• DOI:10.1080/13506120802193811
• Corpus ID: 37061601

Thesis Report

@article{Arvin2008ThesisR,
  title={Thesis Report},
  author={Stefanus Arvin},
  journal={Amyloid},
  year={2008},
  volume={15},
  pages={216 - 217}
}

• S. Arvin
• Published 1 January 2008
• Medicine, Biology
• Amyloid

After a short introduction, this thesis starts in Chapter 2 with the description of the development of a new, reproducible, and fully monoclonal enzyme-linked immunosorbent assay (ELISA) for the quantification of serum amyloid A protein (SAA). The lowest detection limit of the assay was 8 mg/l allowing its use in biological fluids and in in vitro studies. The 95% upper limit of the basal reference interval for serum of healthy controls was 4.3 mg/l. SAA and C-reactive protein (CRP) concentrations differed among diseases and SAA concentrations were relatively higher than CRP especially in patients treated with glucocorticoids. In Chapter 3 the new ELISA was used for the quantification of amyloid A protein in guanidine extracts of aspirated subcutaneous abdominal fat tissue. The concentrations in 24 patients with arthritis and AA amyloidosis were higher than in controls without arthritis, controls with uncomplicated rheumatoid arthritis, and controls with other types of systemic amyloidosis. The upper reference limit of controls without AA amyloidosis appeared to be 11.6 ng/mg fat tissue. Patients with extensive deposits, as reflected by semiquantitatively assessed fat smears stained with Congo red, had higher amyloid A protein concentrations than patients with minute deposits. In Chapter 4, fat tissue specimens of 112 Egyptian patients with longstanding rheumatoid arthritis were screened for the presence of amyloid by Congo redstained smears. Eight patients appeared to have amyloid deposits in their fat tissue, resulting in a prevalence of amyloid in Egyptian patients with longstanding rheumatoid arthritis of about 7%. Quantification of the concentration of amyloid A protein in fat by ELISA (using the upper reference level that had been established in Dutch controls) identified six of the eight patients with AA amyloidosis, whereas none of the remaining 104 patients had increased concentrations. Contrary to the expectations, proteinuria was not a discriminating feature in the eight patients, whereas long disease duration, constipation, bronchopulmonary symptoms, and a moderate to low number of red blood cells might help to identify the arthritis patients with amyloid in this population. In Chapter 5, the diagnostic performance of the ELISA for quantification of amyloid A protein in fat tissue was studied in 154 of 183 patients with clinical AA amyloidosis and in 354 controls. Amyloid A protein quantification in fat tissue proved to be a sensitive (84%) and specific (99%) detection method. Advantages are its independence from staining quality and observer experience, the direct confirmation of amyloid AA type, and its potential for quantitative monitoring of tissue amyloid over time. Amyloid A protein quantification and semiquantitative Congo red grading were concordant. Men had lower amyloid A protein values than women and patients with familial Mediterranean fever (FMF) had lower values than patients with arthritis or other inflammatory diseases. These remarkable differences between both sexes and between inflammatory diseases cannot be explained easily. The capacity of fat cells to produce SAA as well as the mechanisms that produce and deposit amyloid A fibrils in fat tissue may be influenced directly by sex hormones and cytokines. This seems to be an interesting area for future fundamental research. In Chapter 6, serum amyloid P component (SAP) was isolated on a column of pyruvate-rich agarose from the blood of healthy donors. The method turned out to be effective and the purity of isolated SAP was high (499%), so the isolated SAP was suitable for use in scintigraphy studies of patients with systemic amyloidosis. In Chapter 7, kinetic turnover studies of ISAP were performed in 49 patients with systemic amyloidosis of the AA and AL types. Systemic amyloidosis was characterized by accelerated initial clearance of I-SAP from plasma and increased interstitial exchange rate and extravascular retention. These findings reflect reversible binding of radiolabeled SAP to amyloid deposits and provide clinically useful information for diagnosis, monitoring of the effect of therapy and for the assessment of the prognosis in patients with systemic amyloidosis. Amyloid, September 2008; 15(3): 216–217