Synovial Biopsy Research Articles

Infiltrations of plasma cells in synovium predict inadequate response to Adalimumab in Rheumatoid Arthritis patients

ObjectiveRheumatoid arthritis (RA) is a clinically heterogeneous and complex autoimmune disease, making the prediction of therapeutic responses a significant challenge. This study aims to assess the role of clinical and synovial biomarkers in predicting poor response to adalimumab treatment in RA patients.MethodsThis single-center prospective study included 56 RA patients who had an inadequate response to methotrexate (MTX). At baseline, comprehensive assessments including complete blood count, liver and kidney function tests, blood glucose levels, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-citrullinated protein antibody (ACPA), as well as counts of swollen and tender joints, Health Assessment Questionnaire (HAQ) score, pain visual analogue scale (VAS) scores, and DAS28-CRP scores were conducted. Synovial biopsies were performed, followed by an efficacy evaluation at 12 weeks of adalimumab treatment. Patients not meeting the ACR20 criteria were classified into the non-responder group, with the remainder categorized as the responder group.ResultsOut of the participants, 24 (42.9%) failed to achieve ACR20 with adalimumab treatment. Non-responders exhibited higher infiltration of plasma cells in the synovium. Multivariate logistic regression analysis identified the presence of plasma cells as an independent risk factor for inadequate response to adalimumab.ConclusionInadequate responses to adalimumab in RA patients were associated with increased plasma cell infiltrations in the synovium. These findings suggest a promising target for tailored therapies in rheumatoid arthritis.

Synoviocyte detachment: an overlooked yet crucial histological aspect in rheumatoid arthritis

ObjectiveRheumatoid arthritis (RA) is a prevalent autoimmune disorder that leads to chronic joint inflammation, deformity, disability, and systemic complications. This study aimed to analyze the clinical characteristics and synovial pathology of RA patients with synoviocyte detachment, and explore the factors associated with this phenomenon.MethodsThis was a retrospective cohort study included RA patients who underwent synovial biopsy at our center from April to September 2023. Demographic, clinical, laboratory, and synovial histological data were retrospectively collected from medical records at the time of joint synovial biopsy in patients. Microscopic examination of hematoxylin and eosin (HE)-stained synovial tissue sections categorized the samples into synoviocyte detachment and no-synoviocyte detachment groups. Clinical characteristics and synovial pathological changes were compared between the two groups, and the factors associated with synoviocyte detachment were explored through logistic regression analysis.ResultsFifty-five RA patients were enrolled; 45 were females, and the mean age was 53.4 ± 11.8 years. Nine RA patients exhibited synoviocyte detachment. A total of 46 RA patients in the no-synoviocyte detachment group (15 with a normal lining layer and 31 with synovial cell proliferation) were included. Compared with the no-synoviocyte detachment group, the synoviocyte detachment group presented higher RF, ESR, CRP and DAS28-CRP levels (P < 0.05). The synoviocyte detachment group exhibited more prominent neovascularization (P < 0.05). ESR, DAS28-CRP and synovial neovascularization were risk factors associated with synoviocyte detachment in RA patients.ConclusionRA patients with synoviocyte detachment exhibit elevated clinical disease activity, marked by pronounced synovial pathology featuring increased neovascularization and less inflammatory cell infiltration. A significant reduction in lymphocyte count compared with patients with synovial cell proliferation was also observed.

RNA-seq Based Transcriptome Analysis Reveals Role of Myoglobin in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease which manifests as joint destruction and bone erosion, could be caused by both genetic and environmental factors. Currently, the causes of RA are unknown, and targeted therapies are often associated with side effects and contraindications. The detection rate of RA in women is higher than men (3:1), however, there is still a lack of comprehensive understanding of the relationship between sex and RA. We hypothesized gender differences in RA prevalence and their associated mechanisms by performing genome-wide transcriptome analysis of synovial biopsy samples. The results indicated that myoglobin (MB) was differentially expressed between males and females, with higher expression in males than females in healthy populations, while the opposite was observed in RA patients. MB interacted with HLA class II histocompatibility antigen, DM beta (HLA-DMB) and the inflammatory factor interleukin 6 (IL-6) in the human synovial cell line MH7A.

Amyloidosis and carpal tunnel syndrome: can we predict occurrence?

IntroductionCarpal tunnel syndrome, especially when bilateral, may be associated with amyloid deposits, a precursor of systemic amyloidosis. Systemic amyloidosis affects various organs, cardiac involvement having the poorest prognosis. Diagnosis is often delayed. Current treatments are only effective in the early stages of the disease. The primary objective of our study was to evaluate the incidence of amyloidosis in patients with bilateral carpal tunnel syndrome; the secondary aim was to screen for cardiac forms. Material and methodsBetween 2019 and 2023, we conducted a single-center prospective observational and diagnostic study to investigate the anatomical pathology of amyloid deposits in tenosynovial samples taken during open nerve release surgery on the median nerve. The tenosynovial biopsy was sent to a specific laboratory for analysis, and typing if positive. If amyloidosis was detected, the patient was referred to a specialist for a specific work-up. ResultsWe included 54 patients, with a mean age of 67 years (range, 51-89 years): 16 men and 38 women. Sixteen analyses were positive, 12 of which were transthyretin and 4 non-typed. Discussion/conclusionBilateral carpal tunnel syndrome was predictive of amyloidosis. As synovial biopsy during surgery is simple and rapid, it should be implemented to identify amyloidosis at an early stage. This could change prognosis, by improving survival through screening and initiation of early specific treatment. Level of evidenceIV.

Diagnostic Accuracy of Pre-operative Percutaneous Synovial Biopsy and Aspirate Compared with Open Biopsy for Prosthetic Shoulder Infections

BackgroundShoulder arthroplasty revision is associated with a high prevalence of prosthetic infection, and diagnosis remains difficult. The primary aim of the study was to determine the diagnostic accuracy of percutaneous synovial biopsy (PSB) and joint aspiration compared with open culture results in detecting infection in revision shoulder arthroplasty. The second aim was to determine whether biopsy location within the shoulder was associated with culture status. MethodsThis was a multicenter prospective cohort study involving four sites and 69 patients undergoing revision shoulder arthroplasty. The cohort was 57% female with a mean age of 64 years. Preoperative fluoroscopic-guided PSB’s and aspirates were carried out by a musculoskeletal radiologist prior to revision shoulder arthroplasty. The original prostheses consisted of hemiarthroplasties, total shoulder arthroplasties (TSA), resurfacing TSA, reverse shoulder arthroplasties (RSA), and antibiotic spacers. Six synovial tissue biopsies from separate regions in the shoulder were obtained both preoperatively and intra-operatively. The shoulder joint was aspirated, and synovial fluid collected, if available. Infection was considered positive in the setting of two or more matching positive cultures. The PSB cultures were considered “true positive” if the PSB cultures matched the open biopsy cultures. ResultsNineteen percent had positive infection based on PSB and 23% had confirmed culture positive infections based on intra-operative biopsy. The diagnostic accuracy of PSB compared with open biopsy was as follows: sensitivity 0.37 (95% CI 0.13-0.61), specificity 0.81 (95% CI 0.7-0.91), positive predictive value 0.37 (95% CI 0.13 – 0.61), negative predictive value 0.81 (95% CI 0.70-0.91), positive likelihood ratio 1.98 and negative likelihood ratio 0.77. Of the 71 patients, aspiration yielded synovial fluid in 33 patients. Preoperative aspirates detected no infections confirmed positive by open biopsy and correctly identified 81% of absent infections. The diagnostic accuracy of aspirates compared with open biopsy was as follows: sensitivity 0%, specificity 0.81 (95% CI 0.66-0.96), positive predictive value 0%, negative predictive value 0.78 (95% CI 0.63-0.93). Biopsy location within the shoulder was not associated with infection status. DiscussionPreoperative aspiration detected none of the infections proven positive via open biopsy. Although PSB was superior to synovial fluid aspirate, poor likelihood ratios suggests that PSB is not useful as an isolated test in the preoperative workup of the potentially infected patient.Biopsy location was not associated with culture status suggesting that the capsule is uniformly infected, and the location of tissue biopsies does not appear to matter.

Histological synovitis score in juvenile idiopathic arthritis and other pediatric synovial inflammatory conditions

ObjectiveThe Krenn’s scoring is a system for histopathological grading of synovial inflammation, and in adults, useful in etiological grouping. The score has only rarely been used in pediatric samples. We aimed to assess the performance of the score in juvenile idiopathic arthritis and other pediatric synovial inflammatory processes in categorization of the disease and in finding characteristic pathological features. DesignWe collected an unselected series of pediatric (age < 16 years) routine synovial biopsy samples to represent normal synovium and inflammatory conditions. The final diagnosis based on clinical follow-up was determined and classified as normal synovium, and different groups according to etiology. Total of 142 patients were analyzed. According to the score, case was classified to normal, low- or high-grade synovitis. ResultsThe synovitis scores in clinically normal synovium were low with 48 % of cases with scores of low-grade synovitis. In structural joint disorders scores varied from normal to low grade synovitis with occasional cases of high grade synovitis. In transient/reactive arthritis scores showed increase, majority clustering to low grade synovitis. In JIA and in bacterial synovitis the scores were higher than in the other groups high grade synovitis being the dominant grade. Extended oligoarthritis showed higher score than persistent oligoarthritis. ROC analysis indicated that JIA could be differentiated from other conditions. ConclusionsThe Krenn’s synovitis score is useful in the etiological classification of pediatric synovial samples, high Krenn’s score suggesting JIA. Observed differences between the subcategories of oligoarthritis may be useful in subclassifying these types of JIA.

Whipple disease diagnosed through minimally invasive ultrasound-guided synovial biopsy.

Whipple disease diagnosed through minimally invasive ultrasound-guided synovial biopsy.

Inclusion of fibrinoid necrosis increases the accuracy of synovial tissue assessment in predicting response to methotrexate: analysis of the UCLouvain Brussels ERA Cohort

ObjectiveRheumatoid Arthritis (RA) often exhibits suboptimal treatment response despite early diagnosis and treatment. This study aimed to analyze Early Rheumatoid Arthritis (ERA) synovial biopsies through histology and immunohistochemistry (IHC) to identify predictive factors for treatment response to Methotrexate (MTX).Methods140 ERA patients from the UCLouvain Arthritis Cohort underwent synovial biopsy and were monitored after initiating Disease-Modifying Antirheumatic Drug (DMARD) therapy. Histological features [Synovial Hyperplasia, Fibrinoid Necrosis (FN), Hypervascularization and Inflammatory Infiltrate] and IHC (CD3, CD20, CD138, CD68) were each semi-quantitatively assessed on a 0–3 scale with 7 levels.ResultsA strong association was observed between synovial CD68 and Fibrinoid Necrosis scores [r = 0.44 (0.27 − 0.56); p < 0.0001]. CD68 correlated with C-Reactive Protein (CRP), DAS28, SDAI and CDAI. Fibrinoid Necrosis score correlated with CRP and DAS28. Patients were then categorized as CD68NecrosisHIGH (CD68 + Necrosis ≥ 3) and CD68NecrosisLOW (CD68 + Necrosis < 3). CD68NecrosisHIGH exhibited higher pre-treatment disease activity [5.48 (1.6) versus 4.8 (1.7); p = 0.03] and a greater fall in DAS28 [1.99 (2.06) versus 1.1 (2.27), p = 0.03], SDAI [21.45 (IQR 23.3) versus 11.65 (IQR 17.5); p = 0.003] and CDAI [16 [14.9] versus 10.5 (20.1), p = 0.04]. CD68NecrosisHIGH patients had a higher EULAR Moderate/Good Response rate. CD68Necrosis score was incorporated into a probability matrix model together with clinical features (SJC44 and DAS28) to predict achieving a Moderate/Good EULAR Response Criteria at 3 months with a good performance (AUC 0.724).ConclusionFN and CD68 + in ERA synovial biopsies identify patients with higher disease activity and predict a better treatment response at three months. A model including synovial CD68 and fibrinoid necrosis with baseline clinical features predicts EULAR response at 3 months.

Two Broad Categories Overlapping With Rheumatoid Arthritis Observed in Synovial Biopsies from Patients With Juvenile Idiopathic Arthritis.

The objective is to characterize transcriptomic profiles and immune cell composition and distribution in juvenile idiopathic arthritis (JIA) synovial biopsies, assess for associations of these features with clinical parameters, and compare JIA and rheumatoid arthritis (RA) synovial features. RNA sequencing (RNASeq) was performed on 24 samples, with pathway analysis and inference of relative abundance of immune cell subsets based on gene expression data. Two multiplex fluorescence immunohistochemistry (IHC) panels were performed on 28 samples (including 13 on which RNASeq was performed), staining for CD206- classical and CD206+ nonclassical macrophages, and CD8+ and CD4+ T and B lymphocytes. Data were compared to a published series of early RA synovial biopsies. Pathway analysis of the most variably expressed genes (n = 339) identified a B and plasma cell signature as the main driver of heterogeneity in JIA synovia, with strong overlap between JIA and RA synovitis. Multiplex IHC confirmed heterogeneity of immune cell infiltration. M1-like macrophage-rich synovial lining was associated with greater lining hypertrophy and higher (CD45+) pan-immune cell and CD8+ T cell infiltration. Our study indicates significant similarities between JIA and RA synovitis. Similar to RA, JIA synovia may be broadly categorized into two groups: (1) those with an inflammatory/adaptive immune transcriptomic signature, M1-like macrophage and CD8+ T cell infiltration, and thicker, M1-like macrophage-rich synovial lining, and (2) those with an M2-like macrophage transcriptomic signature, greater M2/M1-like macrophage ratios, and thinner, M2-like macrophage-rich synovial lining. Synovial features were not significantly associated with clinical parameters, likely because of group size and heterogeneity.

Immunophenotypic Landscape of synovial tissue in rheumatoid arthritis: Insights from ACPA status

ObjectiveTo examine the clinical features and synovial pathologies in rheumatoid arthritis (RA) patients across varying titers of circulating anti-citrullinated protein antibodies (ACPA). MethodologyWe devised a negative pressure suction and rebound synovial biopsy tool to enhance the yield of synovial biopsies, noted for its ease and safety of use. This research involved a retrospective examination of 60 active RA patients who underwent synovial biopsies with this tool from June to November 2023 at our institution. A range of disease activity markers were collected, including DAS28-CRP, ESR, CRP, count of swollen and tender joints, VAS pain scale, and so forth. Synovial tissue underwent HE staining and immunohistochemistry, including synovitis grading (GSS) and counting of B cells (CD20), T cells (CD3), macrophages (CD68), and plasma cells (CD138). Participantswere categorized into three groups as per ACPA titers: ACPA-negative (0–5U/mL), low-titer (5–20U/mL), and high-titer (above 20U/mL). The study compared the clinical features and synovial pathologies across these groups. ResultsOf the 60 RA patients, they were segregated into three groups based on ACPA titers: 20 in ACPA-negative, 9 in the low-titer group, and 31 in the high-titer group. No significant differences were observed in GSS scores, synovial cell proliferation and loss, matrix activation, inflammatory infiltration, and neovascularization among these groups (P > 0.05). The high-titer ACPA group demonstrated significantly increased counts of CD3+ T cells, CD20+ B cells, and CD68+ macrophages in synovial tissues compared to the ACPA-negative and low-titer groups (p < 0.05), along with a higher incidence of ectopic lymphoid neogenesis (p < 0.05). Ordinal logistic regression revealed that rheumatoid factor (RF), and counts of synovial T cells, B cells, macrophages, and ectopic lymphoid neogenesis correlated with ACPA titers (P < 0.05), particularly lymphoid neogenesis (OR = 3.63, P = 0.023). ConclusionRA patients with high-titer ACPA demonstrate elevated levels of inflammatory cell infiltration in synovial tissues, with ectopic lymphoid neogenesis showing a strong correlation with high ACPA positivity.

Association between synovial tissue damage and pain in late-stage knee osteoarthritis: A cross-sectional study

ObjectiveTo identify the presence and distribution of histopathological features of synovial inflammation and tissue damage, and to test their associations with US imaging measures of synovitis and patient-reported measures of pain in knee osteoarthritis (OA). DesignIn the cross-sectional study of 122 patients undergoing surgery for painful late-stage (Kellgren-Lawrence Grade 3 or 4) knee OA, we compared ultrasound (US) measures of synovitis (n=118) and pain (Knee Injury and Osteoarthritis Outcome Score) to histopathological measures of inflammation vs. synovial tissue damage in synovial tissue biopsies. Associations of histopathological features with US measures of inflammation or pain were assessed using linear or logistic regression, while controlling for covariates. ResultsHistopathological features of inflammation were associated with higher odds of moderate/severe US synovitis (OR=1.34 [95%CI 1.04, 1.74), whereas features of synovial tissue damage were associated with lower odds of moderate/severe US synovitis (OR = 0.77 [95%CI 0.57, 1.03]). Worse histopathological scores for synovial tissue damage were associated with more pain (-1.47 [95%CI -2.88, -0.05]), even while adjusting for synovial inflammation (-1.61 [95%CI -3.12, -0.10]). ConclusionsSynovial tissue damage is associated with pain in late-stage knee OA, independent from inflammation and radiographic damage. These novel findings suggest that preventing synovial tissue damage may be an important goal of disease-modifying OA therapy.

The predictive value and reliability of ultrasound-guided synovial aspiration and biopsies for diagnosing periprosthetic shoulder infections.

Preoperative diagnosis of periprosthetic shoulder infections (PSI) is difficult. Infections are mostly caused by low virulence bacteria and patients do not show typical signs of infection. The aim of this study was to determine the diagnostic value and reliability of ultrasound-guided biopsies for cultures alone and in combination with multiplex polymerase chain reaction (mPCR), serum markers, and/or synovial markers for the preoperative diagnosis of PSI in patients undergoing revision shoulder surgery. A prospective explorative diagnostic cohort study was performed including 55 patients undergoing revision shoulder replacement surgery. A shoulder puncture was performed preoperatively before incision to collect synovial fluid for mPCR analysis and for measurement of interleukin-6, calprotectin, white blood cell count (WBC), and polymorphonuclear cells. Also prior to revision surgery, six ultrasound-guided synovial tissue biopsies were collected for culture and two for mPCR analysis. A blood sample was obtained to determine serum C-reactive protein, WBC, and erythrocyte sedimentation rate. Six routine care tissue biopsies were taken during revision surgery and served as reference standard. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV; the primary outcome measure), and accuracy were calculated for ultrasound-guided biopsies, blood and synovial markers, mPCR, and combinations thereof. Routine tissue cultures were positive for infection in 24 patients. Cultures from ultrasound-guided biopsies diagnosed infection in 7 of these patients, yielding a sensitivity, specificity, PPV, NPV, and accuracy of 29.2%, 93.5%, 77.8%, 63.0%, and 65.6%, respectively. The best diagnostic value was found for the combination of ultrasound-guided biopsies for culture, synovial WBC, and calprotectin with a sensitivity of 69.2%, specificity of 80.0%, PPV of 69.2%, and NPV of 80.0%. Ultrasound-guided biopsies for cultures alone and in combination with mPCR, and/or blood and/or synovial markers are not reliable enough to use in clinical practice for the preoperative diagnosis of PSI. Diagnostic study level II.

Phosphoproteomic profiling of early rheumatoid arthritis synovium reveals active signalling pathways and differentiates inflammatory pathotypes

BackgroundKinases are intracellular signalling mediators and key to sustaining the inflammatory process in rheumatoid arthritis (RA). Oral inhibitors of Janus Kinase family (JAKs) are widely used in RA, while inhibitors of other kinase families e.g. phosphoinositide 3-kinase (PI3K) are under development. Most current biomarker platforms quantify mRNA/protein levels, but give no direct information on whether proteins are active/inactive. Phosphoproteome analysis has the potential to measure specific enzyme activation status at tissue level.MethodsWe validated the feasibility of phosphoproteome and total proteome analysis on 8 pre-treatment synovial biopsies from treatment-naive RA patients using label-free mass spectrometry, to identify active cell signalling pathways in synovial tissue which might explain failure to respond to RA therapeutics.ResultsDifferential expression analysis and functional enrichment revealed clear separation of phosphoproteome and proteome profiles between lymphoid and myeloid RA pathotypes. Abundance of specific phosphosites was associated with the degree of inflammatory state. The lymphoid pathotype was enriched with lymphoproliferative signalling phosphosites, including Mammalian Target Of Rapamycin (MTOR) signalling, whereas the myeloid pathotype was associated with Mitogen-Activated Protein Kinase (MAPK) and CDK mediated signalling. This analysis also highlighted novel kinases not previously linked to RA, such as Protein Kinase, DNA-Activated, Catalytic Subunit (PRKDC) in the myeloid pathotype. Several phosphosites correlated with clinical features, such as Disease-Activity-Score (DAS)-28, suggesting that phosphosite analysis has potential for identifying novel biomarkers at tissue-level of disease severity and prognosis.ConclusionsSpecific phosphoproteome/proteome signatures delineate RA pathotypes and may have clinical utility for stratifying patients for personalised medicine in RA.

Surgical Procedures for the Non-Surgeon: A Rheumatology Perspective

Each specialty of medicine (and surgery) employs certain technical procedures appropriate to their specialty. Occasionally, those procedures require performance in an operating room environment. With the O.R. considered the province of the surgeon, such trespass by non-surgeons is not always well accepted. Rheumatologists seeking to develop arthroscopy as a tool for arthritis patients encountered such resistance but were able to persist and now perform any arthroscopy exclusively in a clinic or procedure room setting. Other procedures now performed by rheumatologists - arthrocentesis, joint washout, synovial biopsy, and labial salivary gland biopsy (lip biopsy) -all had their beginnings in the operating room, but no longer require such an environment. Non-surgeons - including rheumatologists - seeking to develop new invasive procedures may continue to utilize the O.R. in early stages when caution and safety concerns demand high level support, and sterile technique. The history of development of these procedures shows a common path to bedside performance. Any O.R. turf touched by a non-surgeon is only temporary.

Synovial fibroblast gene expression is associated with sensory nerve growth and pain in rheumatoid arthritis.

It has been presumed that rheumatoid arthritis (RA) joint pain is related to inflammation in the synovium; however, recent studies reveal that pain scores in patients do not correlate with synovial inflammation. We developed a machine-learning approach (graph-based gene expression module identification or GbGMI) to identify an 815-gene expression module associated with pain in synovial biopsy samples from patients with established RA who had limited synovial inflammation at arthroplasty. We then validated this finding in an independent cohort of synovial biopsy samples from patients who had early untreated RA with little inflammation. Single-cell RNA sequencing analyses indicated that most of these 815 genes were most robustly expressed by lining layer synovial fibroblasts. Receptor-ligand interaction analysis predicted cross-talk between human lining layer fibroblasts and human dorsal root ganglion neurons expressing calcitonin gene-related peptide (CGRP+). Both RA synovial fibroblast culture supernatant and netrin-4, which is abundantly expressed by lining fibroblasts and was within the GbGMI-identified pain-associated gene module, increased the branching of pain-sensitive murine CGRP+ dorsal root ganglion neurons in vitro. Imaging of solvent-cleared synovial tissue with little inflammation from humans with RA revealed CGRP+ pain-sensing neurons encasing blood vessels growing into synovial hypertrophic papilla. Together, these findings support a model whereby synovial lining fibroblasts express genes associated with pain that enhance the growth of pain-sensing neurons into regions of synovial hypertrophy in RA.

Rheumatoid arthritis: pathogenesis and therapeutic advances.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the unresolved synovial inflammation for tissues-destructive consequence, which remains one of significant causes of disability and labor loss, affecting about 0.2-1% global population. Although treatments with disease-modifying antirheumatic drugs (DMARDs) are effective to control inflammation and decrease bone destruction, the overall remission rates of RA still stay at a low level. Therefore, uncovering the pathogenesis of RA and expediting clinical transformation are imminently in need. Here, we summarize the immunological basis, inflammatory pathways, genetic and epigenetic alterations, and metabolic disorders in RA, with highlights on the abnormality of immune cells atlas, epigenetics, and immunometabolism. Besides an overview of first-line medications including conventional DMARDs, biologics, and small molecule agents, we discuss in depth promising targeted therapies under clinical or preclinical trials, especially epigenetic and metabolic regulators. Additionally, prospects on precision medicine based on synovial biopsy or RNA-sequencing and cell therapies of mesenchymal stem cells or chimeric antigen receptor T-cell are also looked forward. The advancements of pathogenesis and innovations of therapies in RA accelerates the progress of RA treatments.

Precision Medicine in Rheumatology: The Promise of Ultrasound-Guided Synovial Biopsy, Barriers to Its Implementation in the United States, and Proposed Solutions.

In the clinical evaluation of inflammatory arthritis and the research into its pathogenesis, there is a growing role for the direct analysis of synovial tissue. Over the years, various biopsy techniques have been used to obtain human synovial tissue samples, and there have been progressive improvements in the safety, tolerability, and utility of the procedure. The latest advancement in synovial tissue biopsy techniques is the use of ultrasound imaging to guide the biopsy device, along with evolution in the characteristics of the device itself. While ultrasound guided synovial biopsy (UGSB) has taken a strong foothold in Europe, the procedure is still relatively new to the United States of America (USA). In this paper, we describe the expansion of UGSB in the USA, elucidate the challenges faced by rheumatologists developing UGSB programs in the USA, and describe several strategies for overcoming these challenges.

Intensive training programme for ultrasound-guided minimally invasive synovial tissue biopsy on knees and wrists in different phases of inflammation

ObjectivesTo develop an intensive training programme for ultrasound (US)-guided synovial tissue (ST) biopsy on knees and wrists in inflammatory arthritis and to assess the learning curve, patient tolerability, sample quality...

High-grade synovitis associates with clinical markers and response to therapy in chronic inflammatory arthritis: post hoc analysis of a synovial biomarkers prospective cohort study.

Inflammatory arthritis (IAs), such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA), are characterized by the presence of chronic synovitis. The Krenn's synovitis score (KSS), a simple tool detectable by haematoxylin/eosin staining of synovial biopsy samples, allows the discrimination between high-grade and low-grade synovitis. The aim of this study was to identify the clinical associations of KSS and to evaluate the relationship between high-grade synovitis and treatment response in IA patients. Clinical, laboratory and ultrasound data were retrieved from RA and PsA patients recruited in the prospective MATRIX cohort study. Inclusion criteria were age≥18 years, RA or PsA diagnosis, and presence of active disease with eligibility to start/modify therapy. Patients underwent ultrasound-guided synovial biopsy of one of the most involved joints before starting/modifying treatment according to treat-to-target strategy. The samples were analysed by an expert pathologist for KSS calculation. Univariable and multivariable logistic regression analyses were performed to evaluate the relationship between KSS and baseline variables. The association between KSS and treatment response at 24 weeks of follow-up was investigated in univariable logistic regression analysis. 53 patients, 34 RA and 19 PsA, completed 24 weeks of follow-up after synovial biopsy. Patients were either treatment naïve (N=6, 11%), csDMARDs-experienced (N=46, 87%) or b/tsDMARDs-experienced (N=20, 38%). Median KSS was 6.00 (Q1-Q3 4.00-7.00) in RA and 4.00 (3.00-6.00) in PsA (p=0.040), and inflammatory infiltrates score was significantly higher in RA than in PsA patients (median 3.00 vs 2.00, p=0.021). In multivariable analysis, synovial effusion in the biopsied joint (OR 9.26, 95%CI 2.12-53.91) and erythrocyte sedimentation rate (ESR) (OR 1.04, 95%CI 1.01-1.08) associated with high KSS. High-grade synovitis significantly associated with a higher probability of achieving DAS28 remission, ACR20/50 response, and Boolean2.0 remission, independently from diagnosis. Several markers of pro-inflammatory pathways associated with the presence of high-grade synovitis, and patients with higher KSS shared a higher probability of treatment targets achievement in the follow up. The integration of a simple and feasible tool like KSS in the clinical and prognostic stratification of patients with IA might help in intercepting patients with a disease more prone to respond to available treatment paradigms.

Synovial tissue features associated with poor prognosis in inflammatory arthritis

BackgroundInflammatory arthritis encompasses a group of immune-mediated diseases characterized by chronic joint inflammation. Despite having pathogenic mechanisms in common, the prognosis of rheumatoid arthritis (RA), psoriatic arthritis (PsA), and undifferentiated arthritis (UA) could be different regarding progression to chronic, to erosive, or to self-limited disease. Our aim was to evaluate the potential association of synovial tissue (ST) inflammatory cell infiltrate, the presence of ectopic lymphoid neogenesis (LN +) structures, and poor prognosis factors (PPF) in patients with RA, PsA, and UA.MethodsWe conducted a retrospective study including patients with active arthritis (RA, PsA, UA) who had ST obtained by rheumatological arthroscopy or ultrasound-guided biopsy. Clinical, demographic, and immunohistochemical data of the synovium was evaluated. Patients with biological therapy at the time of synovial biopsy were excluded. PPF in patients with RA and UA were defined by the presence of anti-cyclic citrullinated peptide antibodies and/or rheumatoid factor, development of bone erosions, or requirement of biological therapy during the follow-up. PPF in patients with PsA were defined as the presence of high levels of acute-phase reactants (ESR/CRP), dactylitis or nail involvement at the time of biopsy, development of bone erosion, or requirement of biological therapy during the follow-up.ResultsA total of 88 patients were included: 26 RA, 33 PsA, and 29 UA. All patients were followed up for 5 years after the biopsy. Fourteen (53.84%) RA patients had PPF, and 17 (65.38%) had LN + . LN + was associated with PPF (p 0.038) and biologic therapy initiation (p 0.018). A total of 14 (43.75%) PsA patients had PPF. CD15 infiltrate (410.68 [SD 477.63] cells/mm2) was associated with PPF (p 0.008) in PsA patients. Sixteen (55.17%) patients with UA had PPF, and 13 (44.82%) had LN + . In this group, synovial CD68 + macrophages cells density was negatively correlated with DAS28-CRP (r = − 0.346, p 0.042).ConclusionsThe presence of LN + and higher CD15 + polymorphonuclear cells infiltrate was associated with PPF in RA and PsA, respectively. No associations were found for UA. These findings suggest a great heterogeneity of the ST features and its pathogenic implications in the subtypes of inflammatory arthritis.