scholarly journals Associations of ultrasound-based inflammation patterns with peripheral innate lymphoid cell populations, serum cytokines/chemokines, and treatment response to methotrexate in rheumatoid arthritis and spondyloarthritis

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0252116
Author(s):  
Manami Kato ◽  
Kei Ikeda ◽  
Takahiro Sugiyama ◽  
Shigeru Tanaka ◽  
Kazuma Iida ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Treatment Response ◽  
Peripheral Blood ◽  
Lymphoid Cell ◽  
Power Doppler ◽  
Serum Levels ◽  
Dominant Group ◽  
Innate Lymphoid Cell ◽  
Acr20 Response ◽  
Serum Cytokines

Objectives We aimed to explore the associations of musculoskeletal inflammation patterns with peripheral blood innate lymphoid cell (ILC) populations, serum cytokines/chemokines, and treatment response to methotrexate in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). Methods We enrolled 100 patients with either RA or SpA and performed ultrasound to evaluate power Doppler signals for synovitis (52 joint regions), tenosynovitis (20 tendons), and enthesitis (44 sites). We performed clustering analysis using unsupervised random forest based on the multi-axis ultrasound information and classified the patients into groups. We identified and counted ILC1-3 populations in the peripheral blood by flow cytometry and also measured the serum levels of 20 cytokines/chemokines. We also determined ACR20 response at 3 months in 38 patients who began treatment with methotrexate after study assessment. Results Synovitis was more prevalent and severe in RA than in SpA, whereas tenosynovitis and enthesitis were comparable between RA and SpA. Patients were classified into two groups which represented synovitis-dominant and synovitis-nondominant inflammation patterns. While peripheral ILC counts were not significantly different between RA and SpA, they were significantly higher in the synovitis-nondominant group than in the synovitis-dominant group (ILC1-3: p = 0.0007, p = 0.0061, and p = 0.0002, respectively). On the other hand, clustering of patients based on serum cytokines/chemokines did not clearly correspond either to clinical diagnoses or to synovitis-dominant/nondominant patterns. The synovitis-dominant pattern was the most significant factor that predicted clinical response to methotrexate (p = 0.0065). Conclusions Musculoskeletal inflammation patterns determined by ultrasound are associated with peripheral ILC counts and could predict treatment response to methotrexate.

scholarly journals Associations of ultrasound-based inflammation patterns with peripheral innate lymphoid cell populations, serum cytokine/chemokines, and treatment response to methotrexate in rheumatoid arthritis and spondyloarthritis

2020 ◽  
Author(s):  
Manami Kato ◽  
Kei Ikeda ◽  
Takahiro Sugiyama ◽  
Shigeru Tanaka ◽  
Kazuma Iida ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Treatment Response ◽  
Peripheral Blood ◽  
Lymphoid Cell ◽  
Power Doppler ◽  
Serum Cytokine ◽  
Dominant Group ◽  
Innate Lymphoid Cell ◽  
Clinical Trial Registry ◽  
Acr20 Response

Abstract Background: We aimed to clarify the associations of musculoskeletal inflammation patterns with peripheral blood innate lymphoid cell (ILC) populations, serum cytokine/chemokines, and treatment response to methotrexate in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA).Methods: We enrolled patients with either RA or SpA who had peripheral symptoms and performed comprehensive ultrasound to evaluate power Doppler signals for synovitis (52 joint regions), tenosynovitis (20 tendons), and enthesitis (44 sites). We performed clustering analysis using unsupervised random forest based on the multi-axis ultrasound information and classified the patients into groups. We identified and counted ILC1-3 populations in the peripheral blood by flow cytometry and also measured the serum levels of 20 cytokine/chemokines. We also determined the American College of Rheumatology 20% improvement (ACR20) response at 3 months in 38 patients who initiated treatment with methotrexate after baseline assessment. Results: We enrolled a total of 100 patients with RA (n=66) or SpA (n=34). Synovitis was more prevalent and severer in RA than in SpA, whereas tenosynovitis and enthesitis were comparable between RA and SpA. Patients were classified into two groups which represented synovitis-dominant and synovitis-nondominant inflammation patterns, respectively. While peripheral ILC counts were not significantly different between RA and SpA, they were significantly higher in the synovitis-nondominant group than in the synovitis-dominant group (ILC1-3 p=0.0007, p=0.0061, p=0.0002, respectively). On the other hand, clustering of patients based on serum cytokine/chemokines did not clearly correspond either to clinical diagnoses or to synovitis-dominant/nondominant patterns. The synovitis-nondominant pattern was the factor that predicted no clinical response to methotrexate most significantly (p=0.0065).Conclusions: Ultrasound-detected musculoskeletal inflammation is clustered into synovitis-dominant and nondominant patterns. These patterns are associated with peripheral ILC counts and could predict treatment response to methotrexate. These data suggest that ultrasound-based inflammation patterns can be utilized to establish more individualized treatment for both RA and SpA. Trial registration: The study has been registered in UMIN Clinical Trial Registry (UMIN ID: 000033797, date of registration: 18th of August, 2018).

scholarly journals Tofacitinib Suppresses Several JAK-STAT Pathways in Rheumatoid Arthritis In Vivo and Baseline Signaling Profile Associates With Treatment Response

2021 ◽  
Vol 12 ◽  
Author(s):  
Maaria Palmroth ◽  
Krista Kuuliala ◽  
Ritva Peltomaa ◽  
Anniina Virtanen ◽  
Antti Kuuliala ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Treatment Response ◽  
Peripheral Blood ◽  
Janus Kinase ◽  
Cytokine Signaling ◽  
Stat3 Phosphorylation ◽  
Stat Pathway

ObjectiveCurrent knowledge on the actions of tofacitinib on cytokine signaling pathways in rheumatoid arthritis (RA) is based on in vitro studies. Our study is the first to examine the effects of tofacitinib treatment on Janus kinase (JAK) - signal transducer and activator of transcription (STAT) pathways in vivo in patients with RA.MethodsSixteen patients with active RA, despite treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), received tofacitinib 5 mg twice daily for three months. Levels of constitutive and cytokine-induced phosphorylated STATs in peripheral blood monocytes, T cells and B cells were measured by flow cytometry at baseline and three-month visits. mRNA expression of JAKs, STATs and suppressors of cytokine signaling (SOCS) were measured from peripheral blood mononuclear cells (PBMCs) by quantitative PCR. Association of baseline signaling profile with treatment response was also investigated.ResultsTofacitinib, in csDMARDs background, decreased median disease activity score (DAS28) from 4.4 to 2.6 (p < 0.001). Tofacitinib treatment significantly decreased cytokine-induced phosphorylation of all JAK-STAT pathways studied. However, the magnitude of the inhibitory effect depended on the cytokine and cell type studied, varying from 10% to 73% inhibition following 3-month treatment with tofacitinib. In general, strongest inhibition by tofacitinib was observed with STAT phosphorylations induced by cytokines signaling through the common-γ-chain cytokine receptor in T cells, while lowest inhibition was demonstrated for IL-10 -induced STAT3 phosphorylation in monocytes. Constitutive STAT1, STAT3, STAT4 and STAT5 phosphorylation in monocytes and/or T cells was also downregulated by tofacitinib. Tofacitinib treatment downregulated the expression of several JAK-STAT pathway components in PBMCs, SOCSs showing the strongest downregulation. Baseline STAT phosphorylation levels in T cells and monocytes and SOCS3 expression in PBMCs correlated with treatment response.ConclusionsTofacitinib suppresses multiple JAK-STAT pathways in cytokine and cell population specific manner in RA patients in vivo. Besides directly inhibiting JAK activation, tofacitinib downregulates the expression of JAK-STAT pathway components. This may modulate the effects of tofacitinib on JAK-STAT pathway activation in vivo and explain some of the differential findings between the current study and previous in vitro studies. Finally, baseline immunological markers associate with the treatment response to tofacitinib.

scholarly journals Can Rheumatoid factor and Anti-cyclic citrullinated peptides predict true remission in rheumatoid arthritis patients? Study of relationship between autoantibodies levels and muskuloskelatal ultrasound findings in a sample cohort of Egyptian patients in clinical remission

2021 ◽  
Author(s):  
Eman Hassan Al Sayed ◽  
Doaa Shaker Amin
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Rheumatoid Factor ◽  
Clinical Remission ◽  
Power Doppler ◽  
Serum Levels ◽  
Cross Sectional Study ◽  
University Hospital ◽  
Gray Scale ◽  
Cross Sectional

Abstract BackgroundTrue remission is the ultimate goal for rheumatoid arthritis (RA) therapy. Our aim was to investigate the relationship between serum levels of rheumatoid factor (RF) and anti-cyclic citrullinated peptides (Anti-CCP) and ultrasonographic (US) findings in Egyptian RA patients in clinical remission.MethodsUsing data from a cross-sectional study on 50 RA patients in clinical remission or low disease activity (LDA) as defined by disease activity score (DAS28-ESR) cutoff points, performed in Alexandria University Hospital; we analyzed statistical relationships and correlations between RF, Anti-CCP) and Gray Scale (GS) and Power Doppler (PD) US using US7 score. US remission was defined as on a GS ≤ 1 and PD = 0. ResultsAmong 34 patients in clinical remission, 61.8% (21) of patients in clinical remission were in ultrasonographic remission, and 38.2% (13) of patients in clinical remission had subclinical ultrasonographic activity. Patients in clinical remission with US remission had significantly higher Anti-CCP (p= 0.006) but not RF (p= 0.086), than those in clinical remission with US subclinical activity. Anti-CCP positively correlated with synovitis score by power Doppler US (PDUS) (rs= 0.553, p= 0.001), and tenosynovitis/paratenonitis score by gray scale US(GSUS) (rs=0.389, p= 0.023).ConclusionWe demonstrated that patients in clinical RA remission with subclinical US activity had higher serum levels of Anti-CCP, but not RF. Such an association should guide further treatment decisions for those patients.

SAT0086 Leptin and adiponectin serum levels as predictors of treatment response in patients with rheumatoid arthritis

2013 ◽  
Vol 71 (Suppl 3) ◽  
pp. 499.1-499 ◽  
Author(s):  
D.X. Xibille ◽  
S.E. Hernández Gόngora ◽  
M. Sandoval Rios ◽  
J.E. Ortíz Panozo ◽  
C. Bustos Rivera Bahena ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Treatment Response ◽  
Serum Levels

Musculoskeletal ultrasound using superb microvascular imaging documents treatment response to biosimilar infliximab in rheumatoid arthritis

2021 ◽  
Vol 14 (2) ◽  
pp. e239112
Author(s):  
Julian Alejandro Santos ◽  
Cherica Afurong Tee ◽  
Romelito Jose Galvan Galsim ◽  
Michael Lucas Tee
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Treatment Response ◽  
Activity Index ◽  
Power Doppler ◽  
Musculoskeletal Ultrasound ◽  
Joint Effusion ◽  
Das 28 ◽  
Superb Microvascular Imaging ◽  
Microvascular Imaging

A 60-year-old woman with rheumatoid arthritis consulted for acute flare. She had elevated disease activity score 28 - erythrocyte sedimentation rate (DAS 28-ESR) of 6.88 and clinical disease activity index (CDAI) of 32. Her 12-joint ultrasound revealed widespread joint effusion. Synovial vascularity scores measured through superb microvascular imaging (SMI) and power Doppler were universally increased. We documented her treatment response 2 weeks after she received a single dose of biosimilar infliximab using clinical and sonographic data. Her DAS 28-ESR and CDAI scores decreased to 4.21 and 7.0, respectively. Reduction in synovial vascularity scores was demonstrated using SMI. While there was near total resolution in joint effusion and tenosynovitis, SMI was able to demonstrate synovial vascularity in joints with no clinical swelling nor tenderness. Musculoskeletal ultrasound and superb microvascular imaging are useful adjuncts in evaluating synovitis in rheumatoid arthritis and documenting treatment response through documentation of synovial vascularity, effusion and tenosynovitis.

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