthcare, Bluffton, SC). Results: Left thyroid lobectomy produced a 220-g specimen with nodular hyperplasia and prominent amyloid deposition confirmed by Congo red staining. Liquid chromatography tandem mass spectrometry detected a peptide profile consistent with light chain amyloid deposition of the lambda type, formerly called primary amyloidosis. In retrospect, he had been diagnosed with restrictive cardiomyopathy, cardiac conduction system disease, coronary artery disease, non-nephrotic range proteinuria, and chronic kidney disease, which had been attributed to his longstanding type 2 diabetes mellitus. Extensive workup subsequently demonstrated cardiac amyloidosis and monoclonal gammopathy of unknown significance, consistent with light chain amyloidosis. Conclusion: Amyloid goiter should be included in the differential diagnosis of enlarging goiters with Bethesda System category III cytology in patients with monoclonal gammopathy of uncertain significance, clinical manifestations of systemic amyloidosis, or known diagnosis of monoclonal cell dyscrasia.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5601-5601
Author(s):  
Andrew J. Cowan ◽  
David G. Coffey ◽  
Teresa S. Hyun ◽  
Pamela S. Becker ◽  
Damian J. Green ◽  
...  

Abstract Background: The amyloidoses comprise a heterogeneous group of diseases characterized by misfolding of amyloidogenic proteins and subsequent deposition as amyloid fibrils. To date, over 30 proteins are known to be amyloidogenic (Sipe Amyloid 2014). Immunoglobulin light chain (AL) amyloidosis, a plasma cell dyscrasia, is the most common subtype. The standard diagnostic algorithm in AL amyloidosis is to obtain a biopsy of a clinically involve organ, and once Congo red positivity is confirmed, perform subtyping analyses with immunohistochemistry or mass spectrometry. Accurate subtyping of amyloidosis is essential to appropriate treatment, as misdiagnosis occurs in up to 10% of patients and may lead to inappropriate administration of chemotherapy (Comenzo Blood 2006; Lachmann NEJM 2002). We sought to determine the patterns of amyloid subtyping among patients with a diagnosis of AL amyloidosis referred to a tertiary referral center for HDM/SCT. Methods: Sequential patients with confirmed amyloidosis, age ≥ 18 years who underwent HDM/SCT between 2001 and 2014 at the Fred Hutchinson Cancer Research Center and University of Washington Medical Center were eligible. Presence of a Congo red-positive biopsy for each patient referred for transplant was confirmed and the pathology reports and medical records were reviewed to determine if subtyping was performed, and which modality was used. Results: Fifty-one patients with AL amyloidosis were referred for transplant; of these, 45 proceeded with HDM/SCT. The organ systems most commonly involved were renal in 34/51, and gastrointestinal in 5/51. Of the biopsies, subtyping was performed in 35 (68.6%), and no subtyping was performed in 16 patients (31.3%). Immunofluorescence was the most common modality used for subtyping in 33 biopsies (94.2%) and laser capture/mass spectrometry (LC/MS) was used in 2 patients (5.7%). All patients had evidence of a clonal plasma cell dyscrasia by bone marrow biopsy and peripheral blood testing. Of the patients without subtyping, 8 (50%) were diagnosed before 2008. Discussion: Misdiagnosis of amyloidosis due to a lack of appropriate subtyping is a well-described and ongoing problem for patients with amyloidosis. These data suggest that definitive subtyping is still not routinely performed in the evaluation of amyloidosis. At our center, efforts to standardize the evaluation of Congo-red positive biopsies using definitive typing are underway. Disclosures Gopal: Seattle Genetics: Research Funding.


2020 ◽  
Vol 57 (5) ◽  
pp. 658-665
Author(s):  
Ayumi Kadota ◽  
Susumu Iwaide ◽  
Shinya Miyazaki ◽  
Ikki Mitsui ◽  
Noboru Machida ◽  
...  

Amyloidosis is classified according to the amyloid precursor protein, and accurate diagnosis of the amyloidosis type may guide appropriate treatment. Immunohistochemistry and Congo red staining are the most frequently used methods used to distinguish types of amyloidosis, but problems with specificity and sensitivity indicate the need for an alternative diagnostic method. In this study, we evaluated laser microdissection-liquid chromatography-tandem mass spectrometry (LMD-LC-MS/MS) for the diagnosis of amyloid light-chain (AL) amyloidosis in animals. Plasmacytomas with amyloid deposits from 15 dogs and 2 cats were subjected to Congo red staining with or without potassium permanganate pretreatment, immunohistochemistry for kappa and lambda light chains, and LMD-LC-MS/MS. Congo red staining was diagnostic in 12 of 17 cases based on resistance to potassium permanganate pretreatment, but in 5 of 17 cases the pretreatment unexpectedly reduced Congo red staining or abrogated the birefringence and a definitive diagnosis could not be reached. Immunohistochemistry detected kappa or lambda light chains in 6 of 17 cases. With LMD-LC-MS/MS, immunoglobulin lambda light chain was detected in all 17 cases. The amyloid signature proteins ApoA-I, ApoA-IV, and ApoE were detected in 9, 1, and 3 of the 15 canine cases by LMD-LC-MS/MS, but not in the feline cases. In conclusion, LMD-LC-MS/MS consistently determined the amyloid type in all examined specimens, while Congo red staining after potassium permanganate treatment and immunohistochemistry were less sensitive tests.


2018 ◽  
Vol 12 (2) ◽  
pp. 317-321 ◽  
Author(s):  
Matthew Hoscheit ◽  
Afrin Kamal ◽  
Michael Cline

Systemic amyloidosis is a group of complex disorders characterized by the extracellular deposition of nonbranching fibrils in various tissues, ultimately leading to a variety of clinical presentations including isolated or multiorgan dysfunction. Amyloid involvement of the gastrointestinal tract is common depending on the subtype of this disease; light chain primary amyloidosis (AL) and secondary amyloidosis (AA) affect the gastrointestinal tract in unique ways due to differing pathophysiology. A case is reported of gastroparesis associated with AL amyloidosis diagnosed by esophagogastroduodenoscopy and study of gastric emptying, then subsequently confirmed by Congo red staining performed on endoscopic biopsies.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Li-Jun Sun ◽  
Hong-Rui Dong ◽  
Xiao-Yi Xu ◽  
Guo-Qin Wang ◽  
Hong Cheng ◽  
...  

Abstract Background Light chain cast nephropathy (LCCN) is the most common renal disease caused by multiple myeloma (MM). In addition to ordinary light chain protein casts, there are a few rare casts with unique shapes, including light chain amyloid casts (LCAC) and light chain crystal casts (LCCC). Case presentations Here, we report two patients. Patient 1 is a 72-year-old man who was clinically diagnosed with MM and acute kidney injury (AKI). Pathological examination of a renal biopsy revealed that there were many amyloid casts in the distal tubules that had a lightly-stained central area and a deeply-stained burr-like edge. The marginal zone of the cast was positive for Congo red staining and contained numerous amyloid fibers, as observed by electron microscopy. No systemic amyloidosis was found. The patient received 4 courses of bortezomib-based chemotherapy, and then, his MM achieved partial remission. Patient 2 is a 57-year-old man who was also clinically diagnosed with MM and AKI. Pathological examination of a renal biopsy showed that there were many crystalline casts in the distal tubules that were fully or partially composed of crystals with different shapes, including rhomboid, needle, triangle, rectangle and other geometric shapes. Congo red staining was negative. Crystals were also detected in the urine of this patient. After 9 courses of treatment with a bortezomib-based regimen, his MM obtained complete remission and his renal function returned to normal. Conclusions LCAC and LCCC nephropathy caused by MM are two rare types of LCCN, and both have their own unique morphological manifestations. LCAC nephropathy may not be accompanied by systemic amyloidosis. The diagnosis of these two unique LCCNs must rely on renal biopsy pathology, and the discovery of urine crystals is of great significance for indicating LCCC nephropathy.


2020 ◽  
Vol 07 (04) ◽  
pp. 15-19
Author(s):  
Sanjay Kumar ◽  

Fifty-eight-year-old male admitted for evaluation of nephrotic syndrome and chronic diarrhoea was detected to have Immunoglobulin light chain amyloidosis (AL Amyloidosis) which was congo red inconclusive from renal biopsy. Bone marrow biopsy showed monoclonal plasma cells of 40% and light chain assay showed predominance of immunoglobulin lambda light chain. The diagnosis was neither fitting into the current diagnostic criteria for light chain Monoclonal Gammopathy of Renal Significance (MGRS) nor light chain myeloma. Literature is scarce regarding patients with AL amyloidosis having underlying clonal expansion not meeting the criteria of light chain myeloma or light chain MGRS.


2006 ◽  
Vol 15 (7) ◽  
pp. 1710-1722 ◽  
Author(s):  
Richard W. Mclaughlin ◽  
Janelle K. De Stigter ◽  
Laura A. Sikkink ◽  
Elizabeth M. Baden ◽  
Marina Ramirez-Alvarado

2021 ◽  
Vol 14 (4) ◽  
pp. e241282
Author(s):  
Karen Tsai ◽  
Alice Chen Yu ◽  
Masha J Livhits ◽  
Dipti Sajed ◽  
Angela M Leung ◽  
...  

A 74-year-old woman with a history of primary hyperparathyroidism, thyroid nodules, atrial fibrillation and pacemaker placement for sick sinus syndrome presented with fatigue, constipation and persistent lower extremity oedema. She underwent subtotal parathyroidectomy and left thyroid lobectomy. Histopathology revealed amyloidosis affecting the thyroidand parathyroids confirmed by Congo Red Staining with Mayo Clinic subtyping of light chain kappa-type amyloidosis. She was found to have combined systolic and diastolic cardiac dysfunction, carpal tunnel neuropathy and pre-diabetes suggestive of systemic amyloidosis with involvement of the heart, nerves and pancreas. Congo red stain was positive for amyloidosis on bone marrow biopsy suggestive of a diagnosis of systemic amyloidosis. She was treated with daratumumab with good clinical response. This case illustrates the necessity of considering systemic amyloidosis in patients with incidentally discovered diffuse amyloid deposits on biopsy of an endocrine organ, as endocrine effects are a rare but likely underdiagnosed consequence of systemic amyloidosis.


Sign in / Sign up

Export Citation Format

Share Document