Intest Res.  2022 Apr;20(2):203-212. 10.5217/ir.2021.00020.

Fecal S100A12 is associated with future hospitalization and step-up of medical treatment in patients with Crohn’s disease in clinical remission: a pilot study

• Lee SH
• Hwang SW
• Park SH
• Yang DH
• Byeon JS
• Myung SJ
• Yang SK
• Ye BD

• KMID: 2529566
• DOI: http://doi.org/10.5217/ir.2021.00020

Abstract

Background/Aims
Fecal S100A12 (FS) and serum S100A12 (SS) have been reported as novel biomarkers that accurately reflect intestinal inflammation. We evaluated if FS and SS in comparison to fecal calprotectin (FC) are associated with poor future outcomes in clinically quiescent Crohn’s disease (CD) patients.
Methods
We prospectively enrolled 49 CD patients in clinical remission (Crohn’s Disease Activity Index [CDAI] < 150 for the past 6 months). Patients were followed for a median period of 4.4 years (interquartile range [IQR], 4.3–4.5). The following outcomes were evaluated: clinical relapse, CD-related hospitalization, step-up of medical treatment, and CD-related intestinal resection. Cox proportional-hazard regression model was constructed to assess the association of baseline markers with time-to-event outcomes.
Results
The median levels of baseline FS, FC, and SS were 0.042 mg/kg (IQR, 0.005–0.179), 486.8 mg/kg (IQR, 203.5–886.8) and 1,398.2 ng/mL (IQR, 791.8–2,759.9), respectively. FS correlated with FC (r = 0.689), erythrocyte sedimentation rate (r = 0.524), C-reactive protein (r = 0.499), and albumin (r = –0.446), but not with CDAI (r = 0.045). Interestingly, increased FS (top quartile) was associated with a 4.9-fold increased rate of future CD-related hospitalization (P= 0.009) and a 2.8-fold increased rate of step-up of medical treatment (P= 0.032), whereas increased FC and SS were not. These findings remained significant after adjusting for age, sex, disease duration, current smoking, C-reactive protein, serum albumin, CDAI, and FC, individually.
Conclusions
In this pilot study, increased FS and not FC or SS, was significantly associated with increased rates of future CD-related hospitalization and step-up of medical treatment among CD patients in clinical remission.

Keyword

S100A12 protein; Calprotectin; Crohn disease

Figure

• 

  Fig. 1. Spearman correlation between baseline fecal markers, serum markers, and disease activity score. FS, fecal S100A12; FC, fecal calprotectin; SS, serum S100A12; WBC, white blood cell count; Hb, hemoglobin; Hct, hematocrit; Plt, platelet count; Alb, albumin; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein.

• 

  Fig. 2. Association of baseline fecal S100A12 (FS) with time to future outcomes after adjusting for co-variables. The effect size of FS (odds ratio and 95% confidence interval) on clinical outcomes are plotted. Each continuous variable was dichotomized into the top quartile versus the others. CD, Crohn’s disease; CRP, C-reactive protein; CDAI, Crohn’s Disease Activity Index.

• 

  Fig. 3. Comparison of top quartile (red line) versus bottom 3 quartiles (blue line) of fecal S100A12 for its association with the cumulative event-free survival of the following outcomes: (A) time to clinical relapse; (B) time to Crohn’s disease (CD)-related hospitalization; (C) time to step-up of medical treatment; (D) time to CD-related intestinal resection. Top quartile: fecal S100A12 ≥0.179 mg/kg. HR, hazard ratio; CI, confidence interval.

• 

  Fig. 4. Comparison of fecal S100A12 ≥optimal cutoff (red line) versus fecal S100A12 optimal cutoff (blue line) for its association with the cumulative event-free survival of the following outcomes: (A) time to clinical relapse; (B) time to Crohn’s disease (CD)-related hospitalization; (C) time to step-up of medical treatment; (D) time to CD-related intestinal resection. Optimal cutoff value: 0.0136 mg/kg for time to clinical relapse; 0.1994 mg/kg for time to CD-related hospitalization and step-up of medication; 0.1596 mg/kg for time to CD-related intestinal resection. HR, hazard ratio; CI, confidence interval.

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