How I treat amyloidosis: the importance of accurate diagnosis and amyloid typing

Leung, Nelson; Nasr, Samih H.; Sethi, Sanjeev

doi:10.1182/blood-2012-03-413682

Cited by 132 publications

(102 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Precise amyloid typing is crucial for the adequate treatment of patients because the various forms require different approaches, which can range from autologous stem cell transplantation in amyloid light-chain (AL) amyloidosis to liver transplantation in transthyretin (TTR) amyloidosis (ATTR). 2,4,5 Diagnosis and classification are based on histologic demonstration of amyloid deposits and characterization of the amyloid precursor. Abdominal subcutaneous fat aspiration with a fine needle is fast and harmless and is the most common diagnostic tool when a systemic form is suspected, 6 offering a convenient alternative to organ biopsy.…”

mentioning

confidence: 99%

A practical approach to the diagnosis of systemic amyloidoses

Larrea

Verga

Morbini

et al. 2015

Blood

172

106

View full text Add to dashboard Cite

Key Points• The first wide, prospective report on the role of IEM in the differential diagnosis of systemic amyloidosis.• IEM allows for the correct characterization of the amyloid protein in virtually all cases and represents a viable alternative to mass spectrometry.Accurate diagnosis of systemic amyloidosis is necessary both for assessing the prognosis and for delineating the appropriate treatment. It is based on histologic evidence of amyloid deposits and characterization of the amyloidogenic protein. We prospectively evaluated the diagnostic performance of immunoelectron microscopy (IEM) of abdominal fat aspirates from 745 consecutive patients with suspected systemic amyloidoses. All cases were extensively investigated with clinical and laboratory data, with a follow-up of at least 18 months. The 423 (56.8%) cases with confirmed systemic forms were used to estimate the diagnostic performance of IEM. Compared with Congo-red-based light microscopy, IEM was equally sensitive (75% to 80%) but significantly more specific (100% vs 80%; P < .001). In amyloid light-chain (AL) amyloidosis, k cases were more difficult to diagnose (sensitivity 71%), whereas the analysis of abdominal aspirate was informative in only 40% of patients with transthyretin amyloidosis. We found a high prevalence (20%) of a monoclonal component in patients with non-AL amyloidosis, highlighting the risk of misdiagnosis and the need for unequivocal amyloid typing. Notably, IEM identified correctly the specific form of amyloidosis in >99% of the cases. IEM of abdominal fat aspirates is an effective tool in the routine diagnosis of systemic amyloidoses. (Blood. 2015;125(14):2239-2244) IntroductionAmyloidosis is a heterogeneous group of diseases that share the deposition of amyloid fibrils in organs and tissues, with the same characteristic cross-b-sheet secondary structure, independently of their protein primary structure.1 More than 30 unrelated autologous proteins can produce systemic amyloidoses, 2-5 either localized or systemic. The various forms differ in pathogenesis and prognosis, but they usually show overlapping clinical manifestations, making their differentiation on clinical grounds very difficult. Precise amyloid typing is crucial for the adequate treatment of patients because the various forms require different approaches, which can range from autologous stem cell transplantation in amyloid light-chain (AL) amyloidosis to liver transplantation in transthyretin (TTR) amyloidosis (ATTR). 2,4,5 Diagnosis and classification are based on histologic demonstration of amyloid deposits and characterization of the amyloid precursor. Abdominal subcutaneous fat aspiration with a fine needle is fast and harmless and is the most common diagnostic tool when a systemic form is suspected, 6 offering a convenient alternative to organ biopsy. The resulting tissue smear is examined by polarized light microscopy (LM) after Congo red staining in order to detect the presence of amyloid. The second step is to identify the amyloidogenic protein in order to u...

show abstract

mentioning

confidence: 99%

A practical approach to the diagnosis of systemic amyloidoses

Larrea

Verga

Morbini

et al. 2015

Blood

172

106

View full text Add to dashboard Cite

show abstract

“…Amyloid precursors often have genetic mutations and undergo conformational changes. Antibodies produced against the wild-type protein may be less reactive against the mutant form, which seems particularly problematic for AL (19,20). Therefore, the type of amyloidosis (AA or AL) could not be determined in the present case, but our review demonstrated that TBA with Sjögren's syndrome could be present as not only the AA type (n=3) but also the AL type (n=6), and only one-third of the patients had an antecedent diagnosis of Sjögren's syndrome.…”

Section: Discussionmentioning

confidence: 99%

Tracheobronchial Amyloidosis in a Patient with Sjögren's Syndrome

et al. 2016

View full text Add to dashboard Cite

A 65-year-old woman was referred to our respiratory department because of incidentally detected endobronchial deposits. She had been diagnosed with Sjögren's syndrome 12 years earlier. Bronchoscopy showed protrusion of the reddened, shiny or edematous mucosa at the orifice of the lower lobe bronchus, suggesting a submucosal tumor. Based on the pathological findings of the transbronchial biopsied specimens, the patient was diagnosed with non-classified type tracheobronchial amyloidosis associated with Sjögren's syndrome, which was negative for both λ and κ chains, transthyretin and amyloid A. She has remained in good health without a relapse of the tumor.

show abstract

“…; C3G, C3 glomerulopathy; MIDD, monoclonal Ig deposition disease; PGNMID, proliferative GN with monoclonal Ig deposits; POEMS, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes. (38). However, mass spectrometry with proteomic analysis has become the gold standard for amyloid typing (39).…”

Section: Glomerular Lesions Aig Amyloidosismentioning

confidence: 99%

Dysproteinemias and Glomerular Disease

Leung

Drosou

Nasr

2017

CJASN

Self Cite

View full text Add to dashboard Cite

Dysproteinemia is characterized by the overproduction of an Ig by clonal expansion of cells from the B cell lineage. The resultant monoclonal protein can be composed of the entire Ig or its components. Monoclonal proteins are increasingly recognized as a contributor to kidney disease. They can cause injury in all areas of the kidney, including the glomerular, tubular, and vascular compartments. In the glomerulus, the major mechanism of injury is deposition. Examples of this include Ig amyloidosis, monoclonal Ig deposition disease, immunotactoid glomerulopathy, and cryoglobulinemic GN specifically from types 1 and 2 cryoglobulins. Mechanisms that do not involve Ig deposition include the activation of the complement system, which causes complement deposition in C3 glomerulopathy, and cytokines/growth factors as seen in thrombotic microangiopathy and precipitation, which is involved with cryoglobulinemia. It is important to recognize that nephrotoxic monoclonal proteins can be produced by clones from any of the B cell lineages and that a malignant state is not required for the development of kidney disease. The nephrotoxic clones that do not meet requirement for a malignant condition are now called monoclonal gammopathy of renal significance. Whether it is a malignancy or monoclonal gammopathy of renal significance, preservation of renal function requires substantial reduction of the monoclonal protein. With better understanding of the pathogenesis, clone-directed strategies, such as rituximab against CD20 expressing B cell and bortezomib against plasma cell clones, have been used in the treatment of these diseases. These clone-directed therapies been found to be more effective than immunosuppressive regimens used in nonmonoclonal protein-related kidney diseases.

show abstract

How I treat amyloidosis: the importance of accurate diagnosis and amyloid typing

Cited by 132 publications

References 72 publications

A practical approach to the diagnosis of systemic amyloidoses

A practical approach to the diagnosis of systemic amyloidoses

Tracheobronchial Amyloidosis in a Patient with Sjögren's Syndrome

Dysproteinemias and Glomerular Disease

Contact Info

Product

Resources

About

How I treat amyloidosis: the importance of accurate diagnosis and amyloid typing

Cited by 132 publications

References 72 publications

A practical approach to the diagnosis of systemic amyloidoses

A practical approach to the diagnosis of systemic amyloidoses

Tracheobronchial Amyloidosis in a Patient with Sj&ouml;gren's Syndrome

Dysproteinemias and Glomerular Disease

Contact Info

Product

Resources

About

Tracheobronchial Amyloidosis in a Patient with Sjögren's Syndrome