Béatrice Andre

(18)F-FDG PET imaging of rheumatoid knee synovitis correlates with dynamic magnetic resonance and sonographic assessments as well as with the serum level of metalloproteinase-3.

PurposeThe aim of this study was to assess rheumatoid arthritis (RA) synovitis with positron emission tomography (PET) and 18F-fluorodeoxyglucose (18F-FDG) in comparison with dynamic magnetic resonance imaging (MRI) and ultrasonography (US).MethodsSixteen knees in 16 patients with active RA were assessed with PET, MRI and US at baseline and 4 weeks after initiation of anti-TNF-α treatment. All studies were performed within 4 days. Visual and semi-quantitative (standardised uptake value, SUV) analyses of the synovial uptake of FDG were performed. The dynamic enhancement rate and the static enhancement were measured after i.v. gadolinium injection and the synovial thickness was measured in the medial, lateral patellar and suprapatellar recesses by US. Serum levels of C-reactive protein (CRP) and metalloproteinase-3 (MMP-3) were also measured.ResultsPET was positive in 69% of knees while MRI and US were positive in 69% and 75%. Positivity on one imaging technique was strongly associated with positivity on the other two. PET-positive knees exhibited significantly higher SUVs, higher MRI parameters and greater synovial thickness compared with PET-negative knees, whereas serum CRP and MMP-3 levels were not significantly different. SUVs were significantly correlated with all MRI parameters, with synovial thickness and with serum CRP and MMP-3 levels at baseline. Changes in SUVs after 4 weeks were also correlated with changes in MRI parameters and in serum CRP and MMP-3 levels, but not with changes in synovial thickness.Conclusion18F-FDG PET is a unique imaging technique for assessing the metabolic activity of synovitis. The PET findings are correlated with MRI and US assessments of the pannus in RA, as well as with the classical serum parameter of inflammation, CRP, and the synovium-derived parameter, serum MMP-3. Further studies are warranted to establish the place of metabolic imaging of synovitis in RA.

Modulation of proteolytic activity during neuritogenesis in the PC12 nerve cell: differential control of plasminogen activator and plasminogen activator inhibitor activities by nerve growth factor and dibutyryl-cyclic AMP.

Extracellular proteolysis is considered to be required during neuritic outgrowth to control the adhesiveness between the growing neurite membrane and extracellular matrix proteins. In this work, PC12 nerve cells were used to study the modulation of proteolytic activity during neuronal differentiation. PC12 cells were found to contain and release a 70–75‐kDa tissue‐type plasminogen activator (tPA) and a much less abundant 48‐kDa urokinase‐type plasminogen activator. A plasminogen activator inhibitor (PAI) activity with molecular sizes of 54 and 58 kDa was also detected in PC12 cell conditioned medium and formed high‐molecular‐mass complexes with released tPA. Release of PAI activity was dependent on treatment with nerve growth factor (NGF), whereas tPA synthesis and release were under control of a cyclic AMP‐ dependent mechanism and increased on treatment with dibutyryl‐cyclic AMP [(But)2cAMP] or cholera toxin. Simultaneous treatment with NGF and (But)2cAMP resulted in increases of both tPA and PAI release and enhancement of tPA‐PAI complex formation. The resulting plasminogen activator activity in conditioned medium was high in (But)2cAMP‐treated cultures with short neuritic outgrowth but remained low in NGF‐ or NGF plus (But)2 cAMP‐treated cultures, where neurite extension was, respectively, large and very large. These results suggest that excess proteolytic activity may be detrimental to neuritic outgrowth and that not only PAI release but also tPA‐PAI complex formation is associated with production of large and stable neuritic outgrowth. This can be understood as an involvement of PAI in the protection against neurite‐destabilizing proteolytic activity.

Increased synovial fluid levels of soluble CD23 are associated with an erosive status in rheumatoid arthritis (RA)

Synovial fluid (SF) levels of soluble CD23 (sCD23) were determined in 96 patients presenting with an inflammatory knee effusion (73 with RA and 23 with reactive arthritis (ReA) serving as a control inflammatory non‐erosive group) and were correlated with the degree of joint destruction, with local immune parameters (IL‐1β, IL‐3, IL‐4, IL‐6, IL‐8, IL‐10, IL‐12 and sCD25) and with serum markers of inflammation, C‐reactive protein and erythrocyte sedimentation rate. RA patients, classified as erosive or not according to Larsen’s grade, were separated as follows: (i) 13 patients with non‐erosive RA; (ii) 16 RA patients with erosions in hands but not in knees, matched for disease duration with the first group; (iii) 44 RA patients with hand and knee erosions, matched with the second group for rheumatoid factor positivity but of longer disease duration. SF sCD23 levels were significantly increased in both erosive RA groups compared with non‐erosive diseases, whether RA or ReA (P < 0·05), whose SF levels were not different. SF IL‐10 showed a similar profile to that of SF sCD23 and was the only other parameter characteristic of erosive RA, but no direct correlation was found between the two. SF sCD23 was significantly correlated with IL‐12 (r = 0·65, P = 0·0001) and sCD25 (r = 0·39, P = 0·0019) exclusively in the two erosive RA populations. In conclusion, these data showing that increased levels of sCD23 are not only found in the SF of erosive joints but also in knee SF of patients with erosive RA but without knee x‐ray‐diagnosed erosions suggest that this parameter might be of predictive value for joint destruction. Longitudinal studies are however needed to confirm its potential clinical interest.

Cardiovascular outcome in systemic sclerosis.

OBJECTIVES Cardiovascular involvement is recognized as a poor prognostic factor in systemic sclerosis (SSc). The aim of this study was to evaluate the usefulness of nailfold video-capillaroscopy (NVC), brain natriuretic peptide (BNP) blood level and exercise echocardiography to predict the occurrence of cardiovascular events in SSc. METHODS We prospectively enrolled 65 patients with SSc (age 54±14 years, 30% female) followed in CHU Sart-Tilman, Liège, Belgium. All patients underwent graded semi-supine exercise echocardiography. Both baseline resting pulmonary hypertension (PH) and PH during follow-up (FUPH) were defined as systolic pulmonary arterial pressure (sPAP)>35 mmHg, and exercise-induced PH (EIPH) as sPAP>50 mmHg during exercise. RESULTS EIPH was present in 21 patients. During FU (27±18 months), 13 patients developed FUPH and 9 presented cardiovascular complications. Patients with cardiovascular events were significantly older (63±14 vs 52±13 years; P=0.03), presented more frequently NVC grade>2 (89 vs 43%; P=0.009), had higher resting and exercise sPAP (30±6 vs 24±6; P=0.007 and 57±13 vs 44±13 vs mmHg; P=0.01, respectively), and higher BNP blood level (112±106 vs 26±19 pg/ml; P=0.0001). After adjustment for age and gender, NVC grade>2 (ß=2.4±1.1; P=0.03), EIPH (ß=2.30±1.13; P=0.04), FUPH (ß=0.24±0.09; P=0.01 and ß=3.52±1.16; P=0.002, respectively;) and BNP (ß=0.08±0.04; P=0.02) were independent predictors of CV events. Beyond age, an incremental value of EIPH, BNP and NVC grade>2 was predictive of cardiovascular events (P<0.001). CONCLUSION Cardiovascular complications are not rare in SSc (18%). NVC, BNP blood level assessment and exercise echocardiography could be useful tools to identify patients at risk of SSc.