Role of plasma fibrinogen in assessing disease activity of patients with gout

Background:In the management of chronic arthritis, such as Rheumatoid Arthritis (RA), Ultrasound (US) assessment can provide relevant information about the joint inflammatory status in the diagnostic phase and even more in the monitoring of disease activity and structural damage1,2.Objectives:In this longitudinal study, we aimed to assesse the role of US in predicting the efficacy of JAK-inhibitors (JAKi) in RA patients.Methods:We enrolled RA patients starting baricitinib or tofacitinib. All patients were evaluated at baseline and after 4, 12, 24, 48 weeks. Disease activity was calculated by DAS28CRP. US examination in 22 joints (I–V MCPs and PIPs, wrists) aimed at evaluating inflammatory features (synovial effusion and hypertrophy, power Doppler-PD), through a semi-quantitative scale (0-3). The total US (0-198) and PD (0-66) scores were calculated. We scanned bilateral flexor (I–V fingers of hands) and extensor compartments (1-6) tendons: tenosynovitis was scored as absent/present (0/1), resulting in a total score (0-22).Results:We studied 102 patients (M/F 15/87; median age 59.2 years, IQR 17.75; median disease duration 144 months, IQR 126), 61 treated with baricitinib and 41 with tofacitinib. At baseline, the median total US score was 18 (IQR 19) and the median PD score 2 (4). We observed a significant reduction in both total and PD US scores at all time-points (p<0.0001) (Figure 1). At baseline, 75.4% of patients showed tenosynovitis involving at least one tendon, with a median score of 2 (IQR 3.5) significantly decreasing after 24 weeks (p=0.02). Multivariate analysis, adjusted for baseline DAS28CRP and other concomitant treatments (including glucocorticoids and methotrexate treatment), confirmed the independent association between baseline US (PD and tenosynovitis) scores and the reduction of disease activity at follow-up evaluations.Conclusion:The present study confirmed the early efficacy of JAKi in RA patients by using US evaluation. Furthermore, power doppler and tenosynovitis scores could play a predictive role in response to treatment.References:[1]MUELLER RB, HASLER C, POPP F, et al. Effectiveness, Tolerability, and Safety of Tofacitinib in Rheumatoid Arthritis: A Retrospective Analysis of Real-World Data from the St. Gallen and Aarau Cohorts. J Clin Med. 2019;8(10):1548.[2]COLEBATCH AN, EDWARDS CJ, ØSTERGAARD M, et al. EULAR recommendations for the use of imaging of the joints in the clinical management of rheumatoid arthritis. Ann Rheum Dis. 2013;72(6):804-14.Figure 1.Ultrasound inflammatory score (a) and Ultrasound Power Doppler (PD) score (b) at baseline and follow-up.Table 1.Baseline characteristics of 414 RA patients.WEEKS04122448US inflammatory score18 (19)11 (15.5)9.5 (11.7)7.5 (8)6 (11)US PD score2 (4)0 (2)0 (1)0 (1)0 (0.7)Disclosure of Interests:Cristina Garufi: None declared, Fulvia Ceccarelli: None declared, Francesca Romana Spinelli Speakers bureau: Abbvie, Eli Lilly, Consultant of: Gilead/Galapagos, Eli Lilly, Grant/research support from: Pfizer, Silvia Mancuso: None declared, Carmelo Pirone: None declared, Fabrizio Conti Speakers bureau: Abbvie, Eli Lilly, Sanofi, Pfizer, Consultant of: Gilead/Galapagos

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OP0045 NLRP12 INVOLVES IN THE LUPUS WITH POSITIVE INTERFERON SIGNATURE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.4215 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 23.2-24

Author(s):

Y. P. Tsao ◽

F. Y. Tseng ◽

C. W. Chao ◽

M. H. Chen ◽

S. T. Chen

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Animal Models ◽

Nucleic Acids ◽

Disease Activity ◽

Interferon Signature ◽

Healthy Donors ◽

Healthy Control ◽

Lupus Disease Activity

Background:Systemic lupus erythematous (SLE) is a systemic autoimmune disease with diverse etiological factors. It was recognized that interferon (IFN) signature involved in the progress of SLE. NLRP12 (NOD-like receptor family (NLR) pyrin domain containing 12) is a pyrin containing NLR protein that we had linked its new biological function to the cross-regulation of Toll like receptor (TLRs) and Rig-I like receptor (RIG-I) pathways. NLPR12 acts as an innate immune check-point in regulating type I IFNs expression during TLRs and RIG-I activation. The importance of NLRP12 in lupus disease activity remained to be elucidated.Objectives:To clarify the role of NLRP12 in regulating the interferon signature.Methods:Peripheral blood mononuclear cells (PBMCs) were collected from SLE patients and healthy donors for analysis of NLRP12 and IFN-α gene expression by RT-QPCR. PBMCs were applied for Chromatin immuneprecipitation (ChIP) assay and electrical mobility shift assay (EMSA) to determine the putative transcription factor that regulates NLRP12 expression. An involvement of epigenetic regulation of NLRP12 expression in SLE patients was also analyzed. Bone marrow derived dendritic cells (BMDCs) were collected from wild type mouse and Nlrp12 knocked-out mice. Another CD14+ monocytes were isolated from 10 cases of lupus patients and 8 cases of healthy control, following by stimulating different type of nucleic acids, and IFN-α and IL-6 were measured with ELISA assay. CD14+ monocytes in lupus patients were also pre-treated with IFNAR2 antibody for further nucleic acid stimulation. Two mice models were applied for evaluation the role of Nlrp12: intraperitoneal injection of TMPD (2,6,10,14-tetramethylpentadecane, or pristane) in C57BL/6 mice and Faslpr mice. Both models were conducted with and without Nlrp12 knockout.Results:NLRP12 expression was significantly lower in PBMC isolated from SLE patients compared to healthy donors. The inverse correlation was observed in NLRP12 and IFNA gene expression as well as NLRP12 expression and amount of double-stranded DNA autoantibody in SLE patients. NLRP12 expression showed negative correlations with IFN-α treatment, as well as herpes simplex virus-1 (HSV-1) infection. Results from ChIP and EMSA analysis indicated a potential transcription factor 1 (TF-1) regulating NLRP12 promoter activity. TF-1 lead to transcriptional suppression of NLRP12 in SLE PBMC, and it was gradually induced after IFN treatment. Recruitment of TF-1 to NLRP12 promoter in SLE PBMC compared to the healthy PBMC was detected, and increased when treating with IFN. Human CD14+ monocytes collected from lupus and healthy control stimulating with different type of nucleic acids revealing significant increasing level of IFN-α and IL-6 in lupus patients. Among animal models, both pristine induced mice and Faslpr mice revealed increasing autoantibodies production and severity of glomerulonephritis in Nlrp12-/- group in comparison with Nlrp12+/+ ones, indicating the role of NLRP12 in maintaining positive interferon signature as well as disease activity.Conclusion:Expression level of NLRP1.2 has been demonstrated to be a biomarker of disease activity in SLE patients. The NLRP12 was involved in the interferon signature, which was also negatively regulated by TF-1. Both clinical samples and animal models revealed NLRP12 in maintaining the positive interferon signature, indicating the possible role of exacerbating factor for lupus disease activity.Disclosure of Interests:None declared

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Psychological Correlates of Self-reported Disease Activity in Ankylosing Spondylitis

The Journal of Rheumatology ◽

10.3899/jrheum.090476 ◽

2010 ◽

Vol 37 (4) ◽

pp. 829-834 ◽

Cited By ~ 29

Author(s):

TAMAR F. BRIONEZ ◽

SHERVIN ASSASSI ◽

JOHN D. REVEILLE ◽

CHARLES GREEN ◽

THOMAS LEARCH ◽

...

Keyword(s):

New York ◽

Ankylosing Spondylitis ◽

Disease Activity ◽

Activity Index ◽

Disease Activity Index ◽

Multivariate Regression Analysis ◽

Passive Coping ◽

Psychological Variables ◽

Psychological Measures

Objective.To investigate the role of psychological variables in self-reported disease activity in patients with ankylosing spondylitis (AS), while controlling for demographic and medical variables.Methods.Patients with AS (n = 294) meeting modified New York criteria completed psychological measures evaluating depression, resilience, active and passive coping, internality, and helplessness. Demographic, clinical, and radiologic data were also collected. Univariate and multivariate analyses were completed to determine the strength of the correlation of psychological variables with disease activity, as measured by the Bath AS Disease Activity Index (BASDAI).Results.In the multivariate regression analysis, the psychological variables contributed significantly to the variance in BASDAI scores, adding an additional 33% to the overall R-square beyond that accounted for by demographic and medical variables (combined R-square 18%). Specifically, arthritis helplessness and depression accounted for the most significant portion of the variance in BASDAI scores in the final model.Conclusion.Arthritis helplessness and depression accounted for significant variability in self-reported disease activity beyond clinical and demographic variables in patients with AS. These findings have important clinical implications in the treatment and monitoring of disease activity in AS, and suggest potential avenues of intervention.

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AB0060 INCREASED AGE/AUTOIMMUNE-ASSOCIATED B CELLS IN RA AND CLINICAL IMPLICATIONS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3026 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1061.3-1061

Author(s):

Y. Qin ◽

Z. Chen

Keyword(s):

B Cells ◽

Disease Activity ◽

Inflammatory Cell ◽

Cell Subset ◽

Disease Status ◽

Low Disease Activity ◽

Rheumatoid Arthritis Joint ◽

Healthy Control ◽

Synovial Tissues

Background:Age/Autoimmune-associated B cells (ABCs) are an emerging B cell subset that accumulate in aged and autoimmune-prone mice. Expansion of human ABCs has been observed in patients with autoimmune diseases like SLE and correlated with disease activity. However, it is less known whether ABCs contribute to the pathogenesis of RA.Objectives:The aim of this work was to explore the role of ABCs in RA.Methods:83 RA patients who met the 2010 ACR classification criteria for RA, 42 sex and age matched healthy control (HC), 35 Spondyloarthritis (SpA) and 31 Osteoarthritis (OA) patients were enrolled and blood samples were collected. The proportion of circulating ABCs was detected by flow cytometry and association with clinical and laboratory parameters were analyzed. Expression of characteristic proteins and inflammatory cytokines on ABCs were examined by quantitative real-time PCR.Results:The proportion of ABCs, defined as CD19+CD27-IgD-CD21-CD11c+, was significantly elevated in RA patients, compared with HC, SpA and OA patients. The frequency of ABCs was higher in patients with high disease activity (DAS28>3.2) compared with remission and low disease activity (DAS28<3.2). There was a positive correlation of ABCs with SJC, TJC, DAS28 whereas no association with RF and anti-CCP titer were observed. In addition, increased mRNA expression levels of T-bet, IL-21, MAF and IL-17 were noted on ABCs compared with CD19+CD27-CD11c- B cells.Conclusion:ABCs were expanded in RA patients and associated with active disease status. It might contribute to RA development by production of IL-17.References:[1]Cancro, M.P., Age-Associated B Cells. Annu Rev Immunol, 2020. 38(315-340).[2]F. Zhang, K. Wei, K. Slowikowski et al., Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry. Nat Immunol 2019, 20, 928-942.Disclosure of Interests:None declared

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