Clinicopathologic Characteristics for Leukocyte Cell-Derived Chemotaxin 2-Associated Amyloidosis
Amyloidosis derived from leukocyte cell-derived chemotaxin 2 (ALECT2) is a newly recognized form of amyloidosis. It has already been established as a frequent form of systemic amyloidosis in the United States, with predominant involvement of the kidney and liver.
Mayo Clinic researchers, first author Samih Nasr, M.D., Consultant, Division of Anatomic Pathology, and Associate Professor of Laboratory Medicine and Pathology, reviewed recent Mayo Clinic and non-Mayo Clinic studies to establish the clinicopathologic characteristics, incidence, and outcome of amyloidosis derived from ALECT2.
According to the findings from the review in the Clinical Journal of the American Society of Nephrology, the disease has a strong ethnic bias, with 88 to 92 percent of diagnosed patients being ofHispanic origin (particularly Mexicans). Additional ethnic groups prone to develop ALECT2 include Punjabis (people from Pakistan and northern India), First Nations people in British Columbia (various Aboriginal people in Canada who are neither Inuit nor Métis), and Native Americans. The majority of these patients are elderly and present with chronic renal insufficiency and bland urinary sediment.
According to Dr. Nasr, “Clinicians and pathologists should maintain a high level of suspicion for ALECT2 amyloidosis in older individuals of Hispanic origin who present with renal impairment and bland urinary sediment—regardless of the degree of proteinuria—and a Congo red stain should be performed.”
Key findings from the review include:
- ALECT2 accounts for 2.7 to 10 percentof cases of renal amyloidosis in the United States and for 25 percent of cases of liver ALECT2 amyloidosis diagnosed by proteomics.
- Most patients present with chronic renal insufficiency with a mean serum creatinine at diagnosis of 3 mg/dl. In contrast to other forms of renal amyloidosis, proteinuria is an inconsistent finding in renal ALECT2 amyloidosis and is lacking in 21 to 67 percent of patients.
- Histologically, ALECT2 deposits show a preferential involvement of cortical interstitium in the kidney and periportal and pericentral vein regions in the liver.
- Concurrent renal disease is not uncommon (present in one-third of cases), which may contribute to the renal insufficiency and proteinuria and may adversely impact renal prognosis.
The findings also indicate that a minority of ALECT2 patients have concurrent monoclonal gammopathy, highlighting the importance of accurate typing of amyloid deposits to avoid misdiagnosing ALECT2 amyloidosis as amyloid light-chain (AL) amyloidosis and avoid unnecessary and harmful chemotherapy.
“Typing of amyloid deposits by liquid chromatography and mass spectrometry-based proteomics is the best tool to diagnose ALECT2 amyloidosis and other forms of amyloidosis because of its high sensitivity and specificity and because it is a single test that can detect the culprit protein in contrast to IHC (immunohistochemical) typing of amyloidosis, which requires staining for multiple antibodies using several tissue sections,” says Dr. Nasr.
Patient survival is excellent, likely due to the rarity of cardiac involvement, whereas renal survival is guarded, with a median renal survival of 62 months in those without concurrent renal disease.
While there is currently no efficacious therapy for ALECT2 amyloidosis, renal transplantation seems to be a reasonable treatment for patients with advanced renal failure, although the disease may recur in the allograft.
The pathogenesis of ALECT2 has not yet been clarified. “Further studies are needed to elucidate the pathogenesis of ALECT2 amyloidosis in order to develop specific therapy,” adds Dr. Nasr.