Association of Angiogenic and Inflammatory Markers with Power Doppler Ultrasound Vascularity Grade and DAS28-CRP in Early Rheumatoid Arthritis: A Comparative Analysis

Abstract

Objective Upregulation of various proinflammatory and angiogenic mediators orchestrates the typical pathological synovial alterations in rheumatoid arthritis (RA). DAS28-CRP is commonly used for assessment of RA disease activity and power Doppler ultrasonography (PDUS) is an important modality for assessing synovial vascularity. This study was intended to look for the association of various inflammatory and angiogenic mediators, with respect to different PDUS vascularity grades and disease activity status, in early RA patients. Methods 50 early RA patients (<6 months disease duration) with either moderate or high disease activity and 30 healthy controls were included in this study. RA patients were subcategorized based on PDUS vascularity grading of wrist joints. Serum levels of proinflammatory cytokines [tumor necrosis factor-α (TNF- α); interleukin-6(IL-6)] and angiogenic markers [angiopoietin-1 and 2 (Ang-1 and Ang-2); vascular endothelial growth factor (VEGF) ] were measured and compared among different patient subgroups. Results Among 50 patients, 22 and 28 patients had moderate and high DAS28-CRP score, respectively. Patients with grade 3 PDUS score, even with moderate DAS value, showed a significant rise in Ang-1 (p<0.02), VEGF (p<0.008), Ang-2 (p <0.001), and TNF-α (p<0.005) level compared to grade 2 PDUS patients with high DAS values. Conclusion Higher serum level of angiogenic and inflammatory markers was noted among patients with moderate disease activity but with advanced PDUS vascularity (grade 3) in comparison to high disease activity group with less severe PDUS vascularity (grade 2). PDUS vascularity grading better reflects some markers of angiogenesis and inflammation, than composite disease activity index.

Association of Circulating Vascular Endothelial Growth Factor Levels With Autoimmune Diseases: A Systematic Review and Meta-Analysis

“…Among 241 eligible studies meeting the inclusion criteria, 76 articles were excluded due to unextractable data, insufficient data on HCs, irrelevant VEGF sample type (urine/synovial fluid/tear fluid), or inappropriate disease control groups. Finally, 165 studies were included in the meta-analysis, with 28,29,40,13,8,12,16,23, and six studies on SLE (20,21,, RA (12, 22-24, 38, 43, 52-74), SSc (11,38,39,64,, BD (111)(112)(113)(114)(115)(116)(117)(118)(119)(120)(121)(122)(123), KD (18,(124)(125)(126)(127)(128)(129)(130), AS (55,73,(131)(132)(133)(134)(135)(136)(137)(138)(139)(140)…”

“…These findings suggest VEGF as a potential pathogenic factor with promising diagnostic value in ADs. However, no clinical guidelines currently recommend serum VEGF evaluation in routine care and counseling of patients with ADs, and intensive studies are warranted to identify the clinical implications of the findings regarding VEGF's role in ADs to date and to resolve contradictory results (20)(21)(22)(23)(24).…”

Correlation of ultrasonography synovitis with disease activity and clinical response to etanercept treatment in juvenile idiopathic arthritis patients

“…US synovitis also has potential to be used as a disease-monitoring marker in arthritis disease. For instance, a study detected US synovitis of wrist joints in 50 early rheumatoid arthritis patients, and disclosed PD-US synovitis showed positive correlation with TNF-α, IL-6, and angiopoietin-1 and -2 levels (18). Another study used a 7-joint US synovitis score in 50 RA patients, and found that the scores were greatly correlated with disease activity assessed by 3 different composite disease indices (19).…”

Gelenksonografie im Treat-to-Target-Konzept bei der juvenilen idiopathischen Arthritis

“…Ramirez et al konnten zeigen, dass in einer Kohorte von Patienten in klinischer Remission aber mit noch sonografisch nachweisbarer Synovialitis, 45 % (n = 25) der Patienten erhöhte angiogenetische Biomarker ohne Nachweis von proinflammatorischen Zytokinen hatten [27]. Ähnliche Ergebnisse konnten von Misra gezeigt werden: Patienten mit Hypervaskularisation Grad 3 hatten höhere Serumlevel von angiogenetischen Entzündungsmarkern verglichen mit Patienten mit einer milden Power-Doppler-Aktivität Grad 2, obwohl die letztere Gruppe eine hohe klinische Krankheitsaktivität und die erste nur milde Krankheitszeichen aufwies [28]. Die Serum-IL-17-Konzentration korreliert mit Hypervaskularisation in den Kniegelenken bei Früharthritis und weist auf das Potenzial einer frühen Behandlung mit IL-17-Antagonisten hin [29].…”