High-sensitivity diagnosis of AA amyloidosis using Congo red and                immunohistochemistry detects missed amyloid deposits.

Linke, Reinhold P.; Hv, Gärtner; Michels, H.

doi:10.1177/43.9.7642960

Cited by 62 publications

(45 citation statements)

References 4 publications

(4 reference statements)

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“…Immunohistochemistry is usually definitive in identifying or ruling out AA amyloidosis, but it frequently is not diagnostic with respect to AL amyloidosis. 8,21 In our series, AL fibrils were identified by immunohistochemical staining in only 121 of the 316 patients with confirmed AL disease (38 percent). This reflects the failure of anti-light-chain antibodies to bind to light-chain fragments with an abnormal cross-b amyloid-fibril conformation and also reflects background staining of normal immunoglobulins in the tissues.…”

Section: Discussionmentioning

confidence: 60%

Misdiagnosis of Hereditary Amyloidosis as AL (Primary) Amyloidosis

et al. 2002

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Section: Discussionmentioning

confidence: 60%

Misdiagnosis of Hereditary Amyloidosis as AL (Primary) Amyloidosis

et al. 2002

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“…8 In a study, immunohistochemical analysis was reported as a helpful method to evaluate the overlooked or trace deposits of amyloidosis. 16 In this study, Congo Red method (Liebs and Bennhold's methods) for amyloid A staining was used for the evaluation of amount, localization, and type of glomerular accumulation.…”

Section: Discussionmentioning

confidence: 99%

Phenotype 2 Familial Mediterranean Fever: Evaluation of 22 Case Series and Review of the Literature on Phenotype 2 FMF

Altunoğlu¹,

Erten

Canöz

et al. 2012

Renal Failure

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Familial Mediterranean fever (FMF) is an autosomal recessive autoimmune disorder characterized by recurrent bouts of fever and serosal inflammation. FMF may be complicated by AA-type amyloidosis, worsening the prognosis, with associated renal failure in some patients. Complication rate varies with race, being as high as 60% in Turks and as low as 2% in Armenians. In a few cases of patients with FMF (phenotype 2), amyloid nephropathy may be the presenting manifestation. This study included 420 patients who were admitted to the Nephrology and Rheumatology Departments of Atatürk Education and Research Hospital with unexplained proteinuria/nephrotic syndrome. The initial screening test for amyloidosis was the presence of significant proteinuria (300 mg/24 h). All MEFV gene exons were screened for causative mutations by direct DNA sequencing to check for any mutations. There were 22 phenotype 2 FMF patients with 27 allelic variants. The most prevalent allelic variants were M694V (10/27, 37%) and E148Q (7/27, 26%). Phenotype 2 FMF is not as rare as it was thought before; this should be kept in mind for all patients with unexplained proteinuria and/or acute phase response in high-risk ethnic groups for FMF.

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“…Despite the durability of this assay, the optical characterization of amyloid has not progressed and is ambiguous (8,9). The birefringence is rarely quantified, a problem further confounded by the fact that CR does not stain amyloid consistently, and diagnosis by staining depends on the skill of the investigator.…”

mentioning

confidence: 99%

Imaging linear birefringence and dichroism in cerebral amyloid pathologies

Jin

Claborn

Kurimoto

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

187

149

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New advances in polarized light microscopy were used to image Congo red-stained cerebral amyloidosis in sharp relief. The rotating-polarizer method was used to separate the optical effects of transmission, linear birefringence, extinction, linear dichroism, and orientation of the electric dipole transition moments and to display them as false-color maps. These effects are typically convolved in an ordinary polarized light microscope. In this way, we show that the amyloid deposits in Alzheimer's disease plaques contain structurally disordered centers, providing clues to mechanisms of crystallization of amyloid in vivo. Comparisons are made with plaques from tissues of subjects having Down's syndrome and a prion disease. In plaques characteristic of each disease, the Congo red molecules are oriented radially. The optical orientation in amyloid deposited in blood vessels from subjects having cerebral amyloid angiopathy was 90°out of phase from that in the plaques, suggesting that the fibrils run tangentially with respect to the circumference of the blood vessels. Our result supports an early model in which Congo red molecules are aligned along the long fiber axis and is in contrast to the most recent binding models that are based on computation. This investigation illustrates that the latest methods for the optical analysis of heterogeneous substances are useful for in situ study of amyloid.T he abnormal transformation of proteins to amyloid fibrils is closely related to the so-called conformational diseases that include the common neurodegenerative disorders such as Alzheimer's disease (AD) and prion diseases. The kinetic and structural bases of fibrillogenesis in these diseases are as yet undetermined. Nevertheless, the presence of amyloid in diseased tissues has been used for the purpose of pathological diagnosis and construction of theories of pathogenesis. A structural characterization and categorization of various forms of amyloid aid accurate diagnosis of amyloid disorders and further our mechanistic understanding of an increasing list of conformational diseases.The principal diagnostic criterion of amyloidosis, established by Divry and Florkin (1), is the detection with a polarizing optical microscope of so-called apple-green birefringence (2-6) from Congo red (CR)-stained tissue sections (7). Despite the durability of this assay, the optical characterization of amyloid has not progressed and is ambiguous (8, 9). The birefringence is rarely quantified, a problem further confounded by the fact that CR does not stain amyloid consistently, and diagnosis by staining depends on the skill of the investigator. Clearly, new opticalcontrast mechanisms are required for simple, reliable amyloid diagnosis (10, 11).Here, we show that recent advances in polarized light microscopy can be used to quickly quantify and refine our description of CR-stained amyloid. In particular, we applied a newly developed imaging system to separate the optical transmission, refractive index anisotropy [linear birefringence (LB)], and optic...

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High-sensitivity diagnosis of AA amyloidosis using Congo red and immunohistochemistry detects missed amyloid deposits.

Cited by 62 publications

References 4 publications

Misdiagnosis of Hereditary Amyloidosis as AL (Primary) Amyloidosis

Misdiagnosis of Hereditary Amyloidosis as AL (Primary) Amyloidosis

Phenotype 2 Familial Mediterranean Fever: Evaluation of 22 Case Series and Review of the Literature on Phenotype 2 FMF

Imaging linear birefringence and dichroism in cerebral amyloid pathologies

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