Hepatocyte growth factor is a potential biomarker for osteoproliferation and osteoporosis in ankylosing spondylitis

Torres, Luisa; Klingberg, Eva; Nurkkala, Merja; Carlsten, Hans; Forsblad-d’Elia, Helena

doi:10.1007/s00198-018-4721-4

Cited by 19 publications

(18 citation statements)

References 43 publications

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“…All other correlations tested between biomarkers in this panel and MRI inflammation in the spine yielded insignificant relationships. Two reports have recently described cross-sectional associations between hepatocyte growth factor (HGF) and acute phase reactants ( 17 , 18 ). HGF is secreted by mesenchymal cells and has pleiotropic effects that include suppression of inflammation and enhanced osteoblastic differentiation of mesenchymal cells.…”

Section: Disease Activity Biomarkersmentioning

confidence: 99%

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

Maksymowych

2019

Front. Immunol.

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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.

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Section: Disease Activity Biomarkersmentioning

confidence: 99%

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

Maksymowych

2019

Front. Immunol.

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“…Also, an increased average s-HGF was associated with development of new syndesmophytes in men. s-HGF in relation to AS-related spinal alterations has, to our knowledge, only been evaluated before in our baseline, cross-sectional study, which demonstrated that higher s-HGF was associated with higher mSASSS [ 15 ]. The pathophysiological mechanisms behind the relationship between new bone formation and HGF in AS are not known, but there are several possibilities.…”

Section: Discussionmentioning

confidence: 99%

“…Previously, we have shown that serum HGF (s-HGF) was higher in patients with AS than in controls and independently associated with higher modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) [ 15 ]. The aims of the present study were to assess (i) baseline s-HGF as a predictor for spinal radiographic progression over 5 years overall and by sex, and (ii) if demographic characteristics, disease activity and medications are correlated with changes in s-HGF.…”

Section: Introductionmentioning

confidence: 99%

Elevated serum level of hepatocyte growth factor predicts development of new syndesmophytes in men with ankylosing spondylitis

et al. 2020

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Objectives To study baseline serum hepatocyte growth factor (s-HGF) as a predictor of spinal radiographic progression overall and by sex and to analyse factors correlated to changes in s-HGF in patients with AS. Methods At baseline and the 5-year follow-up, s-HGF was analysed with ELISA. Spinal radiographs were graded according to modified Stoke Ankylosing Spondylitis Spinal Score. Radiographic progression was defined as ≥2 modified Stoke Ankylosing Spondylitis Spinal Score units/5 years or development of ≥1 syndesmophyte. Logistic regression analyses were used. Results Of 204 baseline participants, 163 (80%) completed all examinations at the 5-year follow-up (54% men). Baseline s-HGF was significantly higher in men who developed ≥1 syndesmophyte compared with non-progressors, median (interquartile range) baseline s-HGF 1551 (1449–1898) vs 1436 (1200–1569) pg/ml, P = 0.003. The calculated optimal cut-off point for baseline s-HGF ≥1520 pg/ml showed a sensitivity of 70%, a specificity of 69% and univariate odds radio (95% CI) of 5.25 (1.69, 14.10) as predictor of development of ≥1 new syndesmophyte in men. Baseline s-HGF ≥1520 pg/ml remained significantly associated with development of ≥1 new syndesmophyte in men in an analysis adjusted for the baseline variables age, smoking, presence of syndesmophytes and CRP, odds radio 3.97 (1.36, 11.60). In women, no association with HGF and radiographic progression was found. Changes in s-HGF were positively correlated with changes in ESR and CRP. Conclusion In this prospective cohort study elevated s-HGF was shown to be associated with development of new syndesmophytes in men with AS.

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“…The role of HGF was also proven in the progression of AS. L. Torres et al [ 247 ] demonstrated higher levels of HGF in the serum of AS patients compared to healthy donors, which directly correlated with the disease activity and inversely correlated with the level of BMD. This observation demonstrates the importance of this cytokine in diagnostics and treatment of AS and osteoporosis as a frequent AS complication.…”

Section: Aptamers For Protein Biomarkers Of Rheumatic Disordersmentioning

confidence: 99%

Aptamers for Proteins Associated with Rheumatic Diseases: Progress, Challenges, and Prospects of Diagnostic and Therapeutic Applications

et al. 2020

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Nucleic acid aptamers capable of affine and specific binding to their molecular targets have now established themselves as a very promising alternative to monoclonal antibodies for diagnostic and therapeutic applications. Although the main focus in aptamers’ research and development for biomedicine is made on cardiovascular, infectious, and malignant diseases, the use of aptamers as therapeutic or diagnostic tools in the context of rheumatic diseases is no less important. In this review, we consider the main features of aptamers that make them valuable molecular tools for rheumatologists, and summarize the studies on the selection and application of aptamers for protein biomarkers associated with rheumatic diseases. We discuss the progress in the development of aptamer-based diagnostic assays and targeted therapeutics for rheumatic disorders, future prospects in the field, and issues that have yet to be addressed.

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Hepatocyte growth factor is a potential biomarker for osteoproliferation and osteoporosis in ankylosing spondylitis

Cited by 19 publications

References 43 publications

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

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

Elevated serum level of hepatocyte growth factor predicts development of new syndesmophytes in men with ankylosing spondylitis

Aptamers for Proteins Associated with Rheumatic Diseases: Progress, Challenges, and Prospects of Diagnostic and Therapeutic Applications

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