Prevalence and morphology of leukocyte chemotactic factor 2-associated amyloid in renal biopsies

Abstract

Renal pathologists identify the protein component of renal amyloid deposits by immunohistochemistry using antibodies against known amyloidogenic proteins. The majority of amyloid cases can be categorized by a simple antibody panel that includes immunoglobulin light chains lambda and kappa, and serum amyloid A. In some instances, however, these reagents do not recognize materials that stain with Congo red or yield ambiguous staining results, thus creating a diagnostic dilemma. Chemical analysis of fibrils extracted from such a nonreactive renal biopsy led to the discovery of a previously unknown amyloid formed from leukocyte chemotactic factor 2 (LECT2). Over the past 8 years, we received 285 renal amyloid samples, of which 31 remained unclassified. In an effort to determine whether any of the latter samples were LECT2 related, tandem mass spectrometry was performed. In all, 7 of the 31 cases were identified as an amyloid LECT2 (ALECT2), a finding confirmed immunohistochemically using a LECT2-specific antibody. The deposits strongly stained for Congo red and, in most cases, had distinctive morphological features with diffuse involvement of the interstitium, arteries, and glomeruli. Hence, we believe that ALECT2 represents the third common form of renal amyloidosis.

Figure 1 |. LECT2-associated renal amyloidosis (light microscopy).

(a) Extensive mesangial replacement by periodic acid-Schiff and (b) Jones methenamine silver-negative amorphous material (× 400). (c) Reactivity of glomerular and interstitial amyloid deposits with an anti-LECT2 antibody (immunoperoxidase technique, × 100). (d) Uptake of Congo red stain by interstitial and glomerular amyloid deposits (× 100). LECT2, leukocyte chemotactic factor 2.