SAA as a biomarker of IBD

Inflammatory bowel disease (IBD) needs long-term management through assessing and monitoring disease activity, however, frequent examination via colonoscopy could cause high burden both physically and costly on patients. The patients are often children and young people. Recently, non- or less- invasive methods might have been widely used for monitoring disease activity of IBD: fecal calprotectin and C-reactive protein (CRP) in blood test.

Fecal calprotectin has been used as a non-invasive test whose levels highly correlate with endoscopic indices of disease activity [*1]. However, it might be difficult for patients to have bowel movement and get the result at a hospital on the same day of periodic checkup.

CRP is measured as a less invasive blood test that can reflect the level of mucosal inflammation levels. On the other hand, it has low sensitivity to predict active disease in ulcerative colitis (UC), whereas fecal calprotectin is the more accurate marker which correlate greatly with endoscopic inflammation in UC [*1].

Serum amyloid A (SAA), the same as CRP, is one of the acute phase proteins (APP) synthesized in the liver and exists in blood. Some research indicate SAA is a more sensitive serum biomarker in monitoring the disease activity of UC and Crohn’s disease [*2, 3].

• In ulcerative colitis patients:
• Wakai et al. (2020) compared CRP and SAA levels of UC patients in clinical remission, which indicates that SAA has strong correlation with mucosal condition assessed by Mayo Endoscopic Score (MES) [*4]. In MES 2 or 3 (non-mucosal healing) patients, the area under the ROC curve of SAA and CRP were reported as 0.807 and 0.701, respectively.
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• In Crohn’s disease (CD) patients:
• Ishihara et al. (2018) mentioned that there was a significant correlation of SAA with endoscopic disease activity in patients with CD [*5]. Yarur et al. (2017) showed that SAA had higher sensitivity and specificity than CRP for predicting mucosal inflammation, moreover, SAA levels were higher in 70% of patients with normal CRP levels but with active inflammation [*6].
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As described above, there are several studies that anticipate the potential of SAA for predicting mucosal healing of IBD. SAA can be measured quickly with a clinical chemistry analyzer like CRP. If further research is conducted, the utility value of SAA may expand in the future, and it might be one of the options that can reduce the burden on IBD patients.

Penna et al. (2021) mentioned that “the sequential usage of fecal calprotectin and CRP showed greater specificity (82%) when compared to the use of these markers alone. ... Fecal calprotectin and CRP tests are useful to differentiate patients in remission from those in activity, because these tests presented good accuracy in the diagnosis of inflammatory activity in CD.” [*7] In addition, the study suggests the algorism that the combined or consecutively fecal calprotectin and CRP are performed, will allow to make a decision with a great degree of certainty and reduce the number of unnecessary colonoscopies.

In our publication searches, we could not find results in the sequential usage of fecal calprotectin with SAA.

*LZ-SAA ‘Eiken’ is currently for research use only. OC-FCa™ Reagent is for in vitro diagnostics.

1. Maaser C, Sturm A, Vavricka SR, et al. ECCO-ESGAR Guideline for Diagnostic Assessment in IBD Part 1: Initial diagnosis, monitoring of known IBD, detection of complications. Journal of Crohn's and Colitis, Volume 13, Issue 2, February 2019, Pages 144–164K.
2. Chambers RE, Stross P, Barry RE, Whicher JT. Serum amyloid a protein compared with C-reactive protein, alpha 1-antichymotrypsin and alpha 1- acid glycoprotein as a monitor of inflammatory bowel disease. Eur J Clin Investig. 1987;17:460–7.
3. Niederau C, Backmerhoff F, Schumacher B, Niederau C. Inflammatory mediators and acute phase proteins in patients with Crohn’s disease and ulcerative colitis. Hepatogastroenterology. 1997;44:90–107.
4. Wakai M, Hayashi R, Tanaka S, et al. Serum amyloid A is a better predictive biomarker of mucosal healing than C-reactive protein in ulcerative colitis in clinical remission. BMC Gastroenterol 20, 85 (2020).
5. Ishihara S, Tada Y, Kawashima K, et al. Serum amyloid A level correlated with endoscopic findings in patients with Crohn's disease-Possible biomarker for evaluating mucosal healing. Dig Liver Dis. 2018 Jun;50(6):553-558. 
6. Yarur AJ, Quintero MA, Jain A, et al. Serum Amyloid A as a Surrogate Marker for Mucosal and Histologic Inflammation in Patients with Crohn's Disease. Inflamm Bowel Dis. 2017 Jan;23(1):158-164.
7. Penna FGC, Rosa RM, Pereira FH, et al. Combined evaluation of fecal calprotectin and C-reactive protein as a therapeutic target in the management of patients with Crohn's disease. Gastroenterol Hepatol. 2021 Feb;44(2):87-95. English, Spanish.