Leukocyte Chemotactic Factor 2: A Novel Cause of Renal and Hepatic Amyloidosis Associated with Nephrotic Syndrome and Chronic Liver Disease
A Dogan, VJ Zepeda, JA Vrana, JD Theis, JD Gamez, R Valdez, JW Williams, R Fonseca. Mayo Clinic, Rochester
Background: In this study, we describe a novel-type of amyloidosis caused by deposition of a chemokine, leukocyte chemotactic factor 2 (LECT2) which may account for the majority of unclassifiable amyloidosis seen in renal and liver biopsies.
Design: Eight cases of renal or hepatic amyloidosis, where amyloid type can not be determined after extensive pathological and clinical investigations, were studied. The amyloid typing was performed by immunohistochemistry for common types of amyloid (ATTR, SAA, AL) as well as LECT2 and by nano-flow liquid chromatography electrospray tandem mass spectrometry (MS/MS) following laser microdissection and proteolytic digestion of the amyloid deposits. The resulting MS/MS data was correlated to theoretical fragmentation patterns of tryptic peptide sequences from the Swissprot database using Scaffold algorithm. The identified proteins were examined for the presence or absence of amyloid related peptides. 90 cases of AL, ATTR and SAA amyloidosis and normal glomeruli from 10 different cases were studied as controls.
Results: Six of the patients were male, two female, the median age was 66 (range 41-76). Five cases presented with nephrotic syndrome. Two cases presented with chronic liver disease secondary to viral hepatitis and one case was an incidental finding in a liver biopsy performed during a cholecystectomy. In all cases, the amyloidosis appered to be localized to the kidney or the liver. None of the patient had family history or clinical findings supporting AL, SAA or ATTR amyloidosis. In each case, MS/MS analysis showed that one of the most abundant peptides was LECT2. No other amyloid associated peptides were present. In contrast, in the control cases involved by AL, SAA or ATTR and in normal renal tissue no LECT2 peptides were present. Immunohistochemical studies for AL, ATTR and SAA was negative whereast, in each case the amyloid deposits were strongly positive for LECT2 confirming MS/MS findings.
Conclusions: In this study, we described a novel-type of amyloidosis caused by deposition of LECT2. LECT2 amyloidosis typically presents with isolated renal involvement and nephrotic syndrome or liver involvement and chronic hepatitis. The clinical and pathological features of LECT2 amyloidosis closely mimic AL amyloidosis and should be considered in the differential diagnosis. The underlying cause for LECT2 amyloidosis remains unknown but an association with chronic inflammation is suggested in cases with liver involvement.
Category: Kidney (does not include tumors)
Monday, March 9, 2009 8:00 AM
Platform Session: Section G 1, Monday Morning