Electron and immuno-electron microscopy of abdominal fat identifies and characterizes amyloid fibrils in suspected cardiac amyloidosis

Abstract

We evaluated the role of electron microscopy and immuno-electron microscopy studies on abdominal fat fine-needle biopsy samples in diagnosis and characterization of cardiac amyloidosis. The series consists of 15 patients with echocardiographic evidence of "restrictive cardiomyopathy" suspected to be due to amyloidosis. Patients underwent: clinical examination, electrocardiography, 2-D and Doppler echocardiography, immunofixation of serum and urine for detection of monoclonal immunoglobulins, and abdominalfat biopsies that were investigated with polarized light (Congo red), electron and immuno-electron microscopy using specific antibodies to kappa and lambda light chains, apolipoprotein A1, serum amyloid A (SAA), and transthyretin (TTR). Ultrastructural study of abdominal fat samples identified amyloid deposits in 15/15 cases. Immuno-electron microscopy specifically stained amyloid fibrils with antibodies anti-lambda (n = 8), -kappa (n = 2), -apolipoprotein A1 (n = 2) and -TTR (n = 3). Immuno-electron microscopy revealed TTR immuno-labelling in 2 patients with accidental monoclonal components, and a A reaction in I patient without monoclonal components. TTR and apolipoprotein A1 positive cases carried missense mutations in the corresponding genes. Our results demonstrate that amyloid deposits are present in the abdominalfat of patients suspected to have cardiac amyloidosis and that immuno-electron microscopy was able to characterize the amyloid protein in all cases.

Melphalan and dexamethasone with or without bortezomib in newly diagnosed AL amyloidosis: a matched case–control study on 174 patients

“…The amyloid deposits were characterized as AL-type by immunoelectron microscopy or proteomics in all cases. 34,35 Evidence of a monoclonal component of the same isotype of that identified in the amyloid fibrils at serum and urine immunofixation electrophoresis and/or an abnormal FLC κ/λ ratio was required. 36 Subjects with lytic bone lesions were excluded.…”

Best use of cardiac biomarkers in patients with AL amyloidosis and renal failure

“…The diagnosis of amyloidosis was biopsy proven and the amyloid deposits were characterized as AL type by immunoelectron microscopy [17]. Hereditary forms were excluded by DNA analysis.…”

Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): A consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis

“…Hepatic amyloidosis occurs in apolipoprotein A-I, lysozyme, immunoglobulin light chain, and AA types [40,41]. Cardiac amyloidosis and amyloid neuropathy are associated with scores of mutations of transthyretin [42], and immunohistochemical staining with commercially available anti-transthyretin antisera [39] is specific [43]. When definitive immunohistochemical typing of amyloid cannot be achieved, specific genetic studies can be performed by polymerase chain reaction to recognize mutations in transthyretin [44,45], fibrinogen, lysozyme [46], and apolipoproteins A-I and A-II.…”