Biomarkers for Diagnosis of Axial Spondyloarthritis, Disease Activity, Prognosis, and Prediction of Response to Therapy

Abstract

There exists a major unmet need for biomarkers that can identify axial spondyloarthritis (axSpA) early after disease onset because of the availability of highly effective therapies. Several recent reports have examined the autoantibody response in patients with axSpA through the use of protein microarrays and protein-protein interactions although diagnostic performance of biomarkers identified to date has been inadequate. An example of such a biomarker is protein phosphatase magnesium-dependent 1A. Antibodies to the human leukocyte antigen class II-associated invariant chain peptide (anti-CD74) are candidate diagnostic biomarkers but sensitivity declines with increasing duration of disease. Metabolomic studies have employed nuclear magnetic resonance (NMR) spectrometry to identify disease-specific metabolites related to fat metabolism and intestinal microbial metabolism. A second major unmet need exists for biomarkers of disease activity that have superiority over standard C-reactive protein assessment and reflect MRI inflammation in the axial spine. Several biomarkers reflecting inflammation (calprotectin), angiogenesis (vasoactive endothelial growth factor), and connective tissue turnover (C2M, C3M, and citrullinated metalloproteinase degraded fragment of vimentin) have recently been shown to reflect disease activity when compared with clinical outcomes but comparisons with MRI inflammation are very limited. With increasing availability of highly effective but costly therapies, a third unmet need is biomarkers that can predict response to therapies with different mechanisms of action and are superior to C-reactive protein. Calprotectin is currently the only candidate. Although there are as yet no proven therapies for preventing progression of disease there is an unmet need for biomarkers of prognosis that are more responsive than radiography. Aside from CRP no consistent candidates have emerged. Future studies will need to be prospective, include consecutive patients presenting with undiagnosed back pain, and use more reliable and objective endpoints such as MRI inflammation. Moreover, it has become evident that targeted biomarker studies have not been successful in identifying clinically useful biomarkers and technologies that can simultaneously assess “multiomic” markers will need to be analyzed for future advances. These include more sophisticated metabolomic profiling and universal metabolome-standard (UMS) methodology, next generation RNA sequencing, and affinity-based quantitative proteomics based on the use of nucleic acid binders such as the aptamer-based SOMAscan assay.

Multi-omics Analysis at Serum Proteomic and Metabolomic Levels Reveals Mechanisms of Moxibustion for a Mouse Model of Ankylosing Spondylitis

“…Both of them play a prominent role in the metabolism of energy. It had been well reported that metabolites and proteins involved in the TCA cycle were signi cantly raised to enhance energy production, so as to compensate for insu cient energy sources caused by glycolysis under AS in ammation condition [70]. Similarity, in this study, the levels of citric acid and VCP increased in the PG-induced AS model mice group compared with the healthy control group, suggesting a boosted energy supply to compensate for the shortage of body energy.…”

“…Some speci c gut pathogens, including the Helicobacter pylori, have been proven to trigger the release of MIF [93]. Subsequently, the production of MIF from the gut may drive the new bone formation in patients with AS via activating and mineralizing OBs, upregulating genes involved in osteogenesis, and triggering the stabilization of β-catenin, an important mediator involved in the OBspeci c Wnt/β-catenin pathway [70]. Thus, it is not surprising to detect the high concentration of MIF in patients with AS [94].…”

Metabolites of type I, II, III, and IV collagen may serve as markers of disease activity in axial spondyloarthritis

“…Inflammation is currently assessed by C-reactive protein (CRP), which is elevated in AS patients compared to nr-axSpA patients 8,12,13 . An increase in CRP may arise from many pathological events, such as a common cold or chronic inflammation.…”

The semi-automated algorithm for the detection of bone marrow oedema lesions in patients with axial spondyloarthritis

“…Axial spondyloarthritis (axSpA) is an inflammatory rheumatic condition, involving primarily an axial skeleton and progressively leading to the sacroiliac, intervertebral and facet joint immobilization [1]. The definition of active sacroiliitis in MRI, fulfilling the ASAS (Assessment in SpondyloArthritis international Society) criteria, is bone marrow oedema visible on T2-weighted sequence sensitive for free water (e.g., STIR sequence) or bone marrow enhancement (osteitis) present on T1-weighted sequence after contrast media administration.…”