Serum amyloid A

Jump to navigation Jump to search
Human Serum amyloid A1
Other data
LocusChr. 11 p15.1
Human Serum amyloid A2
Other data
LocusChr. 11 p15.1-p14
Human Serum amyloid A3, pseudogene
Alt. symbolsSAA3
Other data
LocusChr. 11 p15.1-p14
Human Serum amyloid A4
Alt. symbolsC-SAA
Other data
LocusChr. 11 p15.1-p14

Serum amyloid A (SAA) proteins are a family of apolipoproteins associated with high-density lipoprotein (HDL) in plasma. Different isoforms of SAA are expressed constitutively (constitutive SAAs) at different levels or in response to inflammatory stimuli (acute phase SAAs). These proteins are produced predominantly by the liver.[1] The conservation of these proteins throughout invertebrates and vertebrates suggests that SAAs play a highly essential role in all animals.[2]

Acute-phase serum amyloid A proteins

Acute-phase serum amyloid A proteins (A-SAAs) are secreted during the acute phase of inflammation. These proteins have several roles, including the transport of cholesterol to the liver for secretion into the bile, the recruitment of immune cells to inflammatory sites, and the induction of enzymes that degrade extracellular matrix. A-SAAs are implicated in several chronic inflammatory diseases, such as amyloidosis, atherosclerosis, and rheumatoid arthritis.[3] Three acute-phase SAA isoforms have been reported in mice, called SAA1, SAA2, and SAA3. During inflammation, SAA1 and SAA2 are expressed and induced principally in the liver, whereas SAA3 is induced in many distinct tissues. SAA1 and SAA2 genes are regulated in liver cells by the proinflammatory cytokines IL-1, IL-6, and TNF-α. Both SAA1 and SAA2 are induced up to a 1000-fold in mice under acute inflammatory conditions following exposure to bacterial lipopolysaccharide (LPS).[3] Three A-SAA genes have also been identified in humans,[4] although the third gene, SAA3, is believed to represent a pseudogene that does not generate messenger RNA or protein.[5] Molecular weights of the human proteins are estimated at 11.7 kDa for SAA1[6] and 12.8 kDa for SAA4.[7]

Serum amyloid A (SAA) is also an acute phase marker that responds rapidly. Similar to CRP, levels of acute-phase SAA increase within hours after inflammatory stimulus, and the magnitude of increase may be greater than that of CRP. Relatively trivial inflammatory stimuli can lead to SAA responses. It has been suggested that SAA levels correlate better with disease activity in early inflammatory joint disease than do ESR and CRP. Although largely produced by hepatocytes, more recent studies show that SAA is produced by adipocytes as well, and its serum concentration is associated with body mass index.[8]

Constitutive serum amyloid A proteins

A fourth SAA (SAA4) was identified in humans and is expressed constitutively in the liver and, thus, is defined as a constitutive SAA (C-SAA).[9] A similar protein that is now also called SAA4 has since been identified in the mouse; it had originally been designated SAA5.[10][11]


  1. Uhlar CM, Whitehead AS (October 1999). "Serum amyloid A, the major vertebrate acute-phase reactant". European Journal of Biochemistry. 265 (2): 501–23. doi:10.1046/j.1432-1327.1999.00657.x. PMID 10504381.
  2. Manley PN, Ancsin JB, Kisilevsky R (2006). "Rapid recycling of cholesterol: the joint biologic role of C-reactive protein and serum amyloid A". Medical Hypotheses. 66 (4): 784–92. doi:10.1016/j.mehy.2005.10.018. PMID 16337748.
  3. 3.0 3.1 Zhang N, Ahsan MH, Purchio AF, West DB (June 2005). "Serum amyloid A-luciferase transgenic mice: response to sepsis, acute arthritis, and contact hypersensitivity and the effects of proteasome inhibition". Journal of Immunology. 174 (12): 8125–34. doi:10.4049/jimmunol.174.12.8125. PMID 15944321.
  4. Betts JC, Edbrooke MR, Thakker RV, Woo P (October 1991). "The human acute-phase serum amyloid A gene family: structure, evolution and expression in hepatoma cells". Scandinavian Journal of Immunology. 34 (4): 471–82. doi:10.1111/j.1365-3083.1991.tb01570.x. PMID 1656519.
  5. Kluve-Beckerman B, Drumm ML, Benson MD (November 1991). "Nonexpression of the human serum amyloid A three (SAA3) gene". DNA and Cell Biology. 10 (9): 651–61. doi:10.1089/dna.1991.10.651. PMID 1755958.
  8. Pincus MR; McPherson RA; Henry JB (2007). Henry's Clinical Diagnosis and Management by Laboratory Methods. Saunders Elsevier. ISBN 1-4160-0287-1.
  9. Steel DM, Sellar GC, Uhlar CM, Simon S, DeBeer FC, Whitehead AS (May 1993). "A constitutively expressed serum amyloid A protein gene (SAA4) is closely linked to, and shares structural similarities with, an acute-phase serum amyloid A protein gene (SAA2)". Genomics. 16 (2): 447–54. doi:10.1006/geno.1993.1209. PMID 7686132.
  10. de Beer MC, Kindy MS, Lane WS, de Beer FC (February 1994). "Mouse serum amyloid A protein (SAA5) structure and expression". The Journal of Biological Chemistry. 269 (6): 4661–7. PMID 8308037.
  11. de Beer MC, de Beer FC, Gerardot CJ, Cecil DR, Webb NR, Goodson ML, Kindy MS (May 1996). "Structure of the mouse Saa4 gene and its linkage to the serum amyloid A gene family". Genomics. 34 (1): 139–42. doi:10.1006/geno.1996.0253. PMID 8661036.

Amyloidosis Microchapters


Patient Information


Historical Perspective


Primary amyloidosis
Secondary amyloidosis
Familial amyloidosis
Wild-type (senile) amyloidosis
Cardiac amyloidosis
Beta-2 microglobulin related amyloidosis
Gelsolin related amyloidosis
Lysozyme amyloid related amyloidosis
Leucocyte cell-derived chemotaxin 2 related amyloidosis
Fibrinogen A alpha-chain associated amyloidosis



Differentiating Amyloidosis from other Diseases

Epidemiology and Demographics

Risk Factors


Natural History, Complications and Prognosis


Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings



Echocardiography and Ultrasound

CT scan


Other Imaging Findings

Other Diagnostic Studies


Medical Therapy


Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Serum amyloid A On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides


American Roentgen Ray Society Images of Serum amyloid A

All Images
Echo & Ultrasound
CT Images

Ongoing Trials at Clinical

US National Guidelines Clearinghouse

NICE Guidance

FDA on Serum amyloid A

CDC on Serum amyloid A

Serum amyloid A in the news

Blogs on Serum amyloid A

Directions to Hospitals Treating Psoriasis

Risk calculators and risk factors for Serum amyloid A