Effect of etanercept on serum amyloid A protein (SAA) levels in patients with AA amyloidosis complicating inflammatory arthritis

2008 ◽  
Vol 27 (7) ◽  
pp. 923-925 ◽  
Author(s):  
M. E. Perry ◽  
Anne Stirling ◽  
J. A. Hunter
Keyword(s):  
Inflammatory Arthritis ◽  
Serum Amyloid A ◽  
Serum Amyloid ◽  
Aa Amyloidosis ◽  
Amyloid A ◽  
Serum Amyloid A Protein

scholarly journals Aggregation of Mouse Serum Amyloid A Protein Was Promoted by Amyloid-Enhancing Factors with the More Genetically Homologous Serum Amyloid A

2021 ◽  
Vol 22 (3) ◽  
pp. 1036
Author(s):  
Xuguang Lin ◽  
Kenichi Watanabe ◽  
Masahiro Kuragano ◽  
Kiyotaka Tokuraku
Keyword(s):  
Amino Acid ◽  
Serum Amyloid A ◽  
Animal Species ◽  
Amino Acid Sequences ◽  
Serum Amyloid ◽  
Mouse Serum ◽  
Aa Amyloidosis ◽  
Basic Residue ◽  
Amyloid A ◽  
Serum Amyloid A Protein

Amyloid A (AA) amyloidosis is a condition in which amyloid fibrils characterized by a linear morphology and a cross-β structure accumulate and are deposited extracellularly in organs, resulting in chronic inflammatory diseases and infections. The incidence of AA amyloidosis is high in humans and several animal species. Serum amyloid A (SAA) is one of the most important precursor amyloid proteins and plays a vital step in AA amyloidosis. Amyloid enhancing factor (AEF) serves as a seed for fibril formation and shortens the onset of AA amyloidosis sharply. In this study, we examined whether AEFs extracted and purified from five animal species (camel, cat, cattle, goat, and mouse) could promote mouse SAA (mSAA) protein aggregation in vitro using quantum-dot (QD) nanoprobes to visualize the aggregation. The results showed that AEFs shortened and promoted mSAA aggregation. In addition, mouse and cat AEFs showed higher mSAA aggregation-promoting activity than the camel, cattle, and goat AEFs. Interestingly, homology analysis of SAA in these five animal species revealed a more similar amino acid sequence homology between mouse and cat than between other animal species. Furthermore, a detailed comparison of amino acid sequences suggested that it was important to mSAA aggregation-promoting activity that the 48th amino acid was a basic residue (Lys) and the 125th amino acid was an acidic residue (Asp or Glu). These data imply that AA amyloidosis exhibits higher transmission activity among animals carrying genetically homologous SAA gene, and may provide a new understanding of the pathogenesis of amyloidosis.

Amyloid load and clinical outcome in AA amyloidosis in relation to circulating concentration of serum amyloid A protein

The Lancet ◽  
2001 ◽  
Vol 358 (9275) ◽  
pp. 24-29 ◽  
Author(s):  
Julian D Gillmore ◽  
Laurence B Lovat ◽  
Malcolm R Persey ◽  
Mark B Pepys ◽  
Philip N Hawkins
Keyword(s):  
Clinical Outcome ◽  
Serum Amyloid A ◽  
Serum Amyloid ◽  
Aa Amyloidosis ◽  
Amyloid A ◽  
Serum Amyloid A Protein ◽  
Amyloid Load

scholarly journals Cryo-EM structure of an amyloid fibril from systemic amyloidosis

2018 ◽  
Author(s):  
Falk Liberta ◽  
Sarah Loerch ◽  
Matthies Rennegarbe ◽  
Angelika Schierhorn ◽  
Per Westermark ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Serum Amyloid A ◽  
Amyloid Fibril ◽  
Ex Vivo ◽  
Serum Amyloid ◽  
Aa Amyloidosis ◽  
Amyloid A ◽  
Serum Amyloid A Protein ◽  
N Terminus

AbstractSystemic AA amyloidosis is a worldwide occurring disease of humans and animals that arises from the misfolding of serum amyloid A protein. To provide insights into the molecular basis of this disease we used electron cryo-microscopy and determined the structure of an ex vivo amyloid fibril purified from AA amyloidotic mice at 3.0 Å resolution. The fibril consists of C-terminally truncated serum amyloid A protein arranged into a compactly folded all-β conformation. The structure identifies the protein N-terminus as central for the assembly of this fibril and provides a mechanism for its prion-like replication. Our data further explain how amino acid substitutions within the tightly packed fibril core can lead to amyloid resistance in vivo.

Serum amyloid A protein forms a complex with a fragment of Apolipoprotein A-I in the domestic blue fox: a protective mechanism against AA amyloidosis?

Amyloid ◽  
2004 ◽  
Vol 11 (3) ◽  
pp. 184-190 ◽  
Author(s):  
Ellen Johanne Elisen ◽  
Cathrine Foyn Bruun ◽  
Knut Nordstoga ◽  
Gunnar Husby ◽  
Knut Sletten
Keyword(s):  
Serum Amyloid A ◽  
Serum Amyloid ◽  
Protective Mechanism ◽  
Aa Amyloidosis ◽  
Amyloid A ◽  
Apolipoprotein A ◽  
Serum Amyloid A Protein ◽  
Blue Fox

scholarly journals AB0072 SERUM AMYLOID A PROTEIN (SAA) IN ANKYLOSING SPONDYLITIS AND THE RELATIONSHIP WITH SYSTEMIC INFLAMMATION

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1066.2-1066
Author(s):  
K. Sakharova ◽  
M. Cherkasova ◽  
S. Erdes
Keyword(s):  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Serum Amyloid A ◽  
Inflammatory Diseases ◽  
Strong Association ◽  
Critical Role ◽  
Serum Amyloid ◽  
Aa Amyloidosis ◽  
Amyloid A ◽  
Serum Amyloid A Protein

Background:Serum amyloid A protein (SAA) likely has a critical role in control and possibly propagation of the primordial acute phase response and is the precursor of AA amyloid fibrils. Prolonged elevations in SAA are the major inciting factor for AA amyloidosis developing in chronic inflammatory diseases. In Russia 2-4% of patients with ankylosing spondylitis (AS) have secondary (AA) amyloidosis.Objectives:To study the level of SAA in AS its relationship with indicators of disease activity.Methods:124 patients with AS (according to mNYC 1984) 70 men, 54 women, of whom HLA B 27 positive 91.1% mean age 38.1 (± 12.9), age at the onset of the disease 23.5 (± 9.9) consecutively admitted to the clinic of the Research Institute rheumatology from February to November 2020. In addition to the standard examination (the median CRP 6.7 mg/l [1.4; 24.9], ESR 13 mm/h [7; 27], SAA was studied in all patients by the nephelometric method.Results:The median SAA in 124 patients was 12.5 mg/l [4;71.6]. Among them, 31% had normal SAA level (<5 mg/l), and 69 % - more than 5 mg/l. In 21 (17.5 %) cases, the level of SAA was increased at normal CRP levels, and only in 2 cases an increase in the level of CRP at normal SAA levels; 50 patients (40.3 %) with normal ESR had elevated SAA levels, and 7 (5.6%) - ESR exceeded the upper limits of the norm with normal SAA levels. Comparison of the average values of the levels of SAA, CRP, ESR in men and women did not reveal significant differences between them. The SAA level was weakly correlated with ESR (r = 0.2; p=0.002) and BASDAI (r=0.3; p=0.002), moderately with ASDAS-CRP (r=0.5; r<0.0001), but showed a strong association with CRP (r = 0.80; p<0.00001). Patients with elevated SAA levels (>5 mg/l) had a shorter disease duration (10 and 12 year; p<0.0004), higher ASDAS-CRP (2.9 and 2.4; p<0.003), blood CRP level (14.6 and 1.3; p<0.00001), and significantly more peripheral arthritis (60% and 39%; p<0.05) than patients with normal indicators.Conclusion:The level of SAA correlates well with indicators of AS activity, especially with the level of CRP, and can be used as an alternative indicator of disease activity.Disclosure of Interests:None declared

scholarly journals Serum amyloid A forms stable oligomers that disrupt vesicles at lysosomal pH and contribute to the pathogenesis of reactive amyloidosis

2017 ◽  
Vol 114 (32) ◽  
pp. E6507-E6515 ◽  
Author(s):  
Shobini Jayaraman ◽  
Donald L. Gantz ◽  
Christian Haupt ◽  
Olga Gursky
Keyword(s):  
Serum Amyloid A ◽  
Major Complication ◽  
Lipid Vesicles ◽  
Serum Amyloid ◽  
High Density Lipoproteins ◽  
Aa Amyloidosis ◽  
Intrinsically Disordered ◽  
Amyloid A ◽  
Α Helix ◽  
Structural Methods

Serum amyloid A (SAA) is an acute-phase plasma protein that functions in innate immunity and lipid homeostasis. SAA is a protein precursor of reactive AA amyloidosis, the major complication of chronic inflammation and one of the most common human systemic amyloid diseases worldwide. Most circulating SAA is protected from proteolysis and misfolding by binding to plasma high-density lipoproteins. However, unbound soluble SAA is intrinsically disordered and is either rapidly degraded or forms amyloid in a lysosome-initiated process. Although acidic pH promotes amyloid fibril formation by this and many other proteins, the molecular underpinnings are unclear. We used an array of spectroscopic, biochemical, and structural methods to uncover that at pH 3.5–4.5, murine SAA1 forms stable soluble oligomers that are maximally folded at pH 4.3 with ∼35% α-helix and are unusually resistant to proteolysis. In solution, these oligomers neither readily convert into mature fibrils nor bind lipid surfaces via their amphipathic α-helices in a manner typical of apolipoproteins. Rather, these oligomers undergo an α-helix to β-sheet conversion catalyzed by lipid vesicles and disrupt these vesicles, suggesting a membranolytic potential. Our results provide an explanation for the lysosomal origin of AA amyloidosis. They suggest that high structural stability and resistance to proteolysis of SAA oligomers at pH 3.5–4.5 help them escape lysosomal degradation, promote SAA accumulation in lysosomes, and ultimately damage cellular membranes and liberate intracellular amyloid. We posit that these soluble prefibrillar oligomers provide a missing link in our understanding of the development of AA amyloidosis.

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