¹Belarusian State Medical University, Minsk, Belarus
²Institute of Genetics and Cytology, Belarusian National Academy of Sciences,Minsk, Belarus
*Corresponding author: Prof. Nikolay F. Soroka, PhD, ScD, Head of the 2nd Department of Internal Diseases, Belarusian State Medical University. 83, Dzerzhinsky avenue, 220116 Minsk, Belarus. Tel: 375-17-272-5793; Fax: 375-17-272-5793. E-mail: firstname.lastname@example.org
Background:. Secondary or acquired amyloidosis (AA) develops in patients with chronic infections and inflammatory diseases such as rheumatoid arthritis (RA). The detection of risk factors is one of the most important objectives that will help to improve the patient’s survival.
Methods and results: In this study, we observed 104 patients: 45 (1st group) with RA complicated by renal amyloidosis (histologically confirmed) and 59 RA patients without this complication (2nd group). All patients were Belarusian citizens. Patient’s previous medical history and data were analyzed. All patients had undergone tests for the detection of C. trachomatis infection. Urethra or cervical scrapes were analyzed by polymerase chain reaction (PCR) method and/or by cultural method; the presence of C. trachomatis G and M antibodies was detected by immunoenzyme assay. Further, we compared the influence of the SAA1 gene polymorphism in AA-positive RA patients with those in AA-negative RA. A statistical analysis was conducted to detect possible risk factors for developing renal amyloidosis secondary to RA. The odds ratio (OR) calculated for the SAA1 α/α genotype was 45.26 ( 95%CI: 9.9– 206.8). It was shown that the SAA1 α/α genotype dominated in both groups and consisted 95.6% (1st group) and 32.2% (2nd group), respectively. The OR for C. trachomatis infection was 26.6 (95%CI: 9.26–76.37). Further, we created a prognostic model to determine the risk factors for developing renal amyloidosis in patients with RA.
Conclusions: The risk of developing secondary amyloidosis in RA patients significantly depends on SAA1 genotype and the presence of C. trachomatis infection and can be evaluated using the prognostic model.
- Nasonov EL, Nasonova VA. Rheumayology: National guideline. Moscow, 2008.
- Hazenberg BP, van Rijswijk MH. Where has secondary amyloid gone? Ann Rheum Dis 2000; 59: P.577-579.
- Rochen C, Shakespeare A. Pathology, diagnosis and pathogenesis of AA amyloidosis. Virchows Arch. 2002; 440:111-122.
- Hazenberg BPC, van Rijswijk MH. Clinical and therapeutic aspects of AA amyloidosis. Baillieres Clin Rheumatol. 1994; 8:661-690.
- Misra R, Wakhlu A, Krishnani N, Hissaria P, Aggarwal A. Prevalence of silent amyloidosis in rheumatoid arthritis and its clinical significance. J Rheumatol 2004; 31:1013-1014.
- Bergesio F, Ciciani AM, Santostefano M, et al. Renal involvement in systemic amyloidosis – an Italian retrospective study on epidemiological and clinical data at diagnosis. Nephrol Dial Transplant. 2007; 22(6): 1608-1618.
- Okuda Y, Takasugi K. Diagnostic and prognostic study of secondary amyloidosis complicating rheumatoid arthritis. Amyloid and Amyloidosis. Parthenon Publishing Group, New York, 1998: 426-428.
- Toyoshima H, Kusaba T, Yamaguchi M. Cause of death in autopsied RA patients. Ryumachi. 1993; 33:209-214.
- Kobayashi H, Tada S, Fuchigami T, Okuda Y, Takasugi K, Matsumoto T, et al. Amyloidosis in rheumatoid arthritis: diagnostic and prognostic value of gastroduodenal biopsy. Br J Rheumatol. 1996; 35:44-49.
- Yamada T. Serum amyloid A (SAA): a concise review of biology, assay methods and clinical usefulness. Clinical Chemistry and Laboratory Medicine 1999; 37:381-388
- Malle E, deBeer FC. Human serum amyloid A (SAA) protein: a prominent acute-phase reactant for clinical practice. Eur J Clin Invest 1996; 26:427-435.
- Maury CP, Wegelius O. Clinical value of serum amyloid A and C-reactive protein measurements in secondary amyloidosis. Int J Tissue React 1985; 7:405-407.
- Steel DM, Whitehead AS. The major acute phase reactants: C-reactive protein, serum amyloid P component and serum amyloid A protein. Immunol Today 1994; 15:81-88.
- Uhlar CM, Whitehead AS. The kinetics and magnitude of the
synergistic activation of the serum amyloid A promoter by IL-1 beta and IL-6 is determined by the order of cytokine addition. Scand J Immunol 1999; 49:399-404.
- Migita K, Abiru S, Nakamura M, et al. Lipopolysaccharide signaling induces serum amyloid A (SAA) synthesis in human hepatocytes in vitro. FEBS Lett 2004; 569:235-239.
- Hutchinson WL, Noble GE, Hawkins PN, Pepys MB. The pentraxins, C-reactive protein and serum amyloid P component, are cleared and catabolized by hepatocyes in vivo. J Clin Invest 1994; 94:1390-1396.
- Kisilevsky R. The relation of proteoglycans, serum amyloid P and apo E to amyloidosis current status, 2000. Amyloid 2000; 7:23-25.
- Cunnane G, Grehan S, Geoghegan S, McCormack C, Shields D, Whitehead AS, et al. Serum amyloid A in the assessment of early inflammatory arthritis. J Rheumatol 2000; 27:58-63.
- Urieli-Shoval S, Reinhold L, Yaacov M. Expression and function of serum amyloid A, a major acute-phase protein, in normal and disease states. Curr. Opin. Hematol.2000; 7: 64-69.
- Baba S, Masago SA, Takahashi T et al. A novel allelic variant of serum amyloid A, SAA1γ: genomic evidence, evolution, frequency, and implication as a risk factor for reactive systemic AA-amyloidosis. Hum Mol Genet 1995; Vol. 4: 1083-1087.
- Moriguchi M, Terai C, Kaneko H, et al. A novel single-nucleotide polymorphism at the 5'-flanking region of SAA1 associated with risk of type AA amyloidosis secondary to rheumatoid arthritis. Arthritis Rheum 2001; 44:1266-1272.
- Sihvonen S, Korpela M, Mustonen J, Laippala P, Pasternack A. Renal disease as a predictor of increased mortality among patients with rheumatoid arthritis. Nephron Clin Pract 2004; 96:107-114.
- Sasatomi Y, Kiyoshi Y, Uesugi N, Hisano S, Takebayashi S. Prognosis of renal amyloidosis: a clinicopathological study using cluster analysis. Nephron. 2001; 87: 42-49.
- Tanaka F, Migita K, Honda S et al. Clinical outcome and survival of secondary (AA) amyloidosis. Clin Exp Rheumatol 2003; 21:343-346.
- Joss N, McLaughlin K, Simpson K, Boulton-Jones JAM. Presentation, survival and prognostic markers in AA amyloidosis. Q J Med 2000; 93:535-542.
- Kuroda T, Tanabe N, Harada T, et al. Long-term mortality outcome in patients with reactive amyloidosis associated with rheumatoid arthritis. Clin Rheumatol 2005; 3:1-8.
- Bely I, Apathy A. Systemic AA amyloidosis in rheumatoid arthritis - the influence of age, sex, onset and duration of disease. A retrospective study. In: EULAR 2001, HU0128.
- Immonen K, Savolainen A, Kautianen H, Hakala M. Longterm outcome of amyloidosis associated with juvenile idiopathic arthritis. J Rheumatol 2008; 35: 907-912.
- Soroka NF. Rheumatoid arthritis associated with C. trachomatis. Zdravoohranenie 2010; 1: 1-9.
- Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988; 31:315-324.
- Nakamura T, Higashi, Tomoda K, Tsukano M, Baba S, Shono M. Significance of SAA 1.3 allele genotype in Japanese patients with amyloidosis secondary to rheumatoid arthritis. Rheumatology 2006; 45:43-49.
- Booth DR, Booth SE, Gillmore JD. SAA1 alleles as risk factors in reactive systemic AA amyloidosis. Amyloid 1998; Vol. 5: 262-265.
- Mavragani CP, Yiannakouris N, Zintzaras E et al. Analysis of SAA1 gene polymorphisms in the Greek population: rheumatoid arthritis and FMF patients relative to normal control. Homogeneous distribution and low evidence of AA amyloidosis. Amyloid 2007; Vol. 14: 271-275.
- Yamada T, Okuda Y, Takasugi K, et al. An allele of serum amyloid A1 associated with amyloidosis in both Japanese and Caucasians. Amyloid. 2003; 10:7-11.
This article is based on “Risk factors of renal amyloidosis in patients with rheumatoid arthritis”( N.F. Soroka et al. International Journal of Biomedicine 2010; 1:14-23) and updated.
IJBM 2011; 1(2):87-96.©2011 International Medical Research and Development Corporation. All rights reserved.