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Serum amyloid A

ISSN 2398-2977

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Synonym(s): SAA

Podcast: Serum amyloid A

Introduction

  • Serum amyloid A is a major equine acute phase protein.
  • It is a highly sensitive, rapidly reacting inflammatory protein which has very low or undetectable levels in the plasma of healthy individuals and very high levels in plasma of individuals suffering from septic and aseptic inflammatory disease.
  • It is produced by hepatocytes and certain non-hepatic cell types under the influence of cytokines.
  • Cytokines are released from cells, especially monocytes and macrophages, activated by aseptic and septic stimuli during the acute phase response.
  • SAA is complexed to high density lipoprotein in plasma.
  • Synthesis rate is the only important determinant of the plasma concentration.
  • SAA has a short half-life and SAA concentrations start to decline shortly after synthesis has ceased.

Normal ranges

  • Most normal horses have immeasurable levels, quoted normal ranges obtained with different assays are <20 mg/l.
  • Levels may be slightly higher than basal in neonatal foals (up to 200 mg/l) and in post-parturient mares.
  • Otherwise, no consistent age or gender variation has been demonstrated.

Pathological changes

  • In the face of acute, particularly septic inflammation, levels increase quickly (within 24 h) to over 20 mg/l and often >100 mg/l (peak 2-3 days). Levels up to more than 2000 mg/l have been demonstrated in horses with bacterial infections.
  • There is an extended dynamic range (up to several 1000 fold increase).
  • Levels return to baseline within 7-10 days of resolution of the acute inflammatory insult.

Uses

  • SAA can be used together with other hematological and blood biochemical markers for assessment of inflammatory conditions.
  • SAA detects acute phase response to all harmful stimuli causing inflammation (infective, inflammatory, traumatic, toxic and neoplastic insults.
  • Particularly high levels are seen in the acute or active phase of bacterial infections and there is rapid fall-off with effective antimicrobial therapy.
  • Elevated plasma SAA levels have been reported in horses suffering from diarrhea   Diarrhea: parasitic    Diarrhea: antimicrobial associated  , infectious and non-infectious arthritis   Joint: septic arthritis - adult  , strangles   Strangles (Streptococcus equi infection)  , pneumonia   Lung: pleuropneumonia - bacterial (pleuritis)  , sepsis and colic   Abdomen: pain - adult  . Elevated levels have been reported in virus infections, including equine Herpesvirus   Equine herpesvirus  and equine influenza virus infection   Equine influenza  .
  • SAA seems to be particularly useful for differentiating infectious from non-infectious causes of weakness in neonatal foals. Repeated blood sampling may be necessary in the patient to determine whether slightly elevated SAA levels are those expected in the neonatal foal due to the birth process (levels will fall), or whether they are the result of infection/sepsis developing in the patient (levels will increase).
  • SAA can be used for monitoring occurrence of post-operative complications such as infection. The normal post-operative SAA response has a rise-and-fall pattern (levels return to pre-operative values within 5-10 days, depending on size of the surgical trauma); infectious complications should be suspected when levels remain elevated for an extended period of time post-operatively.
  • SAA levels change parallel to changes in activity of inflammatory disease, as may occur after successful treatment or exacerbation/relapse of disease. SAA is therefore highly suited for real-time monitoring of inflammatory activity, eg in infectious diseases after treatment with antimicrobials.
  • SAA may be used to monitor spread of infections through groups of horses, as SAA levels remained undetectable in horses that, despite being in contact with infections such as herpes virus or strangles, did not contract the disease.
  • Recent studies have shown that SAA can be measured not only in equine serum and plasma, but also in synovial fluid and colostrum/early milk. Horses with septic arthritis   Joint: septic arthritis - adult  have high SAA concentrations in serum and in synovial fluid.

Limitations

  • It is important to remember that cytokines responsible for hepatic acute phase protein synthesis are released from inflamed or injured tissue independent of the cause of tissue injury, and that acute phase proteins, such as SAA, as a consequence are non-specific markers of inflammation and cannot be used for making etiological diagnoses.

Test methodology

  • Several methods for measuring SAA have been developed.
  • The automated latex immunoturbidometric method (EIKEN LZ-serum amyloid A assay, Mastgroup, Merseyside, UK) is particularly well suited for routine diagnostic procedures and based on this assay, SAA analyses are now available at a number of veterinary diagnostic laboratories.
  • Recently, a test system (Equinostic, Copenhagen, Denmark -  www.equinostic.com ) developed for use in equine practice and small diagnostic labs, has been marketed in the UK and Scandinavia. The SAA assay included in this test system was recently validated and found sufficiently accurate and precise for use in equine practice.
  • Other methods such as latex agglutination nephelometric immunoassay, radial immunodiffusion, ELISA assay have been less well validated or are more suitable for research purposes.
  • As with all laboratory tests, SAA concentrations measured by different assay methodologies are not directly comparable.

Sample

  • Serum or plasma, volume depends on assay system used, but often small (0.5 ml or less).
  • Sample obtained by standard venipuncture.
  • Sample must be analyzed within 24 h, preferably less. Extended storage may give falsely low concentrations.

Validity

  • Sensitivity - for detection of inflammation: high.
  • Specificity - for ruling out inflammation: high.
  • SAA cannot be used for marking etiological diagnoses, but is very useful for ruling in/out presence of inflammation.

Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Labelle A L et al (2011) Effects of ophthalmic disease on concentrations of plasma fibrinogen and serum amyloid A in the horse. Equine Vet J 43 (4), 460-465 PubMed.
  • Jacobsen S & Kjelgaard-Hansen M (2008) Evaluation of a commercially available apparatus for measuring the acute phase protein serum amyloid A in horses. Vet Rec 163 (11), 327-330 PubMed.
  • Duggan V (2008) Serum amyloid A in the neonatal foal: the significance of peri-parturient events. Vet J 176 (3), 267-269 PubMed.
  • Jacobsen S & Andersen P H (2007) The acute phase protein serum amyloid A (SAA) as a marker of inflammation in horses. Equine Vet Educ 19 (1), 38-46.
  • Jacobsen S, Halling-Thomsen M & Nanni S (2006) Concentrations of serum amyloid A in serum and synovial fluid from healthy horses and horses with joint disease. Am J Vet Res 67, 1738-1742 PubMed.
  • Jacobsen S, Jensen J C, Frei S, Jensen A L & Thoefner M B (2005) Use of serum amyloid A and other acute phase reactants to monitor the inflammatory response after castration in horses: a field study. Equine Vet J 37, 552-556 PubMed.
  • Hulten C & Demmers S (2002) Serum amyloid A (SAA) as an aid in the management of infectious disease in the foal: comparison with total leucocyte count, neutrophil count and fibrinogen. Equine Vet J 34, 693-698 PubMed.
  • Stoneham S J, Palmer L, Cash R & Rossdale P D (2001) Measurement of serum amyloid A in the neonatal foal using a latex agglutination immunoturbidometric assay: determination of the normal range, variation with age and response to disease. Equine Vet J 33, 599-603 PubMed.
  • Hultén C, Sandgren B, Skioldebrand E et al (1999) The acute phase protein serum amyloid A (SAA) as an inflammatory marker in equine influenza virus infection. Acta Vet Scand 40, 323-333 PubMed.
  • Wada A, Yamada T & Kuboto N (1997) Measurement of serum amyloid A by commonly used automated analysers. Ann Clin Biochem 34, 569-574 PubMed.
  • Nunokawa Y, Fujinaga T, Taira T et al (1993) Evaluation of serum amyloid A protein as an acute-phase reactive protein in horses. J Vet Med Sci 55, 1011-1016 PubMed.
  • Chavatte P M, Pepys M B,  Roberts B et al (1992) Measurement of serum amyloid A protein (SAA) as an aid to differential diagnosis of infection in newborn foals. Equine Inf Dis VI, 33-38.
  • Pepys M B, Bajtz M I, Tennant G A et al (1989) Serum amyloid A protein (SAA) in horses; objective measurement of the acute phase response. Equine Vet J 21, 106-109 PubMed.