CSF levels of HoxB3 and YKL-40 may predict conversion from clinically isolated syndrome to relapsing remitting multiple sclerosis

Tamam, Yusuf; Güneş, Betül; Akbayır, Ece; Kızılay, Tuğçe; Karaaslan, Zerrin; Koral, Gizem; Düzel, Berna; Küçükali, Cem İ̇smail; Gündüz, Tuncay; Kürtüncü, Murat; Yılmaz, Vuslat; Tüzün, Erdem; Türkoğlu, Recai

doi:10.1016/j.msard.2020.102697

Cited by 13 publications

(6 citation statements)

References 28 publications

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“…Hox proteins have been associated with different fields of human medicine. The HoxB3 was identified as a potential biomarker for osteoarthritis [ 37 ] and might be used for the prediction of clinically isolated syndrome progress to relapsing-remitting multiple sclerosis [ 38 , 39 ]. The aberrant expression of HoxB3 might promote Parkinson’s disease via dysregulating sphingolipid and glutathione metabolism [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Investigation of HoxB3 and Growth Factors Expression in Placentas of Various Gestational Ages

Kreicberga

Junga

Pilmane

2021

JDB

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An evaluation of transforming growth factor beta (TGFβ), hepatocyte growth factor (HGF), basic fibroblast growth factor (FGF-2), fibroblast growth factors receptor 1 (FGFR1) and Hox-positive cells in the human placenta, and their correlation with gestational time at delivery and pregnancy outcomes, may provide not only a better understanding of the role of Hox genes and growth factors in human development, but also may be of clinical importance in reproductive medicine. This study analyzed the immunohistochemical identification of TGFβ, HGF, FGF-2, FGFR1 and HoxB3 in placentas of various gestational ages. We found few (+) TGFβ, moderate (++) FGF-2 and numerous (+++) HGF and FGFR1 positive structures. Occasional (0/+) to numerous (+++) HoxB3-positive structures were detected in different types of placental cells specifically, cytotrophoblasts, syncytiotrophoblast, extravillous trophoblasts, and Höfbauer cells. Correlating the appearance of HoxB3 staining in placentas with neonatal parameters, we found a statistically significant negative correlation with ponderal index (r = −0.323, p = 0.018) and positive correlation with neonate body length (r = 0.541, p = 0.046). The number of HoxB3-positive cells did not correlate with growth factors and gestational age, but with neonatal anthropometrical parameters, indicating the role of HoxB3 not only in placental development, but also in the longitudinal growth of the fetus. TGFβ and FGF-2 did not play a significant role in the development of the placenta beyond 22nd week of pregnancy, while HGF and FGFR1 immunoreactive cells increased with advancing gestation, indicating increasingly evolving maturation (growth, proliferation) of the placenta, especially in the third trimester.

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Section: Discussionmentioning

confidence: 99%

Investigation of HoxB3 and Growth Factors Expression in Placentas of Various Gestational Ages

Kreicberga

Junga

Pilmane

2021

JDB

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“…Several studies also showed CIS patients to have higher CHI3L1 levels compared to HCs, suggesting its overexpression already from the beginning of the disease, highlighting its potential as a prognostic biomarker. Accordingly, the elevation of CHI3L1 in both the CSF and sera of CIS patients was an independent predictor of both disease conversion and more rapid development of disability [145][146][147][148] . On the other hand, there is no significant difference in CHI3L1 levels between RR and progressive subtypes of MS 144 .…”

Section: Copeptinmentioning

confidence: 93%

Emerging Biomarkers of Multiple Sclerosis in the Blood and the CSF: a Comprehensive Review of the Literature with a Focus on Neurofilaments and Therapeutic Considerations

Biernacki¹,

Kokas²,

Sandi³

et al. 2022

Preprint

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Introduction: multiple sclerosis (MS) is the most common immune-mediated chronic neurodegenerative disease of the central nervous system (CNS), affecting young people. Due to the permanent disability, cognitive impairment, and the enormous detrimental impact MS can exert on the patients’ health-related quality of life. It is of great importance to recognise it in time and commence adequate treatment at an early stage. The currently used disease-modifying therapies (DMT) aim to reduce disease activity and thus halt disability development, which in current clinical practice are monitored by clinical and imaging parameters but not by biomarkers found in blood and/or the cerebrospinal fluid (CSF). Both clinical and radiological measures routinely used to monitor disease activity lack information on the fundamental pathophysiological features and mechanisms of MS. Furthermore, they lag behind the disease process itself. By the time a clinical relapse becomes evident or a new lesion appears on the MRI scan, potentially irreversible damage has already occurred in the CNS. In recent years several biomarkers that previously have been linked to other neurological and immunological diseases have received increased attention in MS. Additionally, other novel, potential biomarkers with prognostic and diagnostic properties have been detected in the CSF and blood of MS patients. Areas covered: in this review, we summarise the most up to date knowledge and research conducted on the already known and most promising new biomarker candidates found in the CSF and blood of MS patients. Author commentary: the current diagnostic criteria of MS rely on three pillars; MRI imaging, clinical events and the presence of oligoclonal bands in the CSF (which was reinstated into the diagnostic criteria by the most recent revision). Even though the most recent McDonald criteria made the diagnosis of MS faster than the prior iteration, it is still not an infallible diagnostic toolset, especially at the very early stage of clinically isolated syndrome. Together with the gold standard MRI and clinical measures, ancillary blood and CSF biomarkers may not just improve diagnostic accuracy and speed but very well may become agents to monitor therapeutic efficacy and make even more personalised treatment in MS a reality in the near future. The major disadvantage of these biomarkers in the past has been the need to obtain CSF to measure them. However, the recent advances in extremely sensitive immunoassays made their measurement possible from peripheral blood even when present only in minuscule concentrations. This should mark the beginning of a new biomarker research and utilisation era in MS.

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“…Chitinase-3-like 1 (CHI3L1/YKL-40) is a pro-inflammatory secreted glycoprotein of unclear function that has been purported as a potential marker of reactive astrocytes and microglia/macrophages (Figure 2), though it is also expressed on peripheral cells, including monocytes, chondrocytes, neutrophils, and vascular smooth muscle cells, among other cell types [95,96]. Initial studies suggested that CSF CHI3L1 is primarily intrathecally produced and that CSF levels do not correlate with serum levels [95,97,98]. Elevated CSF CHI3L1 has also been shown to associate with higher risk and faster time for conversion from CIS to MS, faster development of disability, brain MRI lesions, and brain atrophy and may decrease with DMT initiation [83,[95][96][97][98][99][100].…”

Section: Chitinase-3-likementioning

confidence: 99%

“…Initial studies suggested that CSF CHI3L1 is primarily intrathecally produced and that CSF levels do not correlate with serum levels [95,97,98]. Elevated CSF CHI3L1 has also been shown to associate with higher risk and faster time for conversion from CIS to MS, faster development of disability, brain MRI lesions, and brain atrophy and may decrease with DMT initiation [83,[95][96][97][98][99][100]. A recent meta-analysis found that CSF CHI3L1 levels were higher in patients with MS compared to healthy controls, higher in people with PPMS compared to both RRMS and SPMS, and higher in those with CIS who converted to MS compared to those that did not convert [101].…”

Section: Chitinase-3-likementioning

confidence: 99%

Emerging imaging and liquid biomarkers in multiple sclerosis

et al. 2023

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The advent of highly effective disease modifying therapy has transformed the landscape of multiple sclerosis (MS) care over the last two decades. However, there remains a critical, unmet need for sensitive and specific biomarkers to aid in diagnosis, prognosis, treatment monitoring, and the development of new interventions, particularly for people with progressive disease. This review evaluates the current data for several emerging imaging and liquid biomarkers in people with MS. MRI findings such as the central vein sign and paramagnetic rim lesions may improve MS diagnostic accuracy and evaluation of therapy efficacy in progressive disease. Serum and cerebrospinal fluid levels of several neuroglial proteins, such as neurofilament light chain and glial fibrillary acidic protein, show potential to be sensitive biomarkers of pathologic processes such as neuro‐axonal injury or glial‐inflammation. Additional promising biomarkers, including optical coherence tomography, cytokines and chemokines, microRNAs, and extracellular vesicles/exosomes, are also reviewed, among others. Beyond their potential integration into MS clinical care and interventional trials, several of these biomarkers may be informative of MS pathogenesis and help elucidate novel targets for treatment strategies.

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CSF levels of HoxB3 and YKL-40 may predict conversion from clinically isolated syndrome to relapsing remitting multiple sclerosis

Cited by 13 publications

References 28 publications

Investigation of HoxB3 and Growth Factors Expression in Placentas of Various Gestational Ages

Investigation of HoxB3 and Growth Factors Expression in Placentas of Various Gestational Ages

Emerging Biomarkers of Multiple Sclerosis in the Blood and the CSF: a Comprehensive Review of the Literature with a Focus on Neurofilaments and Therapeutic Considerations

Emerging imaging and liquid biomarkers in multiple sclerosis

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