Apolipoprotein A-1-related Amyloidosis 2 Case Reports And Review Of The Literature

Objective:Amyloidosis is a group of heterogeneous diseases caused by extracellular deposition of amyloid proteins in various organs,resulting in organ failure.Amyloid type is classified according to the fibril protein,and some 36 different proteins areknown to form amyloid fibrils in vivo.Apolipoprotein A-1(Apo A-1)amyloidosis is a rare type of amyloidosis.According to the statistics,ApoA-1 amyloidosis is accounted for only 0.2%of the systemic amyloidosis.Only isolated case reports have described this disease.There is no systematic understanding of the pathogenesis,the clinical manifestations and d iagnosis of the disease.Here we describe these two cases with ApoA-1 amylo idosis.We also,review the literature and discuss the improvement in the diagnosis and treatment of ApoA-1 amyloidosis.Methodology:We reported two cases with biopsy-proven ApoA-1 amyloidosis and retrospectively analyzed the clinical manifestation,pathological characteristics and response to treatment of this disease.Besides,we use laser microdissection and mass spectrometry studies to identify the amyloid type and the amyloidosis subtype was confirmed based on the most abundant amyloid protein.Besides,genetic testing was used to identify the amyloid type and reveal the genetic traits of two patients.The clinicopathological features of ApoA-1 amyloidosis and its response to treatment were further analyzed by literature reviewResults:Case 1 was a 64-year-old man suffering from nephrotic syndrome.The plasma levels of high-density lipoprotein(HDL)and ApoA-1 were normal.Rena biopsies revealed amyloidosis with extensive glomerular,interstitial and vascular involvement;and Congo red staining of above-mentioned areas showed the characteristic apple green birefringence under crossed polarized light.Both diffuse interstitial amyloid deposition(as stained with the antibody against ApoA-1)and the deposition of phospholipase A2 receptor antibodies(IgG1,IgG3 and/or IgG4)in the form of granules in the glomerular capillary loop as shown by enhanced immunofluorescence staining.Case 2 was a 40-year-old man presenting with nephrotic syndrome,splenomegaly and low plasma levels of HDL and ApoA-1.He had a positive family history and renal biopsy showed amyloid deposits in the mesangium according to Congo red staining,and amyloid deposition was shown by immunofluorescence staining using the antibody against ApoA-1.Proteomic analysis of amyloid deposits by mass spectrometry confirmed that ApoA-1 was the major protein in the deposits in both cases.Genetic analysis revealed that no mutation of the APOA1 gene was found in case 1 but case 2 carried a heterozygous mutation in APOA1 gene that resulted in amyloidogenic Trp50Arg ApoA-1 variant.Case 1 was treated with glucocorticoid combined with cyclosporine A.Case 2 was treated with calcitriol and angiotensin converting enzyme inhibitors.Two cases were followed up for 5 months and 2 years,respectively;and case 1 was found to have attenuated proteinuria while case 2 had an elevation of cholestasis indices along with renal insufficiency.Conclusion:ApoA-1 amyloidosis is an easily missed or misdiagnosed disease.Kidney is the one of mainly damage organs.Patients with renal and other organ involvements,especially with a family history of amyloidosis disease and low plasma levels of ApoA-1 should undergo renal biopsy immediately.Immunofluorescence staining and proteomic analysis by mass spectrometry of the amyloid deposits combined with genetic analysis can provide accurate diagnosis of amyloid subtypes.