Distribution of amyloidosis subtypes based on tissue biopsy site − Consecutive analysis of 729 patients at a single amyloidosis center in Japan

Abstract

This study was performed to elucidate the distribution of amyloidosis subtypes based on tissue biopsy site. Samples obtained from 729 consecutive patients with amyloidosis were analyzed by immunohistochemical staining (IHC) and supplemental mass spectrometry (MS). The correlations between the type of organs from which samples were obtained and amyloidosis subtypes were investigated retrospectively. Among the patients, 95.1% were diagnosed by IHC and 4.9% were diagnosed by MS. The distribution of amyloidosis subtypes was as follows: AL, 59.1%; ATTR, 32.9%; AA, 4.0%; AH, 1.4%; Aβ2M, 0.8%; and others, 0.9%. AL was the most common subtype in most organs, including the liver, lung, kidney, lower urinary tract, bone marrow, gastrointestinal tract, and skin/subcutaneous tissue. ATTR was the most common subtype in the heart, carpal tunnel, and peripheral nerves. AH was the second most common subtype in renal biopsy. Three or more amyloidosis subtypes were detected in each organ. In conclusion, AL was the most common subtype in most biopsy sites except the heart, carpal tunnel, and peripheral nerve, in which ATTR was more common. Because several types of amyloidogenic protein were detected in each organ, amyloid typing must be pursued, no matter the site from where biopsy was obtained.

Development of diagnostic antibodies against immunoglobulin heavy chain variable region for heavy chain amyloidosis (AH amyloidosis)

“…Immunohistochemistry analysis using AH1 and AH2 antibodies was performed on tissue samples obtained by biopsy or autopsy of 11 patients with AH amyloidosis, including 1 unreported patient 8–10,14,18 . The diagnosis of AH amyloidosis was confirmed by amino acid sequence analysis or LMD/MS analysis performed at Shinshu University, Japan 18 . IHC studies using anti‐λlight chain, anti‐κlight chain, anti‐amyloid A (AA), and anti‐transthyretin (TTR) antisera 18 revealed that 11 patients were negative for these proteins.…”

“…The diagnosis of AH amyloidosis was confirmed by amino acid sequence analysis or LMD/MS analysis performed at Shinshu University, Japan 18 . IHC studies using anti‐λlight chain, anti‐κlight chain, anti‐amyloid A (AA), and anti‐transthyretin (TTR) antisera 18 revealed that 11 patients were negative for these proteins. The clinical information and biochemical data for the amyloid fibril proteins in these patients are presented in Table 1.…”

“…In addition, IHC analysis using AH1 and/or AH2 antibodies was performed on tissue samples from 64 non‐AH amyloidosis patients (44 with AL amyloidosis, 7 with AA amyloidosis, 9 with TTR‐related amyloidosis, 3 with β 2 ‐microglobulin amyloidosis, and 1 with gelsolin‐related amyloidosis), for whom diagnosis was confirmed by IHC studies 18 or in DNA analysis (for gelsolin‐related amyloidosis).…”

“…To date, no more than 50 patients with heavy chain related amyloidosis, including those with heavy chain/light chain amyloidosis (AHL amyloidosis), have been reported 3–18 . In AH amyloidosis, the kidney is the most severely affected organ, 3–18 and most patients have underlying monoclonal gammopathy associated with B‐lymphocyte or plasma cell proliferation, similar to AL amyloidosis. We previously reported several differences in histopathological findings between AL and AH amyloidosis 19 .…”

“…Thus, deposited amyloid proteins derived from Ig heavy chains often go undetected in immunohistochemistry (IHC) analysis using commercially available antibodies 8–10,14 . Detailed biochemical investigation of the deposited amyloid protein is required for accurate diagnosis of AH amyloidosis 3,4,8–10,14,18 . Recently, proteomic analysis using laser microdissection‐liquid chromatography‐tandem mass spectrometry (LMD/MS) has become the gold standard for diagnosing AH amyloidosis 11,12 .…”