Review Article

Biomarkers in Inflammatory Bowel Disease-Associated Spondyloarthritis: State of the Art and Unmet Needs

Table 1

Properties of candidate biochemical markers for inflammatory bowel disease-associated spondyloarthritis.

ReferenceCandidate biomarkerSamplingPopulationFindingsNotes

Hoffman et al. [41]ASCA (IgA and/or IgG)Serum26 patients with CD, 108 patients with SpA, 56 patients with RA, and 45 healthy controlsASCA IgA levels similar between patients with SpA with and without histologically proved gut inflammationASCA IgA levels were raised in AS and uSpA vs. RA and HC (AUC 0.72)

Bernardi et al. [80]YKL-40Serum171 patients: 29 PsA, 66 IBD (36 CD and 30 UC), and 76 SpA/IBD (44 CD/32 UC)YKL-40 levels significantly higher in SpA/IBD vs. IBD patients (AUC 0.82)

De Vries et al. [48]pANCASerum179 patients: 52 with AS, 50 with UC, 51 with CD, and 26 with IBD+ASpANCA associated with UC in AS patients (OR 8.2, 95% CI 1.2–55.6)pANCA detected in 21% of AS patients
ASCA (IgA and/or IgG)Serum179 patients: 52 with AS, 50 with UC, 51 with CD, and 26 with IBD+ASASCA found in 40% of SpA/CD vs. 30% of AS and 90% of CD patientsNot useful
OmpC antibodiesSerum179 patients: 52 with AS, 50 with UC, 51 with CD, and 26 with IBD+ASOmpC Ab found in 30% of SpA/IBD patients and 19% of AS patientsNot useful

Al-Jarallah et al. [81]Anti-MCVSerum125 IBD patients (44 of which with SpA/IBD) vs. 81 healthy controlsAnti-MCV positivity similar between IBD and HC (16.8% vs. 16.0%)
No discrimination between SpA/IBD and IBD
Not useful
Anti-CCP2Serum125 IBD patients (44 of which with SpA/IBD) vs. 81 healthy controlsAnti-CCP2 positivity similar between IBD and HC (6.4% vs. 6.2%)
No discrimination between SpA/IBD and IBD
Not useful

Wallis et al. [49]ASCA IgG and IgASerum76 patients with AS, 77 patients with AS/IBD, and 48 patients with mechanical back painASCA IgG higher in AS/IBD than AS patients (14% vs. 0%)
Anti-OmpCSerum76 patients with AS, 77 patients with AS/IBD, and 48 patients with mechanical back painAnti-OmpC higher in AS/IBD than AS patients (27% vs. 12%)
Anti-CBir1Serum76 patients with AS, 77 patients with AS/IBD, and 48 patients with mechanical back painAnti-CBir1 higher in AS/IBD than AS patients (42% vs. 20%)
ANCASerum76 patients with AS, 77 patients with AS/IBD, and 48 patients with mechanical back painANCA not significantly different between AS/IBD and AS patientsNot useful

Klingberg et al. [55]CalprotectinFeces164 AS patients followed up for 5 yearsThe development of CD (3 pts) predicted by (AUC 0.91)
No incident cases of UC in the AS population
Fecal calprotectin was elevated (>50 mg/kg) in 70% pts at the baseline
Globally, 7.4% of patients had signs of inflammation in the large or small intestine

Viladomiu et al. [88]IgA-coated E. coliFecal microbiome59 IBD patients with or without peripheral SpAIgA-coated E. coli enriched in CD-SpA vs. CD aloneCD-SpA E. coli isolates induced Th17 mucosal immunity

Luchetti et al. [74]SOSTSerum85 pts with axial or peripheral SpA/IBD
Control groups (IBD, AS, RA, and HC)
Lower levels in AxSpA/IBD vs. PerSpA/IBD and control groups (AUC 0.88)Lower levels of SOST correlate with higher levels of anti-SOST-Ig
Anti-SOST antibodiesSerum85 pts with axial or peripheral SpA/IBD
Control groups (IBD, AS, RA, and HC)
Higher levels in AxSpA/IBD vs. PerSpA/IBD and control groups (AUC 0.84)Higher levels of anti-SOST-Ig correlate with lower levels of SOST