Overview of biomarkers and their relationship to axial spondyloarthritis associated with idiopathic inflammatory bowel diseases
Abstract
Axial spondyloarthritis (spondyloarthropathies or spondyloarthritides - axSpA) accompanied by idiopathic bowel disease (IBD), also known as enteropathic spondyloarthritis, are systemic diseases characterized by chronic inflammation of both the musculoskeletal and gastrointestinal tracts. The incidence of IBD in patients with spondylarthritis (SpA) has been reported in 6-14%, but almost 60% of patients with SpA have subclinical macroscopic or microscopic inflammatory bowel disease on endoscopic examination.
The presence of the human leukocyte antigen 27 (HLA-B27) gene in SpA/IBD is around 50-80%. This is significantly less than in ankylosing spondylitis (AS), where about 85-95% of patients are HLA-B27 positive.
To date, there are few markers that can predict the development of IBD in axSpA. Endoplasmic reticulum aminopeptidase (ERAP-1) appears to be a promising indicator.
ERAP-1 is also considered as one of the possible pathophysiological factors that contribute to the development of ulcerative colitis (UC) in patients with axSpA. Other gene variants related to the IL-17/23 pathway have been described.
In IBD, a NOD2/CARD15 polymorphism appears to be the candidate gene. The presence of at least one of the three known gene variants of NOD2/CARD15 increases the risk of developing IBD, especially Crohn's disease (CD), and is also associated with the risk of developing sacroiliitis in patients with IBD.
Unlike HLA-B27, NOD2/CARD15 is not associated with a risk of developing SpA in patients with IBD. Disease-specific shared genes such as IL23R, IL12B, STAT3, PTGER4, and others have also been described.
Acute phase reactants (CRP, ESR), composite indices (BASDAI, ASDAS score), a group of cytokines (IL-2, IL-6, IL-11, IL-23), pANCA antibodies, ASCA antibodies, and serum and faecal calprotectin are used to diagnose or evaluate disease activity. Predictors of radiographic progression in axSpA include, e.g., the determination of DKK-1, sclerostin and antisclerostin.
In this work, we present an overview of the most promising biomarkers to date and their relationship to axial spondylarthritis associated with IBD. Finding suitable biomarkers could shed light not only on the pathogenesis of the disease but also on the possibility of correlating the mutual activity of axSpA and IBD.