Sonographic joint assessment in rheumatoid arthritis: associations with clinical joint assessment during a state of remission.

OBJECTIVE: Sonography, as compared with clinical assessment, is a sensitive tool for evaluating synovitis in rheumatoid arthritis (RA). However, differences between these assessment tools may depend on how joint activity (i.e., an active joint) is defined. The present study was undertaken to compare clinically active joints with sonographically active joints in patients with RA, applying different sonographic definitions of an active joint. METHODS: Sonographic assessment of the finger and wrist joints (total of 11 joints) of each hand was performed in RA patients whose disease was in remission (Clinical Disease Activity Index ≤2.8; n = 60). Gray-scale (GS) and power Doppler (PD) ultrasound signals for synovitis were evaluated on a 4-point scale (grade 0 = none, grade 3 = severe). The sensitivity and specificity of swollen joint counts were investigated using, as reference, increasingly stringent sonographic definitions of an active joint. Sonographic findings were also assessed for correlations with other clinical variables, including the Health Assessment Questionnaire (HAQ) disability index (DI). Followup analyses were performed after 6-12 months. RESULTS: GS ultrasound signals yielded positive findings for synovitis in 67.2% of the 1,320 joints assessed, and PD ultrasound signals indicated signs of synovitis in 20.4% of the joints assessed. Clinical identification of joint swelling was 100% specific for sonographic joint activity, independent of the stringency of the sonographic definition used; maximum sensitivity of the swollen joint counts was 25% for the most stringent definition (i.e., GS grade 3 and PD grade 3). Furthermore, patients with a higher-grade PD signal (grade 3) showed a higher HAQ DI score compared to patients with lower-grade PD signals (mean ± SD HAQ DI 0.45 ± 0.62 versus 0.20 ± 0.35). A higher grade of PD signal at baseline was found in joints that were assessed as clinically swollen at the consecutive followup visit. CONCLUSION: Low-grade PD and GS ultrasound signals may not necessarily reflect the presence of active synovitis in RA joints. High-grade PD signals correlate well with the presence of clinical joint swelling and clinical disease activity, and a higher grade of PD signal is associated with higher degrees of functional impairment.

Immediate access rheumatology clinic: efficiency and outcomes.

OBJECTIVE AND METHODS: In order to facilitate access and shorten waiting times to rheumatologist assessment, an immediate access clinic (IAC) was established. Patients were assessed at presentation in the clinic and after 6-12 months, either in the clinic or by telephone. Data regarding diagnostic accuracy, pain levels and care were analysed. RESULTS: From February to December 2009, 1036 patients were assessed. 223 (21.5%) patients had symptoms for 3 months or less. 660 were available for re-assessment after 6-12 months. Initial tentative diagnoses were confirmed in over 75% of patients suspected of having rheumatoid arthritis (RA), spondylarthropathy and osteoarthritis. Men suspected of having spondylarthropathy had a significantly longer symptom duration than women (median (IQR) 54.0 (18.0-120.0) vs 24.0 (6.0-66.0) months; p=0.0082). There was no significant gender difference regarding pain. At follow-up, the visual analogue scale for pain in RA patients admitted to further care in the clinic (n=61) had significantly decreased by a median (IQR) of 37.5 mm (10.5-50.5), whereas this improvement was only 6 mm (-26-33.5) in the 22 RA patients followed outside the clinic (p=0.0083). CONCLUSIONS: The IAC resulted in considerable waiting time reduction for rheumatology assessment. A substantial minority was seen before 3 months' symptom duration. 'Positive predictive correctness' of the assessing rheumatologists regarding the presence of inflammatory rheumatic conditions was over 75%. Patients with RA cared for in the clinic had substantially lower pain levels after 6-12 months' follow-up than patients treated elsewhere.

The zymogen granule protein 2 (GP2) binds to scavenger receptor expressed on endothelial cells I (SREC-I).

The pancreatic zymogen granule membrane protein (GP2) is expressed by pancreatic acinar cells and M cells of the ileum. GP2 is the closest related homologue of the urine resident Tamm-Horsfall protein (THP). Recently, it was shown that THP is a ligand of various scavenger receptors (SRs). Therefore, we were interested, if GP2 has similar properties. cDNA of different SRs was stably transfected into a murine thymoma cell line. GP2 was recombinantly expressed, purified and biotinylated. Binding or uptake of GP2 by transfected cells or monocyte-derived dendritic cells (moDCs) was analyzed by flow-cytometry. GP2 is a binding partner of the scavenger receptor expressed on endothelial cells I (SREC-I) but not of SR-AI and SR-BI. The dissociation constant (K(d)) of GP2 binding to SREC-I is 41.3nM. SREC transfected cells are able to internalize GP2. moDCs express SREC-I and also bind and internalize GP2. Inhibition of SREC-I on moDCs with anti-SREC-I antibodies does not result in a decreased GP2 binding. Interaction of GP2 with SREC-I and uptake might have profound effects in antigen clearance and mediation of the immune response. In addition to SREC-I other presently unknown receptors for GP2 on DCs might be involved in this process.

Quantification of α-galactosidase activity in intact leukocytes.

BACKGROUND: Mutations of the α-galactosidase (α-Gal) A gene in Fabry disease lead to a severe disturbance in glycosphingolipid catabolism. The atypical clinical picture of Fabry disease hampers diagnosis, resulting in a delayed start of therapy. Current tests utilize leukocyte lysates to evaluate the activity of α-Gal A. It has never been investigated whether cell homogenisation is necessary. METHODS: Isolated leukocyte subsets were incubated with the α-Gal substrate methylumbelliferyl-α-D galactopyranosid (MU-Gal) and substrate conversion was measured by fluorimetry. Specificity of the reaction was evaluated using the α-Gal inhibitor deoxygalactonojirimycin (DGJ). The novel procedure was compared to the standard method. A reference population and Fabry patients were tested. RESULTS: Substrate conversion in intact leukocytes was a function of substrate concentration, cell number and time and could be inhibited by DGJ. Monocytes showed the highest enzyme activity among leukocyte populations. The novel procedure highly correlated with the standard method. Both Fabry hemizygotes and heterozygotes showed reduced substrate conversion. CONCLUSION: We here present a novel sensitive, fast and simple procedure for the evaluation of α-Gal activity suitable to identify enzyme deficiencies in Fabry patients. Furthermore, we show for the first time that leukocyte subtypes have different α-Gal activities.