Encyclopedia
Please note this is an old version of this entry, which may differ significantly from the current revision.
Subjects:
Rheumatology
Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that can lead to ankylosis by secondary ossification of inflammatory lesions, with progressive disability and a significant impact on quality of life. It is also a risk factor for the occurrence of comorbidities, especially cardiovascular diseases (CVDs), mood disorders, osteoporosis, and malignancies. Early diagnosis and treatment are needed to prevent or decrease functional decline and to improve the patient’s prognosis. In respect of axSpA, there is an unmet need for biomarkers that can help to diagnose the disease, define disease activity and prognosis, and establish personalized treatment approaches. The aim of this review was to summarize the available information regarding the most promising biomarkers for axSpA. We classified and identified six core categories of biomarkers: (i) systemic markers of inflammation; (ii) molecules involved in bone homeostasis; (iii) HLA-B27 and newer genetic biomarkers; (iv) antibody-based biomarkers; (v) microbiome biomarkers; and (vi) miscellaneous biomarkers. Unfortunately, despite efforts to validate new biomarkers, few of them are used in clinical practice; however, we believe that these studies provide useful data that could aid in better disease management.
- axial spondyloarthritis
- diagnosis
- disease activity
- prognosis
1. Axial Spondyloarthritis: Past, Present, and Future
Spondyloarthritis (SpA) comprises a group of chronic immune-mediated inflammatory conditions with overlapping clinical and genetic features but with substantial heterogeneity, as inflammation can affect peripheral and axial joints and also result in extraarticular manifestations (enthesitis, dactylitis, uveitis, inflammatory bowel disease, psoriasis) [1,2,3].
SpA comprises a spectrum of diseases with significant overlaps between SpA phenotypes, which can be classified according to the Assessment of Spondyloarthritis International Society (ASAS) 2009 classification criteria. These depend on where patients primarily experience symptoms in axial SpA (axSpA) with predominantly axial manifestations, including non-radiographic (nr-axSpA) and radiographic axSpA (r-axSpA) or ankylosing spondylitis (AS) and peripheral SpA (pSpA) with predominant peripheral involvement (psoriatic arthritis, reactive arthritis, enteropathic arthritis, juvenile-onset SpA, and undifferentiated SpA) [4]. While the spectrum of axSpA extends from early or mild disease through severe or late disease with erosive damage in the sacroiliac joints, this arbitrary division of nr-axSpA and r-axSpA is becoming less clinically relevant.
The symptoms of axSpA create a significant burden for both patients and society. The major disease feature is the progression to ankylosis by secondary ossification of inflammatory lesions, with progressive disability and a significant impact on quality of life.
AxSpA is also a risk factor for the occurrence of comorbidities, especially cardiovascular diseases (CVDs), mood disorders, osteoporosis, and malignancies, which shows that axSpA has a systemic character and influences patient health in a complex manner [2]. All these characteristics affect quality of life and, because all comorbidity types correlate with axSpA, early diagnosis and treatment are needed to prevent or decrease functional decline and improve the patient’s prognosis.
2. AxSpA and Biomarkers
According to the World Health Organization, a biomarker is a chemical, physical, or biological indicator of disease presence, activity, or severity, which can provide vital information. In respect of axSpA, there is an unmet need for biomarkers that can help to diagnose the disease, define disease activity and prognosis, and establish personalized treatment approaches [5].
Despite the progress made in the concept of axSpA, its identification remains challenging, frequently resulting in a diagnostic delay for patients. Ideally, the diagnosis should be made before the development of radiographic sacroiliitis, but currently the most sensitive imaging diagnosis method is magnetic resonance imaging (MRI), which is costly and not widely available [2].
AxSpA disease activity is monitored using the following scores: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Ankylosing Spondylitis Disease Activity Score (ASDAS), which may be subjective. Disease activity is also monitored by measuring of one of the most common inflammatory biomarkers, C-reactive protein (CRP), which is insensitive for this disease [6].
Although the range of effective modern drugs for axSpA has expanded in recent decades, therapeutic decisions and the response to specific therapies remain challenges in current practice, and further research is therefore required. Adequate evaluation of disease activity, radiographic progression, response to treatment and identification of negative prognostic factors can improve the therapeutic decision. In addition, data regarding the axSpA prognosis obtained in the early disease stages will improve therapeutic management [2].
The aim of was to summarize available information regarding the most promising biomarkers for axSpA. The researchers further refer to six core categories of biomarkers: (i) systemic markers of inflammation; (ii) molecules involved in bone homeostasis; (iii) HLA-B27 and newer genetic biomarkers; (iv) antibody-based biomarkers; (v) microbiome biomarkers; and (vi) miscellaneous biomarkers (Table 1, Figure 1). Furthermore, the association between biomarkers and diagnosis, disease activity, structural damage, and treatment response are described below.
Figure 1. Biomarkers significance in axial spondiloarthtitis.
Table 1. Biomarkers significance in axial spondyloarthritis.
| Biomarker | Predictability | Study type | Reference |
|---|---|---|---|
| Anti-CD74 antibodies | Positive association with diagnosis and disease activity. Positive association with radiographic progression. Positive association with diagnosis. Negative association with diagnosis. Positive association with diagnosis. |
Cross-sectional study Prospective study Prospective study Prospective study Prospective study |
2021, Marwa Mahmoud Abdelaziz [7] 2021, Lan Do [8] 2019, Nelly R. Ziade [9] 2018, Janneke J. de Winter [10] 2020, Chao-Jun Hu [11] |
| Bone morphogenetic protein 7 (BMP-7), sclerostin, dicckopf-1 (DKK-1) | Positive association with disease association |
Prospective multicenter study | 2021, Elise Descamps [12] |
| C-reactive protein (CRP) | Positive association with cardiovascular risk Positive association with treatment response Positive association with treatment response Positive association with treatment response |
Retrospective analysis Prospective study Case-control study Cross-sectional study |
2022, Luca Navarini [13] 2019, Xenofon Baraliakos [14] 2020, Xu Yuansheng [15] 2018, Björn Sundström [16] |
| C-C motif chemokine ligand 11 (CCL11) | Positive association with radiographic progression |
Cross-sectional study | 2018, Dong Hyun Sohn [17] |
| CD163, CD206 | Positive association with disease activity, treatment response | Prospective study | 2018, Line Dam Heftdal [18] |
| CD27-CD38lowCD21low B cells | Positive association with disease activity |
Cross-sectional study | 2021, Rick Wilbrink [19] |
| circRNA hsa_circ_0079787 | Positive association with diagnosis, disease activity |
Cross-sectional study | 2020, Qing Luo [20] |
| Circulating microRNAs | Positive association with disease activity Positive association with diagnosis and disease activity |
Prospective study Cross-sectional study |
2020, Qing Luo [20] 2018, Carlos Perez-Sanchez [21] |
| Complement component C3 | Positive association with disease activity and cardiovascular risk |
Cross-sectional study | 2020, Ivan Arias de la Rosa [22] |
| CRP to albumin ratio (CAR) | Positive association with disease activity Positive association with disease activity |
Retrospective study Cross-sectional study |
2021, Zheng Zhong [23] 2021, Melih Pamukcu [24] |
| Dickkopf homologue-1 (Dkk-1) | Positive association with radiographic progression |
Prospective study | 2019, Zhonghai Zhao [25] |
| Bone morphogenetic proteins (BMPs) and Dkk-1 | Positive association with disease activity |
Prospective study | 2018, Hsien-Tzung Liao [26] |
| Drug-neutralizing Antibodies against TNF-α | Positive association with treatment response | Cross-sectional study | 2020, Krasimir Kraev [27] |
| ERAP1 (rs2287987, rs30187, rs27044), ERAP2 (rs2248374) | Positive association with diagnosis |
Case-control study | 2019, Andrzej Wiśniewski [28] |
| Erythrocyte sedimentation rate (ESR) ESR + Interleukin (IL)-6 |
Positive association with radiographic progression Positive association with treatment response |
Retrospective study Prospective study |
2018, Kwi Young Kang [29] 2019, Yidian Dong [30] |
| Eukaryotic translation elongation factor 1 epsilon 1 (EEF1E1) | Positive association with diagnosis |
Prospective study | 2019, Xutao Fan [31] |
| Fecal calprotectina and anti-Saccharaomyces cerevisiae antibodies (ASCA) | Positive association with disease activity |
Cross-sectional study | 2019, Tor Olofsson [32] |
| Fibrinogen-to-albumin ratio (FAR) | Positive association with disease activity |
Retrospective study | 2020, Meng Liu [33] |
| Galectin-3 | Positive association with disease activity |
Prospective study | 2019, Ming-Yu Cao [34] |
| Galectin-3, soluble suppression-of-tumorogenity-2 (sST2) (cardiac fibrosis), hsCRP | Positive association with cardiovascular risk |
Prospective study | 2018, Demet Ozkaramanli Gur [35] |
| H-ficolin, L-ficolin | Positive association with diagnosis |
Cross-sectional cohort | 2020, Anne Troldborg [36] |
| Hepatocyte growth factor (s-HGF) |
Positive association with radiographic progression Positive association with radiographic progression |
Prospective cohort study Prospective study |
2021, Anna Deminger [37] 2019, Liset Torres [38] |
| HLA B-27 antigen | Positive association with diagnosis Positive association with diagnosis Positive association with diagnosis |
Prospective study Prospective study Prospective study |
2019, Nelly Ziade [39] 2018, Chong Seng Edwin Lim [40] 2021, Henriëtte M Y de Jong [41] |
| Interleukin (IL)-31 | Positive association with radiographic progression |
Longitudinal prospective cohort study | 2018, Nicolas Rosine [42] |
| IL-33 | Positive association with disease activity and treatment response | Prospective study | 2021, Milena Iwaszko [43] |
| IL-12B and IL-6R | Positive association with diagnosis and prognosis | Prospective cohort study | 2018, Wen-Feng Ruan [44] |
| IL-22 | Positive association with diagnosis |
Retrospective study | 2022, Michal Sagiv [45] |
| IL-17 IL-23 and IL-17 |
Positive association with diagnosis Positive association with diagnosis |
Cross-sectional study Case-control study |
2020, Dalia S. Saif [46] 2018, Jacob Sode [47] |
| Leptin | Positive association with radiographic progression Positive association with radiographic progression |
Longitudinal prospective study Prospective study |
2017, Ji-Heg Park [48] 2019, Judith Rademacher [49] |
| Leptin + high molecular weight adiponectin + VEGF | Positive association with radiographic progression |
Cross-sectional study | 2019, Judith Rademacher [49] |
| LINC00311 | Positive association with diagnosis and disease activity |
Prospective study | 2019, Hongfa Zhong [50] |
| Lipocalin 2 (LCN 2), Oncostatin M (OSM) | Positive association with disease activity and treatment response | Longitudinal observational study | 2021, Florence W.L Tsui [51] |
| Metalloproteinase (MMP)-degraded collagen type I (C1M), type II (C2M), type III (C3M), and type IV (C4M2) | Positive association with disease activity |
Prospective cohort study | 2019, Markéta Husšáková [52] |
| Neutrophil extracellular trap (NET) | Positive association with disease activity and treatment response | Cross-sectional study, case report | 2020, Patricia Ruiz-Limon [53] |
| Omentin-1 | Positive association with cardiovascular risk |
Prospective study | 2020, Fernanda Genre [54] |
| Osteoprotegerin (OPG) and sclerostin (SCL) | Positive association with cardiovascular risk |
Prospective study | 2018, Fernanda Genre [55] |
| Pentraxin 3 | Positive association with disease activity |
Cross-sectional study | 2018, Renato Nisihara [56] |
| Procollagen I N-terminal peptide | Positive association with disease activity |
Cross-sectional study | 2022, Xuegang Li [57] |
| Sclerostin and antisclerostin antibody | Positive association with gastrointestinal risk Positive association with diagnosis Positive association with radiographic progression |
Prospective study Case-control study Prospective study |
2018, Michele Maria Luchetti [58] 2018, Perrota Fabio Massimo [59] 2019, Judith Rademacher [49] |
| Semaphorin 3A (Sema 3A) | Positive association with disease activity Positive association with treatment response |
Prospective study Prospective study |
2019, Hsien-Tzung Liao [60] 2017, Fabio Massimo Perrotta [61] |
| Serum amyloid A1 (SAA1) | Positive association with diagnosis |
Prospective study | 2020, Shijia Liu [62] |
| Serum calprotectin | Positive association with disease activity Positive association with treatment response Positive association with cardiovascular risk Positive association with radiographic progression |
Prospective study Prospective study Prospective study Prospective study |
2020, Matthias Jarlborg [63] 2019, Hua Hu [64] 2018, Fernanda Genre [65] 2022, Judith Rademacher [66] |
| Serum miR-214 | Positive association with disease activity |
Prospective study | 2019, Hyun Yi Kook [67] |
| Tenascin-C (TNC) | Positive association with disease activity Positive association with disease activity |
Prospective study Prospective study |
2020, Kristyna Bubova [68] 2018, Latika Gupta [69] |
| Vaspin | Positive association with cardiovascular risk |
Prospective study | 2021, Javier Rueda-Gotor [70] |
| Vimentin | Positive association with radiographic progression |
Prospective study | 2019, Anne Sofie Siebuhr [71] |
| Visfatin | Positive association with cardiovascular risk Positive association with disease activity |
Prospective study Prospective study |
2021, Rabia Aydogan Baykara [72] 2022, Judith Rademacher [66] |
This entry is adapted from the peer-reviewed paper 10.3390/ijms231911561
This entry is offline, you can click here to edit this entry!
