Local inflammation in axial spondyloarthritis (axSpA) leads to the release of collagen metabolites from the disease-affected tissue. We investigated whether collagen metabolites were associated with disease activity and could distinguish non-radiographic(nr)-axSpA from ankylosing spondylitis (AS). A total of 193 axSpA patients (nr-axSpA, n = 121 and AS, n = 72) and asymptomatic controls (n = 100) were included. Serum levels of metalloproteinase (MMP)-degraded collagen type I (C1M), type II (C2M), type III (C3M) and type IV (C4M2) were quantified by enzyme-linked immunosorbent assay (ELISA). All metabolites were higher in axSpA than in controls (all p < 0.001). Serum levels of C1M, C3M, and C4M2 were increased in AS compared to nr-axSpA (43.4 ng/mL vs. 34.6; p < 0.001, 15.4 vs. 12.8; p = 0.001, and 27.8 vs. 22.4; p < 0.001). The best metabolite to differentiate between axSpA and controls was C3M (AUC 0.95; specificity 92.0, sensitivity 83.4). C1M correlated with ASDAS-CRP in nr-axSpA (ρ = 0.37; p < 0.001) and AS (ρ = 0.57; p < 0.001). C1M, C3M, and C4M2 were associated with ASDAS-CRP in AS and nr-axSpA after adjustment for age, gender, and disease duration. Serum levels of collagen metabolites were significantly higher in AS and nr-axSpA than in controls. Moreover, the present study indicates that collagen metabolites reflect disease activity and are useful biomarkers of axSpA.

• MeSH
• ankylózující spondylitida krev   diagnóza   MeSH
• biologické markery krev   MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• fibrilární kolageny metabolismus   MeSH
• kolagen typ II metabolismus   MeSH
• kolagen typ III metabolismus   MeSH
• kolagen typu I metabolismus   MeSH
• kolagen typu IV metabolismus   MeSH
• lidé MeSH
• spondylartritida krev   diagnóza   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Activity and chronicity of kidney involvement in ANCA-associated vasculitis (AAV) can be currently reliably evaluated only by kidney biopsy. In this study, we measured a panel of serum and urinary biomarkers collected at the time of kidney biopsy and hypothesized that they could reflect specific histopathological parameters in the biopsy and help to predict prognosis. METHODS: We examined a cohort of 45 patients with AAV and 10 healthy controls. Biomarker levels (DKK-3, CD163, EGF, PRO-C6 and C3M) were measured in this study by ELISA. Biopsies were scored with a scoring system for AAV (focal x crescentic x sclerotic x mixed class) and interstitial fibrosis was quantified. RESULTS: Levels of urinary DKK-3, CD163, EGF, PRO-C6 and C3M significantly differed among biopsy classes in AAV, with urinary DKK-3 and PRO-C6 levels being highest in the sclerotic class and lowest in the focal class, urinary CD163 levels highest in the crescentic class and urinary C3M levels highest in the focal class. Moreover, the urinary biomarkers were able to discriminate focal biopsy class from the other classes. Urinary DKK-3, EGF, PRO-C6 and C3M levels measured at the time of biopsy were also significantly related to the extent of fibrosis and to the final kidney function at the end of follow-up. CONCLUSIONS: This small pilot study suggests that selected urinary biomarkers of fibrosis and inflammation may reflect changes in the kidney biopsy and be prognostic of kidney outcome in patients with AAV.

• MeSH
• ANCA-asociované vaskulitidy * patologie   MeSH
• biologické markery moč   MeSH
• epidermální růstový faktor MeSH
• fibróza MeSH
• ledviny patologie   MeSH
• lidé MeSH
• pilotní projekty MeSH
• protilátky proti cytoplazmě neutrofilů * MeSH
• zánět patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Kidney fibrosis is the hallmark of chronic kidney disease (CKD) and is characterized by an imbalanced extracellular matrix (ECM) remodeling. Collagen type III is one of the main ECM components of the interstitial matrix of the kidney. We hypothesized that measuring three biomarkers of collagen type III reflecting different aspects of this protein turnover (C3M, C3C, and PRO-C3) may provide different information about the fibrotic burden in patients with IgA nephropathy (IgAN). We examined a cohort of 134 patients with IgAN. The three collagen type III biomarkers were measured in serum (S) and in urine (U) samples taken on the same day before kidney biopsy was performed. Biopsies were evaluated for interstitial fibrosis and tubular atrophy, according to the Banff and MEST-C scores. S-PRO-C3 and S-C3C correlated with the degree of fibrosis in the biopsy, whereas U-C3M/Cr had an inverse correlation with fibrosis. U-C3M/Cr had the highest discrimination ability for advanced fibrosis, which was maintained after adjustment for the other collagen type III biomarkers, proteinuria, and serum creatinine. The data presented in this study indicate that measuring the different fragments of the same ECM protein and in different matrices provides a variety of information regarding pathological kidney tissue alterations in patients with IgAN.

• MeSH
• biologické markery MeSH
• fibróza MeSH
• IgA nefropatie * patologie   MeSH
• kolagen typ III MeSH
• komplement C3 analýza   MeSH
• ledviny patologie   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

U pacientů s axiální spondyloartritidou (axSpA) je nedostatek spolehlivých ukazatelů, které by měly vypovídající hodnotu při hodnocení rizika vzniku, aktivity nebo progrese onemocnění, případně odpovědi na léčbu, a zároveň by se daly jednoduše a levně měřit. Existuje mnoho studií zabývajících se detekcí právě takovýchto markerů. Do souvislosti se zvýšeným nebezpečím propuknutí nemoci je nejčastěji dáván antigen HLA-B27, slibně se ukazují i některé varianty genu pro aminopeptidázu endoplazmatického retikula – 1 (ERAP1). V rámci hodnocení aktivity, možné radiografické progrese či odpovědi na anti-TNFα terapii bývají biomarkery obvykle tříděny do dvou hlavních skupin. Jedná se o biomarkery, které mají vztah k zánětlivému procesu anebo k metabolismu kloubních tkání. C-reaktivní protein (CRP) spolu se sedimentací erytrocytů (FW) jsou základní oporou skupiny markerů reflektující zánětlivou aktivitu, mají však nízkou senzitivitu a specificitu. Za ukazatele zánětlivé aktivity lze považovat také sérový amyloid (SAA) nebo interleukin-6 (IL-6), metaloproteináza-3 (MMP-3) a další markery jako calprotectin (S100A8/A9), dickkopf-1 (DKK-1) nebo cytotoxický s T-lymfocyty asociovaný protein 4 (sCTLA-4), případně degradační peptid kolagenu typu III (C3M). Potenciálními prediktory radiografické progrese je kromě MMP-3 například sclerostin, DKK-1 nebo některé kostní morfogenní proteiny (BMP-2 a 4). Dobrou odpověď na léčbu můžeme předpokládat zejména u pacientů s vyššími hodnotami reaktantů akutní fáze a již přítomným strukturálním poškozením páteře. Biomarkerů asociovaných s axSpA vychází ze studií velké množství, díky nim jsme schopni nahlédnout alespoň částečně do patogeneze tohoto onemocnění a určit další možné přístupy k léčbě. Většina studií má však své limitace jako například nedostatečné množství pacientů ve zkoumaných kohortách, rozdílné standardy a techniky pro stanovení biomarkerů v séru a v neposlední řadě chybějící multivariační analýzy. Cílem této práce bylo vypracování přehledu dostupných sérových laboratorních markerů asociovaných s axSpA.

Axial spondyloarthritis (axSpA) lacks reliable indicators that would have predictive value in assessing risk of development of the disease, disease activity or progression or response to treatment, and that could also be measured easily and inexpensively. There are many studies focusing on the detection of such markers. An increased risk of disease onset is usually associated with HLA-B27 antigen; furthermore, promising associations have been demonstrated with some variants of the endoplasmic reticulum aminopeptidase - 1 (ERAP1) gene. Biomarkers used for the assessment of disease activity and progression or response to anti-TNF therapy are usually classified into two main groups: biomarkers that are related to the inflammatory process or to metabolism of the joint tissues. C-reactive protein (CRP) along with erythrocyte sedimentation rate (ESR) are the basic pillars of the group of markers reflecting inflammatory activity. However, they have low sensitivity and specificity. Other indicators of inflammatory activity include serum amyloid A (SAA) or interleukin-6 (IL-6), metalloproteinase-3 (MMP-3) and other markers as calprotectin (S100A8 / A9), dickkopf-1 (DKK-1) or cytotoxic T lymphocyte-associated protein-4 (sCTLA-4) or the type III collagen degradation peptide (C3M). Potential predictors of radiographic progression include MMP-3, sclerostin, DKK-1 and certain types of bone morphogenic proteins (BMP-2 and 4). Good response to treatment can be expected especially in patients with higher levels of acute phase reactants and pre-existing structural damage to the spine. A lot of available biomarkers associated with axSpA are based on a large number of studies. Thanks to them we are able to at least partially elucidate the pathogenesis of this disease and to identify other possible approaches to treatment. Most studies, however, have its limitations, such as insufficient number of patients in the studied cohorts, different standards and techniques for the determination of biomarkers in serum, and finally absence of multivariate analysis. The aim of this work was to develop an overview of available serum laboratory markers associated with axSpA.

• MeSH
• adipokiny MeSH
• biologické markery * MeSH
• C-reaktivní protein MeSH
• cytokiny MeSH
• kosti a kostní tkáň metabolismus   MeSH
• kostní morfogenetické proteiny MeSH
• lidé MeSH
• matrixové metaloproteinasy MeSH
• proteiny S100 MeSH
• receptory vaskulárního endoteliálního růstového faktoru MeSH
• spondylartritida * diagnóza   klasifikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

We evaluated biomarkers related to kidney fibrosis for the outcome of patients with IgA nephropathy (IgAN). Clinical parameters (estimated glomerular filtration rate, hypertension, proteinuria) and histological findings were assessed in 134 patients with IgAN at the time of diagnosis and followed up prospectively (mean follow-up time, 56.5 months). We measured biomarkers of collagen and laminin turnover in serum and urine collected at the time of kidney biopsy using a novel enzyme-linked immunosorbent assay. Linear discriminant analysis and logistic regression models were used to predict the patient's kidney outcome. Five serum and urine biomarkers of laminin and collagen turnover (sLG1M, sPRO-C3, sPRO-C6, uPRO-C6/Cr, uC3M/Cr) could significantly differentiae IgAN patients with a worse prognosis. Clinical parameters (glomerular filtration rate (GFR), proteinuria) distinguished patients at risk of IgAN progression with a specificity of 87.3% and a sensitivity of 45.2% (area under the curve-AUC 0.751). The addition of the biomarkers significantly increased the prognostic ability with a specificity of 85.1% and a sensitivity of 73.3% (AUC 0.905). We have identified three serum (sLG1M, sPRO-C3, sPRO-C6) and two urinary markers (uPRO-C6/Cr, u-C3M /Cr) that significantly improve the prognostic ability of markers of kidney function to identify an IgAN patient's risk of progressing to ESKD.

• MeSH
• biologické markery MeSH
• fibróza MeSH
• hodnoty glomerulární filtrace MeSH
• IgA nefropatie * diagnóza   patologie   MeSH
• laminin MeSH
• ledviny patologie   MeSH
• lidé MeSH
• proteinurie patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH