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- Manojlovic, M., et al.
(författare)
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Microparticles expressing myeloperoxidase as potential biomarkers in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV)
- 2020
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Ingår i: Journal of Molecular Medicine. - : SPRINGER HEIDELBERG. - 0946-2716 .- 1432-1440. ; 98:9, s. 1279-1286
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Tidskriftsartikel (refereegranskat)abstract
- To investigate presence of circulating myeloperoxidase-positive microparticles (MPO(+)MPs) in relation to disease activity in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Forty-six patients with AAV and 23 age- and sex-matched healthy controls were included. Vasculitis disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS). MPs were analyzed in citrate plasma by flow cytometry and phenotyped based on MPO expression and co-expression of pentraxin-3 (PTX3), high mobility group box 1 protein (HMGB1), and tumor necrosis factor-like weak inducer of apoptosis (TWEAK). Serum levels of PTX3, sTWEAK, and HMGB1 were also determined. Twenty-three patients had active vasculitis (BVAS >= 1). Concentrations of MPO(+)MPs expressing PTX3, HMGB1, and TWEAK were significantly higher in patients compared to healthy controls (p< 0.001,p< 0.01,p< 0.001, respectively), while concentrations of PTX3(+)and HMGB1(+)MPO(+)MPs were significantly higher in active AAV compared to patients in remission. MPO(+)MPs expressing either PTX3 or HMGB1 were associated with BVAS (r= 0.5,p< 0.001;r= 0.3,p= 0.04, respectively). Significantly higher serum PTX3 levels were found in active- than in inactive AAV (p< 0.001), correlating strongly with BVAS (r= 0.7,p< 0.001). Serum levels of sTWEAK and HMGB1 did not differ between patients and controls. Concentration of MPO(+)MPs is increased in plasma from AAV patients compared to healthy individuals. PTX3 in serum as well as PTX3 and HMGB1 expressed on MPO(+)MPs were associated with disease activity in the investigated patients. Key messages Myeloperoxidase-positive microparticles (MPO+MPs) are increased in plasma from patients with ANCA-associated vasculitis. Concentrations of MPO+MPs expressing PTX3, HMGB1, and TWEAK were significantly higher in patients compared to healthy controls. MPO+MPs expressing PTX3 and HMGB1 are associated with disease activity in ANCA-associated vasculitis.
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- Circiumaru, A, et al.
(författare)
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SPECIFIC ACPA REACTIVITIES AND INFLAMMATORY BIOMARKERS ALONG WITH ULTRASOUND TENOSYNOVITIS ARE ASSOCIATED WITH ARTHRITIS ONSET IN A POPULATION AT RISK FOR RHEUMATOID ARTHRITIS
- 2020
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 1247-1247
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Anti-citrullinated protein antibodies (ACPA) are characteristic markers for rheumatoid arthritis (RA), developing years before disease onset. Early clinical and biological biomarkers could provide useful information on the onset of RA in predisposed individuals.Objectives:The aim of the study was to investigate whether ACPA along with inflammatory markers and musculoskeletal ultrasound changes could predict arthritis development in individuals at risk for RA.Methods:ACPA-positive individuals with musculoskeletal complaints were referred from primary care to a rheumatology clinic, recruited in the Risk-RA research program and followed-up for up to 3 years, between April 2014 and October 2019. All individuals lacked arthritis both at clinical examination by a trained rheumatologist and ultrasound assessment of hands and feet and any other symptomatic joints (according to EULAR-OMERACT definition). Blood samples were collected at inclusion and were analyzed for 15 ACPA fine specificities (by custom made peptide array), 92 inflammation-associated protein biomarkers (by multiplex immunoassay with Olink extension technology) and HLA-SE (DR low resolution kit). Statistical analysis used univariate and multivariate models with backwards selection and cox regression.Results:268 individuals with a median age of 48 (36-58) were recruited, out of which 212 (79%) were females. 75 (28%) developed arthritis within 11 months of follow-up while the median follow-up for those not developing arthritis was 21 months (14-28). Increased ACPA levels, shorter symptom duration and RF positivity were the main differences between individuals developing arthritis and those who did not. In univariate models, the presence of HLA-SE, specific ACPA reactivities, certain inflammatory markers and ultrasound-detected tenosynovitis were associated with arthritis development. In multivariate analysis the presence of anti-cit-fillagrin (HR 2.1 (95% CI 1.2-3.7, p 0.01), IL6 levels (HR 1.4 (95% CI 1.2-1.7, p 0.0001) and tenosynovitis (HR 2.9 (95% CI 1.7-5.0, p 0.0001) remained significant predictors for arthritis onset.Conclusion:Certain ACPA reactivities together with inflammatory markers and ultrasound-detected tenosynovitis predict arthritis development in predisposed individuals for developing RA.Disclosure of Interests:None declared
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- Jonasdottir, A. D., et al.
(författare)
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Pentraxin-3-a potential biomarker in ANCA-associated vasculitis
- 2023
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Ingår i: Scandinavian Journal of Rheumatology. - : Taylor & Francis Ltd. - 0300-9742 .- 1502-7732. ; 52:3, s. 293-301
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Tidskriftsartikel (refereegranskat)abstract
- Objective The aim of this study was to investigate pentraxin-3 (PTX3) as a potential biomarker of inflammatory activity in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) at baseline and 6 month follow-up in a longitudinal cohort. Method Plasma PTX3 levels were measured in 79 newly diagnosed or relapsing AAV patients at baseline and 6 month follow-up, and in 23 healthy controls. Urinary PTX3 levels were measured in 34 of the patients. C-reactive protein (CRP), creatinine, and albuminuria were measured and the cumulative glucocorticoid dose at inclusion was calculated. The Birmingham Vasculitis Activity Score (BVAS) was assessed at baseline and follow-up. Results Plasma PTX3 levels were significantly higher at baseline than at 6 months (2.85 vs 1.23 ng/mL, p < 0.001). Plasma and urinary PTX3 levels correlated with BVAS at baseline (rho = 0.45, p < 0.001, and rho = 0.49, p = 0.008, respectively). A significant correlation between both plasma and urinary PTX3 levels and estimated glomerular filtration rate and albuminuria was found. However, there was no correlation between plasma and urinary PTX3 levels. At baseline, plasma and urinary PTX3 levels were significantly higher in patients with kidney involvement. PTX3 levels did not correlate with CRP, nor was there a correlation between CRP levels and BVAS at baseline. Conclusion Plasma and urinary PTX3 seem to reflect disease activity in AAV better than the commonly used CRP. PTX3 may have a potential role as a biomarker in monitoring disease activity in AAV patients, particularly in patients with kidney involvement.
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- Juto, A, et al.
(författare)
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MYELOPEROXIDASE (MPO) POSITIVE EXTRACELLULAR VESICLES (EVS) EXPRESSING COMPLEMENT SPLIT PRODUCTS IN ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODY (ANCA)-ASSOCIATED VASCULITIS (AAV)
- 2022
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 1434-1434
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Complement activation has a critical role for the development of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We have previously shown increased expression of complement split products C3a and C5a on myeloperoxidase (MPO) positive EVs (MPO+EVs) in plasma from AAV patients with kidney involvement compared to the patients with non-renal disease and the EV-levels correlated with disease activity (1).ObjectivesTo investigate the expression of a larger set of complement components on circulating MPO+EVs in relation to disease activity and kidney involvement in patients with AAV.MethodsEighty-nine patients with AAV and 23 healthy controls were included. The concentration of MPO+EVs expressing complement split products C3a, C4d, C5a, terminal complement complex-TCC (C5b-9) or complement factor B (CFB) were analyzed from citrate plasma by flow cytometry. The assessment of vasculitis disease activity was performed using the Birmingham Vasculitis Activity Score (BVAS).ResultsIn the AAV group, there were 47 males (52.8%), the median age was 56 years and 33 (37.1%) patients were anti-MPO-positive and 54 (60.7%) were anti-PR3-positive. Two patients were positive for both antibodies. Median disease duration for patients with active AAV (BVAS>0; n=81) was 4 days and for patients in remission (BVAS 0; n=8) 1259 days. 64% had kidney involvement (n=52). Highly active AAV (BVAS ≥12) was noted in 62 patients, of whom 49 patients had kidney involvement. Active disease (0<BVAS<12) was seen in 19 patients. AAV patients had significantly higher levels of MPO+, MPO+C3a+, MPO+C4d+ and MPO+TCC+ EVs compared to healthy controls (all p<0.001). Patients in remission had higher levels of MPO+, MPO+C4d+ and MPO+TCC+ EVs compared to healthy controls (all p≤0.001). There was a significant difference in levels of MPO+(p=0.02), MPO+C3a+(p<0.001), MPO+C4d+(p<0.001) and MPO+TCC+ EVs (p<0.001) in patients with kidney involvement compared with patients without (n=29) (Figure 1). For patients with BVAS>0 there was a weak correlation between MPO+, MPO+C3a+, MPO+C4d+, MPO+TCC+ EVs and BVAS. Kidney biopsies from 34 patients were classified according to histopathological class (2): crescentic (n=6), focal (n=18), mixed (n=6), sclerotic (n=4). The level of MPO+C4d+EVs was higher in the sclerotic type compared to focal (p=0.04, 95% CI [2.4–103.7]) and mixed (p=0.04, 95% CI [1.4–119.1]).ConclusionLevels of EVs expressing complement split products were generally increased in AAV patients and patients with kidney involvement had higher levels of total MPO+EVs exposing C3a, C4d or TCC compared with patients without suggesting a role in kidney AAV pathogenesis. Patients with sclerotic kidney histotype had higher levels of MPO+C4d EVs compared with focal and mixed subgroups pointing to that activation of the classical complement pathway may be of importance in severe forms of kidney AAV.References[1]Antovic A et al. J Rheumatol. 2020 May 1;47(5):714-721. doi: 10.3899/jrheum.181347. Epub 2019 Aug 1. PMID: 31371653.[2]Berden AE et al. J Am Soc Nephrol. 2010 Oct;21(10):1628-36. doi: 10.1681/ASN.2010050477. Epub 2010 Jul 8. PMID: 20616173.Disclosure of InterestsNone declared
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- Kisten, Y, et al.
(författare)
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TENOSYNOVITIS, SYNOVIAL HYPERTROPHY AND FEET BURSITIS ARE USEFUL ULTRASOUND BIOMARKERS FOR PREDICTING ARTHRITIS DEVELOPMENT IN A POPULATION AT-RISK FOR RHEUMATOID ARTHRITIS
- 2021
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 87-87
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Musculoskeletal ultrasound (MSUS) evaluation of individuals at risk for developing rheumatoid arthritis (RA) having Anti-Citrullinated Protein Antibody (ACPA) positivity and musculoskeletal complaints, may play an important role in the very early detection of RA.Objectives:We aimed to identify which ultrasound markers could predict arthritis development.Methods:Individuals with musculoskeletal complaints with a positive anti-CCP2 test were referred to the rheumatology department for a detailed clinical (68 joint count) and MSUS examination of the hands, feet and any symptomatic joints. Only those without clinical and/or MSUS detected arthritis were included in the RISK RA prospective cohort and followed-up over 3 years/ or until arthritis onset. Using EULAR-OMERACT guidelines1, MSUS markers for synovial hypertrophy (SH) and hyperemia (Doppler activity) were documented for each visit. Finger and wrist tendons were screened for any signs of tenosynovitis (TS), and between metatarsal joints for bursitis. Association of MSUS biomarkers with arthritis development was tested (comparing proportions) using Chi-Squared or Fisher’s exact tests.Results:288 individuals were included from January 2014 to October 2019 (79% female, 35% RF positive, median age 48 years: IQR: 36-58). Within a median of 38 months (IQR: 1-72) since recruitment, 84 individuals (28%) developed an arthritis diagnosis.Prior to obtaining any diagnosis (at inclusion and/or follow-up visit), 95 of the 288 individuals (33%) had at least one type of MSUS anatomical modification present (around the tendons, joint synovium and/or within bursal cavities), and 56% (53/95) of these individuals eventually developed arthritis. Of the remaining 193 that did not present with any obvious MSUS changes, 16% progressed towards arthritis development.The presence of tenosynovitis was detected in 64 of 288 individuals scanned prior to diagnosis and were more frequent in those developing arthritis (44%, 37/84) as compared to those with TS not developing arthritis (13%, 27/204), p<0.0001. The extensor carpi ulnaris wrist tendons were mostly involved. Sonographic changes within the synovium were noted in 11% (32/288) of all individuals, mostly affecting the metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joints. There was a higher incidence of synovial hypertrophy detected in those developing arthritis (22%, 18/24), as compared to those that remained arthritis free (7%, 14/204), p<0.0001. The MCP joints with synovial hypertrophy were more prone to arthritis development as compared to the MTP’s. Furthermore, we observed a higher frequency of bursitis between the MTP joints in individuals developing arthritis, as compared to individuals having a bursitis who did not develop arthritis (13%, 11/84 versus 7%, 14/204, p=0.009).Conclusion:Ultrasound biomarkers such as tenosynovitis of the extensor carpi ulnaris, synovial hypertrophy of the MCP joints and feet bursitis have good potential to predict arthritis development in a population at-risk for rheumatoid arthritis.References:[1]Maria-Antonietta D’Agostino et al. RMD Open 2017;3:e 000428Acknowledgements:All study participants and patients, including researchers that are part of the multidisciplinary laboratory, clinical and academic teams of the RISK RA study group, as well as all assisting this research in one form or the other are greatly acknowledged.Disclosure of Interests:None declared
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