LECT2 – A New Cause of Hepatic Amyloidosis

Editorial

Austin Liver. 2016; 1(1): 1001.

LECT2 – A New Cause of Hepatic Amyloidosis

Richards RJ¹* and Nadir A²

¹Department of Gastroenterology, Mountain View Regional Medical Center, New Mexico

²Department of Gastroenterology, Maricopa Medical Center, Arizona

*Corresponding author: Robert J. Richards, Department of Gastroenterology, Mountain View Regional Medical Center, Las Cruces, New Mexico

Received: June 23, 2016; Accepted: June 24, 2016; Published: July 05, 2016

Editorial

Amyloidosis is caused by an abnormal deposition and accumulation of insoluble protein fibrils in multiple organs, often leading to diverse clinical presentations, and possible organ failure. On Congo-Red staining, amyloid fibrils form characteristic betapleated sheets that typically show apple, green birefringence upon polarization under light microscopy. The kidney is the most common organ affected in systemic amyloidosis. The liver is involved less frequently than the kidney. In this editorial we present a recently discovered amyloid protein - LECT2 (leukocyte chemotactic factor 2) that has been documented to affect the kidney and the liver.

Of more than 30 types of amyloid protein fibrils discovered thus far, LECT2 is one of the most recently described. It was initially reported to present with slowly progressive renal failure and nephrotic syndrome [1,2].

In the United States, LECT2 protein has been found to be especially prevalent among people of Hispanic ethnicity [1]. In an autopsy series, LECT2 amyloid deposits were identified within the kidney in 3.1% of Hispanics, and could represent an important but under-recognized etiology of chronic kidney disease in this population [1,3]. Two large case series focusing on renal amyloidosis identified LECT2 as the second and third most common form of renal amyloidosis respectively [3,4]. LECT2 fibrils are found in the glomeruli, renal vessels, and interstitium. Other organs including the liver, spleen, adrenals, and lungs but not myocardium or brain have been reported to be involved with LECT-2 amyloid protein [1,5].

A recent large case series identified LECT2 as the second most common form of hepatic amyloidosis [6]. In this series LECT2 accounted for up to 25% of hepatic amyloid cases. LECT2 is synthesized mainly by the liver and is considered to be a hepatokine. The exact biological function of LECT2 is not precisely known. In the liver, it acts as is an eutrophilic chemotactic factor. It also plays a role in hepatocyte regeneration [6]. Increased expression of LECT2 has been found in hepato cellular tumors [7]. The LECT2 gene has been mapped to chromosome 5q31.1-q32 by fluorescence in situ hybridization. This region contains a cluster of cytokine genes that include IL-4, IL-5, and IL-9 [8].

Recently it was discovered that LECT2 may play an important role in insulin resistance and may promote atherosclerosis [9]. As such, it is also suggested to play a role in the development of fatty liver and obesity [10].

Hepatic amyloid, when identified, is usually located in the sinusoids, portal tracts, and arterioles. Various morphological patterns of amyloid including linear, globular and mixed types have been identified. The Globular Hepatic Amyloid (GHA) sub-type is composed of round to oval globules, 5 to 40 micrometer in diameter that are found within the space of Disse as well as aggregated within the portal tracts [11]. Chandran et al. found that GHA, although uncommon, is highly sensitive and specific for LECT2 amyloidosis and was also found more often in Hispanics [12]. LECT2 has been described in a patient with non-cirrhotic portal HTN [13]. It is possible that deposition of GHA in the vascular spaces of the liver can cause obstruction of the blood flow at the sinusoidal level resulting in non-cirrhotic portal hypertension [14].

The diagnosis of LECT2 amyloid involves the use of immuno histochemical staining and laser micro dissection with mass spectrometry (more accurate) in addition to demonstrating typical green birefringence in Congo-Red stained sections [15,16].

Being a newly discovered protein fibril that causes amyloidosis, the current state of knowledge regarding LECT2 and liver disease is a work in progress. More research is needed to clarify its role and significance regarding hepatic amyloidosis. Clinicians should be aware of its potential role as a cause of hepatic and renal disease (especially in Hispanics) and special tests such as immunostaining and laser micro dissection with mass spectrometry should be performed in cases where routine testing fails to characterize the amyloid fibril type.

References

  1. Larsen CP, Beggs ML, Wilson JD, Lathrop SL. Prevalence and organ distribution of leukocyte chemotactic factor 2 amyloidosis (ALECT2) among decedents in New Mexico. Amyloid. 2016; 23: 119-23.
  2. Benson MD, James S, Scott K, Liepnieks JJ, Kluve-Beckerman B. Leukocyte chemotactic factor 2: A novel renal amyloid protein. Kidney Int. 2008; 74: 218-222.
  3. Jimenez-Zepeda VH, Leung N. ALECT2 amyloidosis: a new type of systemic amyloid highly prevalent in the Hispanic population. Rev Invest Clin. 2014; 66: 269-273.
  4. Larsen CP, Walker PD, Weiss DT, Solomon A. Prevalence and morphology of leukocyte chemotactic factor 2-associated amyloid in renal biopsies. Kidney Int. 2010; 77: 816-819.
  5. Khalighi MA, Yue A, Hwang MT, Wallace WD. Leukocyte chemotactic factor 2 (LECT2) amyloidosis presenting as pulmonary-renal syndrome: a case report and review of the literature. Clin Kidney J. 2013; 6: 618-621.
  6. Mereuta OM, Theis JD, Vrana JA, Law ME, Grogg KL, Dasari S, et al. Leukocyte cell-derived chemotaxin 2 (LECT2)-associated amyloidosis is a frequent cause of hepatic amyloidosis in the United States. Blood. 2014; 123: 1479-1482.
  7. Zheng H, Miyakawa T, Sawano Y, Yamagoe S, Tanokura M. Crystallization and preliminary X-ray analysis of human leukocyte cell-derived chemotaxin 2 (LECT2). Acta Crystallogr Sect F Struct Biol Cryst Commun. 2013; 69: 316-319.
  8. Yamagoe S, Kameoka Y, Hashimoto K, Mizuno S, Suzuki K. Molecular cloning, structural characterization, and chromosomal mapping of the human LECT2 gene. Genomics. 1998; 48: 324-329.
  9. Hwang HJ, Jung TW, Hong HC, Seo JA, Kim SG, Kim NH, et al. LECT2 induces atherosclerotic inflammatory reaction via CD209 receptor-mediated JNK phosphorylation in human endothelial cells. Metabolism. 2015; 64: 1175-1182.
  10. Lebensztejn DM, Flisiak-Jackiewicz M, Białokoz-Kalinowska I, Bobrus-Chociej A, Kowalska I. Hepatokines and non-alcoholic fatty liver disease. Acta Biochim Pol. 2016.
  11. Kanel GC, Uchida T, Peters RL. Globular hepatic amyloid - an unusual morphologic presentation. Hepatology. 1981; 1: 647-652.
  12. Chandan VS, Shah SS, Lam-Himlin DM, Petris GD, Mereuta OM, Dogan A, et al. Globular hepatic amyloid is highly sensitive and specific for LECT2 amyloidosis. Am J Surg Pathol. 2015; 39: 558-564.
  13. Damlaj M, Amre R, Wong P, How J. Hepatic ALECT-2 amyloidosis causing portal hypertension and recurrent variceal bleeding: a case report and review of the literature. Am J Clin Pathol. 2014; 141: 288-291.
  14. Wanless IR. Micronodular transformation (nodular regenerative hyperplasia) of the liver: a report of 64 cases among 2,500 autopsies and a new classification of benign hepatocellular nodules. Hepatology. 1990; 11: 787-797.
  15. Comenzo RL. LECT2 makes the amyloid list. Blood. 2014; 123: 1436-1437.
  16. Paueksakon P, Fogo AB, Sethi S. Leukocyte chemotactic factor 2 amyloidosis cannot be reliably diagnosed by immunohistochemical staining. Hum Pathol. 2014; 45: 1445-1450.

Download PDF

Citation: Richards RJ and Nadir A. LECT2 – A New Cause of Hepatic Amyloidosis. Austin Liver. 2016; 1(1): 1001.

Home
Journal Scope
Online First
Current Issue
Editorial Board
Instruction for Authors
Submit Your Article
Contact Us