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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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- 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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- Chatzidionysiou, K, et al.
(författare)
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Tocilizumab decreases T cells but not macrophages in the synovium of patients with rheumatoid arthritis while it increases the levels of serum interleukin-6 and RANKL
- 2021
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Ingår i: RMD open. - : BMJ. - 2056-5933. ; 7:2
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Tidskriftsartikel (refereegranskat)abstract
- Our knowledge about the effect of tocilizumab (TCZ) on the synovium in rheumatoid arthritis (RA) is limited. The aim of this study was to investigate the effect of TCZ on citrullination and on inflammation in the synovial tissue and in the peripheral blood.Methods15 patients with RA underwent synovial biopsy before and 8 weeks after TCZ initiation. Clinical evaluation was performed at baseline and at 8 weeks. Using immunohistochemistry, we evaluated the expression of CD68, CD3, CD20, osteoprotegerin (OPG) and receptor activator for nuclear factor-κB ligand (RANKL) before and after treatment with TCZ. We also analysed the expression of protein arginine deiminase (PAD)-2 and PAD-4 enzymes in the synovial tissue and protein citrullination patterns with the help of anticitrullinated protein antibody (ACPA) clones 1325:04C03 and 1325:01B09. Serum levels of interleukin-6 (IL-6), IL-8, RANKL, OPG and C-terminal crosslinked telopeptide type II collagen were measured by ELISA. Paired-wise Wilcoxon signed-rank test was used to compare median values before and after treatment.ResultsDisease activity in patients was reduced from baseline to 8 weeks. Although PAD-2 and PAD-4 expressions remained unchanged after TCZ treatment, the binding of one ACPA clone decreased in the synovial tissue. TCZ did not affect the number of CD68+ macrophages or CD20+ B cells but induced significant decrease in the number of CD3+ T cells. RANKL and OPG expression remained unchanged in the synovial tissue. A significant increase in the levels of IL-6 and RANKL was observed in the serum. This increase was statistically significant in patients who responded to TCZ (achieving Clinical Disease Activity Index low disease activity or remission) but not in non-responders.ConclusionsTCZ reduced synovial T-cell counts but not macrophages. A significant increase of serum IL-6 was observed in responders.
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