From gene expression to serum proteins: biomarker discovery in ankylosing spondylitis

2008 ◽  
Vol 69 (01) ◽  
pp. 297-300 ◽  
Author(s):  
N Haroon ◽  
F W L Tsui ◽  
F D O’Shea ◽  
B Chiu ◽  
H W Tsui ◽  
...  

Objectives:Studying post-infliximab gene expression changes could provide insights into the pathogenesis of ankylosing spondylitis (AS).Methods:Gene expression changes were screened by microarray on peripheral blood RNA of 16 AS patients at baseline and 2 weeks post-infliximab, and selected results were confirmed by quantitative real-time (qRT)–PCR. Corresponding serum-soluble LIGHT (sLIGHT) was estimated by ELISA and the fold change in sLIGHT was correlated to the fold change in erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and the Bath AS disease activity index.Results:Post-infliximab, 69% of the patients (11/16) achieved an ASAS20 response. Six candidate genes were differentially expressed by microarray; four of which were validated by qRT–PCR. sLIGHT showed the most significant difference. There was good correlation of baseline sLIGHT with CRP (R  =  0.60; p = 0.01) and ESR (R  =  0.51; p = 0.04). The fold change in sLIGHT correlated with change in both CRP (R  =  0.71, p = 0.002) and ESR (R  =  0.77, p<0.001).Conclusion:LIGHT is significantly downregulated by infliximab. sLIGHT correlated well with changes in inflammatory markers.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1629.2-1629
Author(s):  
K. Ben Abdelghani ◽  
Y. Gzam ◽  
A. Fazaa ◽  
S. Miladi ◽  
K. Ouenniche ◽  
...  

Background:Axial spondyloarthritis (ax-SpA) is a chronic rheumatic disease that mainly affects men. However, the female form of ax-SpA remains insufficiently studied.Objectives:The aim of this study was to determine the clinical characteristics, the disease activity and the functional impact of female ax-SpA in comparison with male ax-SpA.Methods:This is a retrospective study including patients diagnosed with ax-SpA fulfilling the criteria of the Assessment of SpondyloArthritis international Society (ASAS) 2009.Clinical parameters, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Bath ankylosing spondylitis disease activity index (BASDAI) and Bath ankylosing spondylitis functional index (BASFI) were compared between groups of female and male ax-SpA.Results:Two hundred ax-SpA patients were included with 31% of female (n=62) and a mean age of 43,3 ± 11,2 years.The mean age at onset of symptoms was 31,8 ± 8,9 years for women and 25,3 ± 9,1 years for men (p <0,0001). The mean age at diagnosis was 36,4 ± 9,6 years for women and 31,7 ± 10,4 years for men (p = 0,003). Ax-SpA with juvenile onset was noted in 1,7% of women and 12,1% of men (p = 0,02). Male ax-SpA were significantly more smokers (46.8% vs 5.4%; p <0.001). The mean duration of morning stiffness was 11,3 ± 9,2 minutes for women versus 21,6 ± 19,3 minutes for men (p = 0,005).The mean ESR was 42,4 ± 29,8 mm for women and 28,3 ± 23,4 mm for men (p = 0,001). Radiographic sacroiliitis was present in 69,3% of women versus 84,7% of men (p = 0,01). The use of anti-TNF alpha was less frequent in women (29% vs 48,5%; p = 0,01).Our study didn’t found a statistically significant difference in peripheral manifestations, extraarticular manifestations, CRP, BASDAI and BASFI between the two groups.Conclusion:Female ax-SpA seems to have a better prognosis than male with older age in disease onset, less inflammation, less radiographic sacroiliitis and less use of biological treatments.References:[1]Rusman T, et al. Curr Rheumatol Rep. 2018; 20(6).[2]Siar N, et al. Curr Rheumatol Rev. 2019;Disclosure of Interests:None declared


RMD Open ◽  
2021 ◽  
Vol 7 (2) ◽  
pp. e001510
Author(s):  
Matthew Turk ◽  
Kieran Murray ◽  
Yousef Alammari ◽  
Aine Gorman ◽  
Francis Young ◽  
...  

ObjectiveThe role of alcohol in inflammatory disease remains debated. This study explores the relationship between alcohol and disease activity in patients with inflammatory arthritis.MethodsPatients attending a rheumatology clinic between 2010 and 2020 were prospectively followed. Information on demographics, alcohol use, smoking habits and disease outcome measures were collected from these patients. Statistical analysis included univariate and multivariate linear and binary logistic regressions, Mann-Whitney U tests and one-way analysis of variance with Tukey’s honest significant difference (HSD) test.ResultsOf the 979 analysed patients, 62% had rheumatoid arthritis (RA), 26.7% had psoriatic arthritis (PsA) and 11.2% had ankylosing spondylitis. Mean DAS28-CRP (Disease Activity Score 28 - C-reactive protein) in RA and PsA at 1 year was 2.96±1.39, and 64.2% of patients were in remission (DAS28-CRP ≤2.6 or BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) ≤4). Both male gender and risky drinking (>15 units of weekly alcohol) were significantly associated with remission. Compared with women, men had an OR of 1.8 (1.1, 2.5) (p=0.034) for any alcohol consumption and 6.9 (4.7, 9.1) (p=0.001) for drinking at least 15 weekly drinks. When adjusted for gender, there was no association between alcohol and disease activity. Yet, when adjusted for alcohol consumption, gender still significantly influenced disease activity.ConclusionWhile it may appear that alcohol is linked to remission in inflammatory arthritis, when adjusted for gender, it is not. Men with inflammatory arthritis drink significantly more than women and have less severe disease activity.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1627.2-1627
Author(s):  
F. I. Abdelrahman ◽  
M. Mortada

Background:Ankylosing spondylitis (AS) is a destructive inflammatory disease which was reported to have the longest diagnostic delay among the inflammatory rheumatic disease. This lag period have a great impact on the clinical outcome and socioeconomic state of the patients. With the advent of tumor necrosis factor-α (TNF-α) inhibitors, early diagnosis in AS has become important(1).Objectives:to evaluate the period from symptom onset to diagnosis of AS in Egyptian patients and to examine possible reasons for delayed diagnosis and its impact on the economic and social life of the patients.Methods:The study included 87 AS patients diagnosed according to the Assessment of Spondyloarthritis international Society (ASAS) criteria (2). A face-to-face interview was applied to take medical history, and a questionnaire that contains some clinical aspects of disease was used. Diagnosis delay was described as the gap between first AS symptom and correct diagnosis of AS. Clinical and functional assessment of axial SpA measured by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI). The direct medical cost during years of delay (including costs of medical consultations, medications, investigations, physiotherapy and surgical treatment) had been estimated by Egyptian pound.Results:The study included 87 AS patients with mean age (30.03±8.3), 70 male (80.5%) and 17 female (19.5%).Mean delay in diagnosis was(5.7 ±4.9) years. Mean of diagnostic delay for patient diagnosed before 2010 is (14±4.4) and that of patients diagnosed after 2010 is (3.5±1.8) with significant difference between both (p value<0.0001). The main cause of delay was incorrect diagnosis as follow degenerative disc disease (43/87, 49.4%), non-specific back pain (31/87, 35.6%), rheumatoid arthritis (10/87,11.5%), rheumatic fever (2/87, 2.3%) and tuberculosis of spine (1/87, 1.1%). The mean of the medical visits was (6±5.4). Most incorrect initial diagnoses were made by orthopedicians (57.9%), followed by neurologists (22.2%) followed by rheumatologist (10%) and general phyisicians (9.9%). Absence of extra-articular manifestations, negative family history and juvenile age are significantly associated with diagnostic delay. Delay in diagnosis is significantly associated with higher disease activity index(BASDAI), functional index (BASFI), and damage index(BASMI). The mean of the costs during years of delay is (15671.3±546.1) with the mean of cost per each year delay (660.9±6.6) with high significant association between the cost and longer delay in diagnosis (<0.0001). Regarding work ability, we found that(32.2%) are fit for work, unfit (29.9%), partially fit (37.9%) with high significant difference between ability of work and shorter delay. Regarding social effect, 40.2 % of patients developed negative effect on social life with significant association to diagnostic delay (0.004).Conclusion:Our study confirmed the importance of early diagnosis of AS due to its impact on patient’s health outcome and socioeconomic state.We recommend to increase the awareness about the disease among healthcare professionals in our region.References:[1]Sykes M. et al: Diagnostic delay in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis; Ann Rheum Dis.2015;74:e44.[2]Rudwaleit M. et al: The development of Assessment of Spondyloarthritis international Society classification criteria for axial spondyloarthritis; Ann Rheum Dis, 68 (2009), pp.777-783.Disclosure of Interests:None declared


2020 ◽  
Vol 56 (1) ◽  
pp. 51-58
Author(s):  
Filip Mirić ◽  
Srđan Novak

Cilj: Svrha rada bila je utvrditi i usporediti učinkovitost te preživljenje TNF-α (engl. tumor necrosis factor-α) inhibitora (adalimumab, golimumab, infliksimab) tijekom trogodišnjeg praćenja u liječenju ankilozantnog spondilitisa. Materijali i metode: Ovim retrospektivnim istraživanjem obuhvaćena je skupina od 29 ispitanika koji su primili prvi biološki lijek na Odjelu reumatologije i kliničke imunologije Kliničkog bolničkog centra Rijeka. Započeli su s biološkim lijekom u razdoblju od siječnja 2009. do lipnja 2015. godine i bili praćeni tri godine nakon početka terapije. Parametri kojima se pratila aktivnost bolesti bili su BASDAI (engl. Bath Ankylosing Spondylitis Disease Activity Index), BASFI (engl. Bath Ankylosing Spondylitis Functional Index), CRP (engl. C reactive protein) i VAS (engl. Visual Analogue Scale), a mjereni su prije početka terapije te nakon 3 i 36 mjeseci od njenog uvođenja. Rezultati: Od ukupno 29 ispitanika, 11 ih je bilo na adalimumabu, 10 na golimumabu, a 8 na infliksimabu. Analizirajući parametre uključene u ovo istraživanje (BASDAI, BASFI, CRP, VAS), ni u jednom promatranom periodu nije zabilježena statistički značajna razlika između ispitanika s obzirom na primijenjeni TNF-α inhibitor (svi p &gt; 0,05). Ukupno trogodišnje preživljenje TNF-α inhibitora iznosilo je 75,8 %. Kod ispitanika liječenih adalimumabom trogodišnje preživljenje iznosilo je 72,8 %, za golimumab 80 % te infliksimab 75 % (svi p &gt; 0,05). Zaključci: Uspoređujući ispitanike liječene adalimumabom, golimumabom i infliksimabom u prvoj liniji biološke terapije, naše istraživanje na malom broju ispitanika pokazalo je kako nema značajne razlike u njihovoj učinkovitosti i preživljenju.


mSystems ◽  
2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Ming Li ◽  
Bingbing Dai ◽  
Yawei Tang ◽  
Lei Lei ◽  
Ningning Li ◽  
...  

ABSTRACT Intestinal bacterial dysbiosis has been increasingly linked to ankylosing spondylitis (AS), which is a prototypic and best studied subtype of spondyloarthritis (SpA). Fungi and bacteria coexist in the human gut and interact with each other. Although they have been shown to contribute actively to health or disease, no studies have investigated whether the fungal microbiota in AS patients is perturbed. In this study, fecal samples from 22 AS patients, with clinical and radiographic assessments, and 16 healthy controls (HCs) were collected to systematically characterize the gut microbiota and mycobiota in AS patients by 16S rRNA gene- and ITS2-based DNA sequencing. Our results showed that the microbiota of AS patients was characterized by increased abundance of Proteobacteria and decreased Bacteroidetes, which was contributed by enrichment of Escherichia-Shigella, Veillonella, Lachnospiraceae NK4A136 group, and reduction of Prevotella strain 9, Megamona, and Fusobacterium. The gut mycobiota of AS patients was characterized by higher levels of Ascomycota, especially the class of Dothideomycetes, and decreased abundance of Basidiomycota, which was mainly contributed by the decease of Agaricales. Compared to HCs, decreased ITS2/16S biodiversity ratios and altered bacterial-fungal interkingdom networks were observed in AS patients. Compared with nonsteroidal anti-inflammatory drugs (NSAIDs), treating AS patients with biological agents induced obvious changes in the gut mycobiota, and this result was highly associated with disease activity indexes, including AS disease activity index (ASDAS) C-reactive protein (asCRP), erythrocyte sedimentation rate (ESR), and Bath AS disease activity index (BASDAI). In addition, altered mycobiota in AS patients was also found associated with the degree of radiographic damage. IMPORTANCE The human gut is colonized by diverse fungi (mycobiota), and fungi have long been suspected in the pathogenesis of SpA. Our study unraveled a disease-specific interkingdom network alteration in AS, suggesting that fungi, or the interkingdom interactions between bacteria and fungi, may play an essential role in AS development. However, our study is limited by sample size, and in-depth mechanism studies and additional large-scale investigations characterizing the gut mycobiome in AS patients are needed to form a foundation for research into the relationship between mycobiota dysbiosis and AS development.


2020 ◽  
Vol 26 (10) ◽  
pp. 1607-1618 ◽  
Author(s):  
Christopher R Manzella ◽  
Dulari Jayawardena ◽  
Wilfredo Pagani ◽  
Ye Li ◽  
Waddah A Alrefai ◽  
...  

Abstract Background Diagnosis and monitoring of inflammatory bowel diseases (IBDs) utilize invasive methods including endoscopy and tissue biopsy, with blood tests being less specific for IBDs. Substantial evidence has implicated involvement of the neurohormone serotonin (5-hydroxytryptamine, 5-HT) in the pathophysiology of IBDs. The current study investigated whether serum 5-HT is elevated in patients with active ulcerative colitis (UC) or Crohn’s disease (CD). Methods Serum samples were obtained from a German cohort of 96 CD and UC patients with active disease, refractory disease, or remission of disease based upon their disease activity index (DAI) and disease history. High pressure liquid chromatography with tandemmass spectrometry was used to measure 5-HT, tryptophan (TRP), and kynurenine (KYN) levels in the serum samples, and Luminex Multiplex ELISA was used to measure cytokine levels. Intestinal mucosal biopsies were obtained from a separate cohort of healthy and CD patients, and the immunoreactivity of the serotonin transporter (SERT) was determined. Results There was no statistically significant difference in TRP or KYN levels between disease categories in either UC or CD. Interestingly, 5-HT levels were significantly elevated in patients with active CD but not active UC when compared with the levels in remission or refractory disease. Serum 5-HT was superior to C-reactive protein and circulating cytokines in differentiating between disease categories in CD. Additionally, SERT immunoreactivity was decreased in the ileum and colon of patients with CD compared to healthy controls. Conclusion We have shown that the serum 5-HT can differentiate between active disease and refractory disease or remission among CD patients, emphasizing the potential suitability of serum 5-HT as an auxiliary measure in diagnosing active CD.


2019 ◽  
Vol 11 ◽  
pp. 1759720X1983232 ◽  
Author(s):  
Ferdi Yavuz ◽  
Bilge Kesikburun ◽  
Özlem Öztürk ◽  
Ümüt Güzelküçük

Background: The aim of this study was to assess the serum chitotriosidase (ChT) and neopterin levels in patients with ankylosing spondylitis (AS) and to evaluate whether serum ChT and neopterin levels are related to disease activity. Methods: A total of 86 patients with AS were included in the study. Patients were divided into two groups based on Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores: The active AS patients group included 40 patients who had a BASDAI score ⩾4. The inactive AS patients group included 46 patients who had a BASDAI score <4. We compared the serum level of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), ChT and neopterin between the two groups. Results: Active AS patients had significantly higher ESR, CRP, serum ChT and neopterin levels compared with the inactive AS patients group ( p < 0.05). Positive correlations were found between serum ChT levels and ESR ( r = 0.87, p = 0.005), and CRP levels ( r = 0.86, p = 0.006). Also, there was a positive significant correlation between serum ChT levels and BASDAI scores ( r = 0.67, p = 0.03). No correlation was found between serum neopterin levels and the BASDAI scores, ESR, and CRP levels ( p > 0.05). Higher disease activity (BASDAI score ⩾4) was found to be associated with ChT ( p = 0.012) in the multiple logistic regression analysis. Conclusion: The present study emphasized that serum ChT levels can be useful in the determination of the disease activity of AS patients.


2021 ◽  
Vol 19 ◽  
pp. 205873922110140
Author(s):  
Kai Zhang ◽  
Junhao Wang ◽  
Jinhong Chen ◽  
Zhi Li ◽  
Zhaohui Lou

The C-reactive protein to prealbumin ratio (CPR) and fibrinogen to prealbumin ratio (FPR) in serum are two emerging biomarkers. The purpose of this study is to explore the relationship between these two markers and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Scores (ASDAS). A total of 163 patients with AS and 120 healthy examinees were included in this study. The t-test and Mann-Whitney U ranking test were used to analyze the differences between groups. The spearman-test was used to analyze the correlation between erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), fibrinogen (Fib), prealbumin (PAlb), CPR, FPR, and AS disease activity in the test group. We generated the receiver operating characteristic curves (ROC) of CPR and FPR and determined the discriminating ability by calculating the area under the curve (AUC). Compared with the healthy group, ESR ( p < 0.001), CRP ( p < 0.001), Fib ( p < 0.001), CPR ( p < 0.001), and FPR ( p < 0.001) of AS patients were significantly increased, while PAlb was significantly reduced. CPR and FPR were more correlated to ASDAS-CRP. CPR was positively correlated with CRP, ESR, BASDAI, and ASDAS-CRP in AS patients ( r = 0.959, p < 0.001, r = 0.717, p < 0.001, r = 0.704, p < 0.001, r = 0.763, p < 0.001). FPR was positively correlated with CRP, ESR BASDAI, and ASDAS-CRP in AS patients ( r = 0.779, p < 0.001, r = 0709, p < 0.001, r = 0.551, p < 0.001, r = 0.763, p < 0.001). ROC showed that the AUC levels of CPR and FPR were high (AUC = 0.952 and AUC = 0.893). CPR and FPR are two promising new biological indicators for assessing disease activity in AS patients.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 723-724
Author(s):  
M. Magrey ◽  
S. Ramiro ◽  
M. Pinheiro ◽  
T. Gao ◽  
F. Ganz ◽  
...  

Background:Upadacitinib (UPA) is an oral Janus kinase inhibitor that has demonstrated efficacy and safety among patients with ankylosing spondylitis (AS) in the phase 2/3 SELECT-AXIS 1 study.1 If identified, early predictors of treatment response may inform treat-to-target strategies and optimize patient outcomes in AS.Objectives:To determine whether baseline (BL) characteristics or early responses predict clinical response at 1 year in UPA-treated patients with AS.Methods:In the double-blind, randomized, placebo (PBO)-controlled SELECT-AXIS 1 study, patients received UPA 15 mg once daily or PBO until Week 14.1 At Week 14, PBO-treated patients switched to UPA 15 mg; patients originally randomized to UPA continued UPA therapy. Data from patients in the PBO and UPA arms were combined based on overall exposure to UPA; in the switch arm, exposure was defined as current visit minus 14 weeks (time of switch). The following outcomes were assessed at 1 year: Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS[CRP]) inactive disease (ID; <1.3) and low disease activity (LDA; <2.1), Assessment of SpondyloArthritis International Society (ASAS) partial remission (PR), and ≥40% improvement in ASAS criteria (ASAS40) response. The ability of BL characteristics, efficacy at Week 12, and back pain at Week 12 to predict 1-year outcomes was assessed using a univariable logistic regression model generating odds ratios (ORs; 95% confidence intervals). LASSO regression was used to select the best-fitted multivariable model at Week 12 for each outcome measure.Results:Among 187 patients who received or switched to UPA 15 mg, 70 (37.4%), 134 (71.7%), 73 (39.0%), and 131 (70.1%) achieved ASDAS(CRP) ID, ASDAS(CRP) LDA, ASAS PR, and ASAS40, respectively, following 1 year of UPA treatment. No meaningful predictors of 1-year efficacy outcomes were identified based on BL demographics (including disease duration, gender, and human leukocyte antigen B27 status) or BL disease characteristics (including ASDAS, Bath Ankylosing Spondylitis Disease Activity Index, and CRP levels). In univariable analyses, Week 12 responses based on several disease activity measures and patient-reported outcomes (PROs), including reductions (much better improvement [MBI], ≥30/≥50/≥70% reduction, or improvement) in back pain score, along with lower scores for back pain at Week 12, were associated with the achievement of ASDAS(CRP) ID, ASDAS(CRP) LDA, ASAS PR, and ASAS40 at 1 year (Figure 1). In a multivariable analysis, improvement from BL to Week 12 in back pain score consistently predicted several efficacy outcomes at 1 year.Conclusion:In upadacitinib-treated patients with AS, improvement in PROs and reduction in back pain score at 12 weeks predicted clinical outcomes at 1 year.References:[1]van der Heijde D, et al. Lancet 2019;394:2108–17.Figure 1.Association between Week 12 response or back pain at Week 12 and achievement of efficacy outcomes at 1 year (univariable analysis)All ASDAS scores are calculated using C-reactive proteinASDAS CII: change from BL ≥1.1; ASDAS MI: change from BL ≥2.0; MBI back pain: ≥2-point reduction in absolute score and ≥33% reduction from BL on a 0–10 NRSASAS, Assessment of SpondyloArthritis International Society; ASAS40, ≥40% improvement in ASAS criteria; ASDAS, Ankylosing Spondylitis Disease Activity Score; BASDAI50, ≥50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index; BL, baseline; CI, confidence interval; CII, clinically important improvement; ID, inactive disease; LDA, low disease activity; MBI, much better improvement; MI, major improvement; NRS, numeric rating scale; OR, odds ratio; PR, partial remissionAcknowledgements:AbbVie funded this study; contributed to its design; participated in data collection, analysis, and interpretation of the data; and participated in the writing, review, and approval of the abstract. No honoraria or payments were made for authorship. Medical writing support was provided by Laura Chalmers, PhD, of 2 the Nth (Cheshire, UK), and was funded by AbbVie.Disclosure of Interests:Marina Magrey Consultant of: Consultant for Janssen and Novartis; member of advisory boards for Eli Lilly, Janssen, Novartis, and UCB, Grant/research support from: AbbVie, Sofia Ramiro Consultant of: AbbVie, Eli Lilly, MSD, Novartis, Sanofi, and UCB, Grant/research support from: MSD, Marcelo Pinheiro Consultant of: AbbVie, Eli Lilly, Janssen, and Novartis, Tianming Gao Employee of: AbbVie employee and may own stock or options, Fabiana Ganz Employee of: AbbVie employee and may own stock or options, In-Ho Song Employee of: AbbVie employee and may own stock or options, Ana Biljan Employee of: AbbVie employee and may own stock or options, Nigil Haroon Consultant of: AbbVie, Amgen, Eli Lilly, Janssen, MSD, Novartis, Pfizer, and UCB, Martin Rudwaleit Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB


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