Anti-citrullinated protein antibodies in the diagnosis of rheumatoid arthritis (RA): diagnostic performance of automated anti-CCP-2 and anti-CCP-3 antibodies assays

This study compares the diagnostic performance of a second generation anti-cyclic citrullinated peptide antibody (CCP2) with a third generation anti-CCP antibodies assay (CCP3), as well as the combination of both tests. Serum samples of 127 patients were analyzed. IgG anti-CCP 2 and IgM rheumatoid factor were determined by EliA™ technique on a Phadia 250 instrument (Thermo Fisher Scientific), anti-CCP3 by the Quanta Flash™ anti-CCP3 IgG kit, BIO-FLASH Rapid Response Chemiluminscence Analyzer (INOVA Diagnostics). Diagnostic performance was compared using ROC-curves, sensitivity, specificity, likelihood ratios, and predictive values. Logistic regressions were used to investigate whether using both tests (anti-CCP2 and anti-CCP3) gives a better prediction of rheumatoid arthritis. At the manufacturer’s cut-offs sensitivity and specificity were 79.4 and 61.0% for CCP3 and 80.9 and 69.5% for CCP2. No significant differences could be observed regarding the areas under the curve (AUC) of both ROC-curves. The optimal cut-off point for CCP2 was 10.5 U/ml (sensitivity of 75.0% and specificity of 80.0%) and 5.6 U/ml for CCP3 (sensitivity of 86.9% and specificity of 61.0%). Binary logistic regressions indicated that the likelihood of having rheumatoid arthritis (RA) is significantly higher when testing positive on both CCP2 and CCP3 compared to CCP2 or CCP3 alone. In our cohort, comparable performance was found between the two CCP assays. Positivity for both CCP2 and CCP3 resulted in the most specific identification of RA patients. In patients with joint complaints suspected of having RA and with a weakly positive CCP 2 (≥7 and ≤16 U/ml) CCP3 testing could be of additive value for diagnosing RA

Long Term Cyclic Pamidronate Reduces Bone Growth by Inhibiting Osteoclast Mediated Cartilage-to-Bone Turnover in the Mouse

Bisphosphonates, used to treat diseases exhibiting increased osteoclast activity, reduce longitudinal bone growth through an as yet undefined mechanism. Pamidronate, an aminobisphosphonate, was given weekly to mice at 0, 1.25, or 2.50 mg/kg/wk beginning at 4 weeks of age. At 12 weeks of age, humeral length, growth plate area, regional chondrocyte cell numbers, chondrocyte apoptosis, TRAP stained osteoclast number, and osteoclast function assessed by cathepsin K immunohistochemistry were quantified. Humeral length was decreased in pamidronate treated mice compared to vehicle control mice, and correlated with greater growth plate areas reflecting greater proliferative and hypertrophic chondrocyte cell numbers with fewer hypertrophic cells undergoing apoptosis. Pamidronate treatment increased TRAP stained osteoclast numbers yet decreased cathepsin K indicating that pamidronate repressed osteoclast maturation and function. The data suggest that long term cyclic pamidronate treatment impairs bone growth by inhibition of osteoclast maturation thereby reducing cartilage-to-bone turnover within the growth plate

Flemish network on rare connective tissue diseases (CTD): patient pathways in systemic sclerosis. First steps taken.

peer reviewedDespite the low prevalence of each rare disease, the total burden is high. Patients with rare diseases encounter numerous barriers, including delayed diagnosis and limited access to high-quality treatments. In order to tackle these challenges, the European Commission launched the European Reference Networks (ERNs), cross-border networks of healthcare providers and patients representatives. In parallel, the aims and structure of these ERNs were translated at the federal and regional levels, resulting in the creation of the Flemish Network of Rare Diseases. In line with the mission of the ERNs and to ensure equal access to care, we describe as first patient pathways for systemic sclerosis (SSc), as a pilot model for other rare connective and musculoskeletal diseases. Consensus was reached on following key messages: 1. Patients with SSc should have multidisciplinary clinical and investigational evaluations in a tertiary reference expert centre at baseline, and subsequently every three to 5 years. Intermediately, a yearly clinical evaluation should be provided in the reference centre, whilst SSc technical evaluations are permissionably executed in a centre that follows SSc-specific clinical practice guidelines. In between, monitoring can take place in secondary care units, under the condition that qualitative examinations and care including interactive multidisciplinary consultations can be provided. 2. Patients with early diffuse cutaneous SSc, (progressive) interstitial lung disease and/or pulmonary arterial hypertension should undergo regular evaluations in specialised tertiary care reference institutions. 3. Monitoring of patients with progressive interstitial lung disease and/or pulmonary (arterial) hypertension will be done in agreement with experts of ERN LUNG

Bartonella endocarditis mimicking adult Still's disease

We describe the case of a 39-year-old Caucasian woman who was admitted to the University Hospital of Antwerp with a clinical picture suggestive of adult Still's disease. Even though a transoesophageal echocardiography showed endocarditis of the aortic valve, blood cultures remained negative. Additional serological testing revealed a positive result for Bartonella henselae. Histology of the supraclavicular lymph node showed a reactive lymph node with a positive polymerase chain reaction (PCR) for Bartonella henselae. Prednisolone treatment was started in a dosage of 10 mg per day and rifampicin 600 mg/d in combination with doxycyclin 200 mg/d was given for 6 months. During therapy the patient gradually improved and signs of endocarditis disappeared on echocardiography

Effect of bisphosphonates on viability, proliferation, and dexamethasone-induced apoptosis of articular chondrocytes

Objectives: To study the influence of BP on articular chondrocytes in vitro and to investigate whether BP can prevent steroid-induced apoptosis of articular chondrocytes. Methods: Bovine articular chondrocytes were cultured and incubated with different concentrations of clodronate, pamidronate, risedronate, or dexamethasone. In the second part of the study, BP were added to the chondrocyte cultures one hour before co-incubation with dexamethasone. Viability and proliferation were evaluated using propidium iodide staining and tritium labelled thymidine incorporation. Apoptosis was measured with annexin V staining or the TUNEL method. Results: Only high concentrations (>10(-6) mol/l) of clodronate, pamidronate, and risedronate induced a decrease in the viability and proliferation of chondrocytes. None of the BP at concentrations ranging from 10(-12) to 10(-3) mol/l induced apoptosis. Growth retardation and apoptosis induced by dexamethasone (10(-7) mol/l) was prevented by addition of pamidronate (10(-6) mol/l) or risedronate (10(-8) or 10(-6) mol/l). Conclusion: Bisphosphonates in therapeutic concentrations are safe for articular chondrocytes in vitro. Moreover, pamidronate and risedronate prevent dexamethasone-induced growth retardation and apoptosis of chondrocytes. These findings add evidence for a chondroprotective effect of nitrogen-containing BP, especially in patients treated with corticosteroids