Abstract
Serum amyloid A (SAA), a plasma precursor of reactive amyloid deposits, is a multigene product. SAA1 and SAA2, with primary structures that are 93% identical (98 of 104 amino acids), behave as acute phase proteins, as demonstrated by their increasing levels in plasma. Heretofore, it has been understood that SAA1 predominates and functions as an isotype in plasma. However, accurate measurements differentiating the two isotypes have not been reported. In this study, using monoclonal antibodies specific for SAA1, we developed an enzyme-linked immunosorbent assay (ELISA) for SAA1. The levels and ratios of SAA1 in total SAA (TSAA) were investigated in healthy subjects and patients with rheumatoid arthritis (RA). The SAA1/TSAA ratio was 74±12% and 77±12% in healthy subjects and RA patients, respectively. In RA patients, the ratios were not influenced by SAA1 genotype, which has been proposed to affect plasma SAA values. The kinetics of SAA1 in inflamed patients undergoing hemodialysis was found to be parallel with total SAA and C-reactive protein. Finally, this study confirmed that SAA1 is a major isotype of acute phase SAA and may determine total SAA values. This specific assay could be used in the evaluation of SAA behavior in several clinical conditions.
References
1. Husby G, Marhaug G, Dowton B, Sletten K, Sipe JD. Serum amyloid A (SAA). Biochemistry, genetics and the pathogenesis of AA amyloidosis. Amyloid 1994; 1:119–37.10.3109/13506129409148635Search in Google Scholar
2. Sipe JD. Revised nomenclature for serum amyloid A. Nomenclature Committee of the International Society of Amyloidosis. Part 2. Amyloid 1999; 6:67–70.10.3109/13506129908993291Search in Google Scholar
3. Yamada T. Serum amyloid A (SAA). A concise review of biology, assay methods and clinical usefulness. Clin Chem Lab Med 1999; 37:381–8.10.1515/CCLM.1999.063Search in Google Scholar
4. Thorn CF, Whitehead AS. Differential glucocorticoid enhancement of the cytokine-driven transcriptional activation of the human acute phase serum amyloid A genes, SAA1 and SAA2. J Immunol 2002; 169:399–406.10.4049/jimmunol.169.1.399Search in Google Scholar
5. Strachan AF, de Beer FC, van der Westhuyzen DR, Coetzee GA. Identification of three isoform patterns of human serum amyloid A protein. Biochem J 1988; 250:203–7.10.1042/bj2500203Search in Google Scholar
6. Yamada T, Hirano N, Kuroda T, Okuda Y, Itoh Y. Generation and characterization of rat monoclonal antibodies against human serum amyloid A. Scand J Immunol 1997; 46:175–9.10.1046/j.1365-3083.1997.d01-108.xSearch in Google Scholar
7. Yamada T, Wada A, Itoh Y, Itoh K. Serum amyloid A1 alleles and plasma concentrations of serum amyloid A. Amyloid 1999; 6:199–204.10.3109/13506129909007327Search in Google Scholar
8. Yamada T, Okuda Y, Takasugi K, Itoh K, Igari J. Relative serum amyloid A (SAA) values: the influence of SAA1 genotypes and corticosteroid treatment in Japanese patients with rheumatoid arthritis. Ann Rheum Dis 2001; 60:124–7.10.1136/ard.60.2.124Search in Google Scholar
9. Yamada T, Kluve-Beckerman B, Liepnieks JJ, Benson MD. Fibril formation from recombinant serum amyloid A. Biochim Biophys Acta 1994; 1226:323–9.10.1016/0925-4439(94)90044-2Search in Google Scholar
10. Yamada T, Wada A, Itoh K, Igari J. Serum amyloid A secretion from monocytic leukaemia cell line THP-1 and cultured human peripheral monocytes. Scand J Immunol 2000; 52:7–12.10.1046/j.1365-3083.2000.00734.xSearch in Google Scholar PubMed
11. Yamada T, Uchiyama K, Yakata M, Geiyo F. Sandwich enzyme immunoassay for serum amyloid A protein (SAA). Clin Chim Acta 1989; 179:169–76.10.1016/0009-8981(89)90163-0Search in Google Scholar
12. Yamada T, Wada A. Slower clearance of human SAA1.5 in mice: implications for allele specific variation of SAA concentration in human. Amyloid 2003; 10:147–50.10.3109/13506120308998996Search in Google Scholar PubMed
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