Jun Fukae

Change of synovial vascularity in a single finger joint assessed by power doppler sonography correlated with radiographic change in rheumatoid arthritis: comparative study of a novel quantitative score with a semiquantitative score.

To investigate the relationship between synovial vascularity assessed by quantitative power Doppler sonography (PDS) and progression of structural bone damage in a single finger joint in patients with rheumatoid arthritis (RA).

Defective Expression of Ras Guanyl Nucleotide-Releasing Protein 1 in a Subset of Patients with Systemic Lupus Erythematosus

Dysregulation of Ras guanyl nucleotide-releasing protein 1 (RasGRP1) in mice results in a systemic lupus erythematosus (SLE)-like disorder. We therefore looked for defective isoforms and/or diminished levels of human RasGRP1 in a cohort of SLE patients. PBMCs were collected from twenty healthy individuals and thirty-two patients with SLE. mRNA was isolated and five RasGRP1 cDNAs from each subject were sequenced. T cell lysates from healthy controls and SLE patients also were evaluated for their levels of RasGRP1 protein. The accumulated data led to the identification of 13 new splice variants of the human RasGRP1 gene. Not only did our SLE patients have increased levels and types of these defective transcripts relative to normal individuals, two SLE patients were identified whose PBMCs and T cells contained very little, if any, functional RasGRP1 mRNA and protein. The presence of aberrantly spliced RasGRP1 transcripts also was correlated with lower levels of RasGRP1 protein in the patients’ T cells. The lack of the normal isoform of RasGRP1 in some SLE patients and the increased prevalence of defective isoforms of RasGRP1 in others raise the possibility that dysregulation of this signaling protein contributes to the development of autoimmunity in a subset of SLE patients.

Radiographic prognosis of finger joint damage predicted by early alteration in synovial vascularity in patients with rheumatoid arthritis: Potential utility of power doppler sonography in clinical practice.

To investigate the relationship between synovial vascularity and progression of structural bone damage in each finger joint in patients with rheumatoid arthritis (RA) and to demonstrate synovial vascularity as a potential therapeutic marker.

Screening for rheumatoid arthritis with finger joint power Doppler ultrasonography: quantification of conventional power Doppler ultrasonographic scoring

Power Doppler ultrasonography (PD-US) has proved to be a useful technique to measure synovial vascularity due to its capability to provide data that can be used to evaluate the level of joint inflammation and assess rheumatoid arthritis (RA). We have developed a novel PD-US finger joint scoring method that introduces quantitative measurements into the conventional PD-US assessment method. A comparison of the two methods revealed that our novel PD-US method strongly correlates with the conventional method in terms of RA assessment. We performed finger joint PD-US on 69 patients with RA and 70 patients who had multiple joint pain but showed no evidence of inflammatory diseases (non-inflammatory disease, NI) and measured the synovial vascularity of the metacarpophalangeal joints 1–5 and proximal interphalangeal (PIP) joints 1–5 for each patient. We analyzed the data with receiver operating characteristic analysis and, based on the results for the total vascularity of 20 finger joints, defined a cut-off value of 36% as discriminating between RA and NI. This cut-off value was found to be a valuable tool in screening for RA. We conclude that our finger joint PD-US scoring system is both useful and applicable for diagnosing RA.

Sonographic synovial vascularity of synovitis in rheumatoid arthritis

RA is a condition of multiple synovitis. Abnormal synovial vascularity (SV) is evident with the onset of joint inflammation. The idea of estimating the level of joint inflammation by sonographic SV was conceived with the advancement of US. The ideal treatment strategy, called treat to target (T2T), requires early diagnosis and assessment of RA. Detection of positive SV can be useful for proving the presence of synovitis and finally diagnosing RA. In the assessment of RA, US-based global scores aimed at assessing overall disease activity have the potential to be useful for the achievement of T2T because US can directly detect changes in synovitis. Remaining SV in local joints increases the risk of structural deterioration. RA requires both improvement of overall disease activity and the disappearance of local SV for remission. The evaluation of SV provides various information and contributes to the clinical treatment of RA.

Positive synovial vascularity in patients with low disease activity indicates smouldering inflammation leading to joint damage in rheumatoid arthritis: time-integrated joint inflammation estimated by synovial vascularity in each finger joint

OBJECTIVE To investigate the relationship between synovial vascularity and joint damage progression in each finger joint of patients with RA under low disease activity during treatment with biologic agents. METHODS We studied 310 MCP and 310 PIP joints of 31 patients with active RA who were administered adalimumab (ADA) or tocilizumab (TCZ). Patients were examined with clinical and laboratory assessments. Power Doppler sonography was performed at baseline and at weeks 8, 20 and 40. Synovial vascularity was evaluated according to quantitative measurement. Hand and foot radiography was performed at baseline and at week 50. RESULTS Composite scores of the DAS with 28 joints and the Simplified Disease Activity Index (SDAI) were significantly decreased from baseline to week 8, being sustained at a low level by biologic agents during the observational period. MCP and PIP joints with positive synovial vascularity after week 8 showed more subsequent joint damage progression than joints without synovial vascularity throughout the follow-up. The changes in radiographic progression in these joints were independent of the sum of synovial vascularity from baseline to week 40 or the occasional occurrence of positive synovial vascularity. CONCLUSION Smouldering inflammation reflected by positive synovial vascularity under low disease activity was linked to joint damage. The damage progressed irrespective of the severity of positive synovial vascularity. Even with a favourable overall therapeutic response, monitoring of synovial vascularity has the potential to provide useful joint information to tailor treatment strategies. Trial registration. University Hospital Medical Information Network Clinical Trials Registry; http://www.umin.ac.jp/ctr/; UMIN000004476.

Structural deterioration of finger joints with ultrasonographic synovitis in rheumatoid arthritis patients with clinical low disease activity

OBJECTIVE In this study we investigated the relationship between synovial vascularity (SV) and structural alteration of finger joints in patients with RA and long-term sustained clinical low disease activity (CLDA). METHODS RA patients with CLDA of >2 years (minimum 1 year of CLDA for study entry plus 1 year of observation) were analysed. Quantitative SV values were sequentially measured in each finger joint using power Doppler ultrasonography (0, 8, 20 and 52 weeks). Radiological progression of local finger joints was evaluated according to the Genant-modified Sharp score (0-52 weeks). RESULTS Of the 25 patients enrolled, 15 patients were finally analysed after excluding 10 patients who failed to maintain CLDA during the observational period. Changes in radiological progression of MCP and PIP joints with positive SV were significantly greater than those in joints with negative SV. Joint space narrowing (JSN) was strongly related to structural alteration of finger joints. In joints with positive SV, changes in structural alteration did not relate to total SV values, which reflect total exposure to inflammation in an observational period. CONCLUSION Even in patients with a long period of CLDA, finger joints with positive SV showed structural alteration, especially in the progression of JSN. TRIAL REGISTRATION University Hospital Medical Information Network Clinical Trials Registry, http://www.umin.ac.jp/ctr/, UMIN000007305.

Ultrasound Assessment of Synovial Pathologic Features in Rheumatoid Arthritis Using Comprehensive Multiplane Images of the Second Metacarpophalangeal Joint: Identification of the Components That Are Reliable and Influential on the Global Assessment of the Whole Joint

The aim of this pilot study was to provide groundwork that could be utilized to optimize the global ultrasound (US) assessment of the whole joint for synovial pathologic features in patients with rheumatoid arthritis (RA).

Analysis of the factors which influence the measurement of synovial power Doppler signals with semi-quantitative and quantitative measures - a pilot multicenter exercise in Japan.

Abstract Objectives. This pilot multicenter exercise aimed to evaluate the inter-observer reproducibility of synovial power Doppler (PD) signals in rheumatoid arthritis (RA) patients and to determine the factors influencing the measurements. Methods. Two representative RA patients were assessed by four independent experienced sonographers. The influence of machine difference, deterioration of the transducer and pulse repetition frequency (PRF) on the assessment of synovial PD signals was investigated. Results. Intra-class correlation coefficient (ICC) for the scanner–reader reproducibility of semi-quantitative PD score was high (0.867). ICC for the inter-scanner reproducibility of synovial PD pixel count was higher than that of semi-quantitative PD score. The assessment of PD signals significantly differed between two machines with quantitative measurements but did not with semi-quantitative score. The assessment of PD signals with a deteriorated transducer was much less sensitive than that with an intact one. The semi-quantitative scores for PD signals were comparable between three different PRFs (500/800/1,300 Hz), whereas the pixel count was significantly lower with the highest one in the knee joint. Conclusions. Measurement of PD signal can be substantially affected by deteriorated quality of the transducer, whereas the differences are relatively modest between machines with similar specifications and also between PRF settings within a low range.

Computer-Based Radiographic Quantification of Joint Space Narrowing Progression Using Sequential Hand Radiographs: Validation Study in Rheumatoid Arthritis Patients from Multiple Institutions

We have developed a refined computer-based method to detect joint space narrowing (JSN) progression with the joint space narrowing progression index (JSNPI) by superimposing sequential hand radiographs. The purpose of this study is to assess the validity of a computer-based method using images obtained from multiple institutions in rheumatoid arthritis (RA) patients. Sequential hand radiographs of 42 patients (37 females and 5 males) with RA from two institutions were analyzed by a computer-based method and visual scoring systems as a standard of reference. The JSNPI above the smallest detectable difference (SDD) defined JSN progression on the joint level. The sensitivity and specificity of the computer-based method for JSN progression was calculated using the SDD and a receiver operating characteristic (ROC) curve. Out of 314 metacarpophalangeal joints, 34 joints progressed based on the SDD, while 11 joints widened. Twenty-one joints progressed in the computer-based method, 11 joints in the scoring systems, and 13 joints in both methods. Based on the SDD, we found lower sensitivity and higher specificity with 54.2 and 92.8%, respectively. At the most discriminant cutoff point according to the ROC curve, the sensitivity and specificity was 70.8 and 81.7%, respectively. The proposed computer-based method provides quantitative measurement of JSN progression using sequential hand radiographs and may be a useful tool in follow-up assessment of joint damage in RA patients.