The ongoing quest for biomarkers in Ankylosing Spondylitis

Danve, Abhijeet; O'Dell, James Robert

doi:10.1111/1756-185x.12779

Cited by 36 publications

(20 citation statements)

References 82 publications

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“…Earlier diagnosis and treatment are urgently required and effective in reducing disease burden of AS patients while both of them are usually impeded due to the seronegative character and the absence of hallmark. Thus a number of emerging researches are focusing on the new biomarkers and antibodies, which can not only contribute to the diagnosis, but also reflect disease activity and curative effect [ 5 , 23 ], while the currently new biomarkers are still elusive due to the inconsistent results of different researches as well as lacking of multicenter studies. Therefore, only HLA-B27 and inflammatory marker CRP are widely accepted as routinely clinical biomarkers of AS.…”

Section: Discussionmentioning

confidence: 99%

Serum HMGB1 Serves as a Novel Laboratory Indicator Reflecting Disease Activity and Treatment Response in Ankylosing Spondylitis Patients

Wang

Miao

et al. 2016

Journal of Immunology Research

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Objective. High mobility group box 1 (HMGB1) is a late inflammatory factor participating in the pathogenesis of various autoimmune and inflammatory diseases. In the current study, we analyzed the association between serum levels of HMGB1 and clinical features of AS patients before and during treatment. Methods. Serum HMGB1 was detected in 147 AS patients and 61 healthy controls using ELISA. We evaluated the association between HMGB1 and extra-articular manifestations as well as disease severity indices. Among these AS patients, 41 patients received close follow-up at 1, 3, and 6 months after treatment. This group comprised 25 patients treated with anti-TNF-α biologics and 16 patients receiving oral NSAIDs plus sulfasalazine. Results. The serum HMGB1 of AS patients was significantly higher than in healthy controls and positively correlated with BASDAI, BASFI, ASDAS-ESR, ASDAS-CRP, ESR, and CRP, but not with HLA-B27, anterior uveitis, and recurrent diarrhea. There was no significant difference between patients with radiographic damage of hip joints and those without. We observed that serum HMGB1 paralleled disease activity after treatment. Conclusion. Serum level of HMGB1 is higher in AS patients, and to some extent, HMGB1 can reflect the activity of AS and be used as a laboratory indicator to reflect the therapeutic response.

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Section: Discussionmentioning

confidence: 99%

Serum HMGB1 Serves as a Novel Laboratory Indicator Reflecting Disease Activity and Treatment Response in Ankylosing Spondylitis Patients

Wang

Miao

et al. 2016

Journal of Immunology Research

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“…The availability and utility of serum and imaging biomarkers are limited in axSpA, especially compared with other rheumatic conditions (e.g., RA) [48,49]. Currently, HLA-B27 and C-reactive protein are the two most commonly used serum biomarkers, and MRI scans of the SIJs are the most sensitive imaging biomarker [50,51]. NHANES data indicate that 6.1% of the general US population is HLA-B27 positive [24], but a prevalence of 0.5% [52] for AS would account for only 8% of HLA-B27-positive individuals.…”

Section: Lack Of Reliable Biomarkersmentioning

confidence: 99%

Axial spondyloarthritis in the USA: diagnostic challenges and missed opportunities

Danve

Deodhar

2018

Clin Rheumatol

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Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease that primarily affects the sacroiliac joints and spine. Delayed or inadequate treatment may decrease quality of life and lead to poor long-term outcomes, including irreversible loss of spinal function. In this review, we discuss clinical practice related to axSpA within the USA, including prevalence, diagnosis, reasons for delayed/missed diagnosis, and suggestions for making early diagnosis. The US population prevalence of axSpA (0.9-1.4%) is higher than the diagnostic prevalence (0.2-0.7%). Although the estimated diagnostic delay for axSpA is 14 years in the USA, the disease can be identified earlier if appropriately preselected patients are quickly referred to rheumatologists. Only 37% of patients with ankylosing spondylitis in the USA are diagnosed by rheumatologists; the remaining 63% are diagnosed by primary care (26%), chiropractic/physical therapy (7%), orthopedic surgery (4%), pain clinics (4%), acute care (3%), and other settings (19%). To help reduce diagnostic delay, non-rheumatologist-healthcare professionals are urged to refer patients with back pain and ≥ 1 of 3 SpA features (HLA-B27 positivity, current inflammatory back pain, or x-ray/MRI evidence of sacroiliitis) to a rheumatologist. Prevalence and diagnosis rates of axSpA are disparate in the USA due to the lack of awareness and knowledge among non-rheumatologists. Progress has been made in identifying hurdles causing diagnostic delays. Public health initiatives are needed to guide primary care physicians, physical therapists, chiropractors, and other specialists seeing patients with chronic back pain on methods for suspecting or identifying axSpA and early referral to rheumatologists.Keywords Ankylosing spondylitis . Axial spondyloarthritis . Clinical practice in the USA . Inflammatory back pain . Non-radiographic axial spondyloarthritis . Referral strategy

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“…Osteoblasts stimulate osteoclastogenesis in a PDGFR-β-dependent manner (Bartelt et al, 2018), suggesting that PDGFR-β is related to bone development. Similar to matrix metalloproteinase-3 (MMP3), a useful serum marker of disease activity in AS patients (Danve and O'Dell, 2015), ADAMTS-10 is one of the primary enzymes that cleave collagen and proteoglycans. Both of them are involved in the process of disc degeneration, with MMP-3 up-regulated and ADAMTS-10 down-regulated in degenerative intervertebral disc tissue (Wang et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Circulating Retinol-Binding Protein 4 as a Possible Biomarker of Treatment Response for Ankylosing Spondylitis: An Array-Based Comparative Study

Chen

et al. 2020

Front. Pharmacol.

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Objective: To explore proteins associated with ankylosing spondylitis (AS) and to investigate potential proteins that may predict treatment response of adalimumab (ADA) in AS patients. Methods: In the discovery cohort, 39 AS patients and 20 healthy controls (HCs) were included, and 16 AS patients received ADA treatment for 24 weeks after included. In the validation cohort, 43 AS patients and 39 HCs were enrolled, and all 43 patients received ADA treatment after enrollment. Blood samples and clinical information were collected from two cohorts at baseline from all participants and week 24 from patients received ADA treatment. A human antibody array containing 1,000 proteins was used in the discovery phase, and Elisa kits were used for protein validation. Results: Compared with HCs, we identified 53 differentially expressed proteins (DEPs) in AS patients. Bioinformatics analysis revealed they were mostly enriched in coagulation function-related pathways, acute response signaling, and LXR/RXR activation. Bone metabolism pathways were also associated. Comparison between samples of pre-and post-ADA treatment revealed 42 DEPs. They were mostly associated with bone metabolism and inflammation response pathways. Significant enrichment was also found in LXR/RXR activation but not the coagulation functionrelated pathways. Upstream regulator analysis suggested that most regulators also significantly functioned under usage of ADA. Precisely, seven proteins were abnormally expressed in AS and restored after ADA treatment. Retinol-binding protein 4 (RBP4), one of the seven proteins, was validated that its baseline levels were inversely correlated with improvements in Ankylosing Spondylitis Disease Activity Score-C-reactive protein (ASDAS-CRP). Likewise, percentage changes in RBP4 levels were inversely correlated with changes in ASDAS-CRP score. Conclusion: A dysregulated serum protein profile existed in AS. ADA exerted a considerable but not entire alteration toward the dysregulation. RBP4 could be a biomarker for predicting and monitoring ADA treatment response.

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The ongoing quest for biomarkers in Ankylosing Spondylitis

Cited by 36 publications

References 82 publications

Serum HMGB1 Serves as a Novel Laboratory Indicator Reflecting Disease Activity and Treatment Response in Ankylosing Spondylitis Patients

Serum HMGB1 Serves as a Novel Laboratory Indicator Reflecting Disease Activity and Treatment Response in Ankylosing Spondylitis Patients

Axial spondyloarthritis in the USA: diagnostic challenges and missed opportunities

Circulating Retinol-Binding Protein 4 as a Possible Biomarker of Treatment Response for Ankylosing Spondylitis: An Array-Based Comparative Study

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