We have located links that may give you full text access.
Apolipoprotein CII Amyloidosis Associated With p.Lys41Thr Mutation.
KI Reports 2018 September
Introduction: Apolipoprotein CII amyloidosis (AApoCII) is a rare form of amyloidosis. Here, we report a novel mutation associated with AApoCII amyloidosis in 5 patients and describe their clinical, renal biopsy, and mass spectrometry findings.
Methods: Five patients with renal AApoCII p.Lys41Thr amyloidosis were identified from our amyloid mass spectrometry cohort. Clinical features, kidney biopsy, and mass spectrometry findings were analyzed in this rare type of amyloidosis.
Results: The patients were older adults (mean age of 71.6 years at diagnosis), presented with nephrotic-range proteinuria, and often had declining renal function. All renal biopsy specimens showed massive mesangial nodules composed of weakly eosinophilic, periodic acid-Schiff negative, Congo red-positive amyloid deposits. There were no interstitial, vascular, or medullary deposits. In all cases, immunofluorescence studies were negative for Igs and electron microscopy showed amyloid fibrils. Proteomic analysis of Congo red-positive amyloid deposits detected large amounts of apolipoprotein CII (APOC2) protein. We also detected APOC2 p.Lys41Thr mutant protein in amyloid deposits of all patients. DNA sequencing in 1 patient confirmed the presence of the mutation. Both mutant and wild-type forms of APOC2 were detected in amyloid deposits of all patients. Molecular dynamic simulations showed the variant mediating a collapse of the native structure of APOC2, thereby destabilizing the protein.
Conclusion: We propose that AApoCII p.Lys41Thr amyloidosis is a new form of amyloidosis seen in elderly individuals, histologically exhibiting massive glomerular involvement, leading to nephrotic-range proteinuria and progressive chronic kidney disease.
Methods: Five patients with renal AApoCII p.Lys41Thr amyloidosis were identified from our amyloid mass spectrometry cohort. Clinical features, kidney biopsy, and mass spectrometry findings were analyzed in this rare type of amyloidosis.
Results: The patients were older adults (mean age of 71.6 years at diagnosis), presented with nephrotic-range proteinuria, and often had declining renal function. All renal biopsy specimens showed massive mesangial nodules composed of weakly eosinophilic, periodic acid-Schiff negative, Congo red-positive amyloid deposits. There were no interstitial, vascular, or medullary deposits. In all cases, immunofluorescence studies were negative for Igs and electron microscopy showed amyloid fibrils. Proteomic analysis of Congo red-positive amyloid deposits detected large amounts of apolipoprotein CII (APOC2) protein. We also detected APOC2 p.Lys41Thr mutant protein in amyloid deposits of all patients. DNA sequencing in 1 patient confirmed the presence of the mutation. Both mutant and wild-type forms of APOC2 were detected in amyloid deposits of all patients. Molecular dynamic simulations showed the variant mediating a collapse of the native structure of APOC2, thereby destabilizing the protein.
Conclusion: We propose that AApoCII p.Lys41Thr amyloidosis is a new form of amyloidosis seen in elderly individuals, histologically exhibiting massive glomerular involvement, leading to nephrotic-range proteinuria and progressive chronic kidney disease.
Full text links
Related Resources
Trending Papers
Challenges in Septic Shock: From New Hemodynamics to Blood Purification Therapies.Journal of Personalized Medicine 2024 Februrary 4
Molecular Targets of Novel Therapeutics for Diabetic Kidney Disease: A New Era of Nephroprotection.International Journal of Molecular Sciences 2024 April 4
Perioperative echocardiographic strain analysis: what anesthesiologists should know.Canadian Journal of Anaesthesia 2024 April 11
The 'Ten Commandments' for the 2023 European Society of Cardiology guidelines for the management of endocarditis.European Heart Journal 2024 April 18
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app