Rheumatoid Arthritis: de Portu S

Turiel M, Atzeni F, Tomasoni L, de Portu S, Delfino L, Bodini BD, Longhi M, Sitia S, Bianchi M, Ferrario P, Doria A, De Gennaro Colonna V, Sarzi-Puttini P. · Department of Health Technologies, Cardiology Unit, IRCCS Orthopedic Galeazzi Institute, University of Milan, Milano, Italy. · Rheumatology (Oxford). · Pubmed #19465588 No free full text.

Abstract: OBJECTIVE: Plasma concentration of asymmetric dimethylarginine (ADMA), a major endogenous inhibitor of nitric oxide synthase, is considered a novel risk factor for endothelial dysfunction associated with enhanced atherosclerosis. Coronary microcirculation abnormalities have been demonstrated in patients with early rheumatoid arthritis (ERA) without any signs or symptoms of coronary artery disease (CAD). The aim of the study was to compare the ERA and control groups with ADMA, intima-media thickness (IMT) and coronary flow reserve (CFR) levels. It assessed whether ERA patients have more cardiovascular risk (endothelial dysfunction and coronary microvascular abnormalities), and evaluated whether any difference in IMT/CFR between ERA and controls can be explained by any difference in ADMA levels between the groups. METHODS: The study involved 25 ERA patients (female/male 21/4; mean age 52.04 +/- 14.05 years; disease duration <or=12 months) and 25 healthy volunteers with no history or current signs of CAD or other traditional risk factors. Dipyridamole trans-thoracic stress echocardiography was preformed to evaluate CFR, and carotid ultrasound to measure the IMT of the common carotid arteries. Blood samples were obtained in order to assess ADMA levels before the patients had received any biological or non-biological DMARDs, or steroid therapy. RESULTS: CFR was significantly reduced in the ERA patients (2.5 +/- 0.5 vs 3.5 +/- 0.8; P <0.01). In particular, 6/25 (24%) had a CFR of <2 consistent with potentially dangerous coronary flow impairment. Common carotid IMT was significantly greater in the ERA patients, although still within the normal range (0.68 +/- 0.1 vs 0.56 +/- 0.11 mm; P <0.01). There was a significant correlation between CFR and plasma ADMA levels in the ERA population (r = -0.53; P <0.01). IMT was negatively associated with CFR (P <0.05). CONCLUSIONS: Plasma ADMA levels were significantly higher in the ERA patients. A statistically significant negative effect of ADMA levels on CFR value was observed. The effect of ADMA levels on IMT is not significant.

Sarzi-Puttini P, Atzeni F, Di Franco M, Lama N, Batticciotto A, Iannuccelli C, Dell'Acqua D, de Portu S, Riccieri V, Carrabba M, Buskila D, Doria A, Valesini G. · Rheumatology Unit, L. Sacco University Hospital, Milan, Italy. · Autoimmunity. · Pubmed #18176867 No free full text.

Abstract: OBJECTIVE: To investigate the prevalence of antipolymer antibody (APA) in patients with fibromyalgia (FM) and to examine its association with FM severity symptoms. METHODS: The study population consisted of 79 FM patients and 75 controls: 32 with psoriatic arthritis and 43 with rheumatoid arthritis APA levels were indirectly assayed using a commercial ELISA kit from Corgenix (Westmister, Colorado, USA). Optical density (OD) values were recorded on duplicates of each of the reference and patient samples. Among clinical variables we investigated pain, measured according to visual analog scales (VAS: 0-100), fatigue, stiffness, anxiety, depression, all measured by VAS (0-100), and health status measured by Fibromyalgia Impact Questionnaire (FIQ). RESULTS: Sixteen of the 79 FM patients (20.3%) and 12/78 controls (15.4%) were positive for APAs (P = 0.536). Following ROC analysis, area under curve (AUC) was 0.49 (95% CI: 0.40, 0.58). Focusing on FM patients, we observed a correlation between APA titre and pain (tau: - 0.221; P = 0.020) and fatigue (tau: - 0.205; P = 0.032) at univariate analysis. Binomial regression analysis, controlling for clinical and demographic variables, showed that pain (PPR: 0.923; P = 0.007) and fatigue (PPR: 0.948; P = 0.024) were significantly associated with APA test sensitivity. CONCLUSIONS: APA test exhibited a low sensitivity in FM patients and it did not distinguish this group of patients from the controls enrolled in this study. Interestingly, positive APA test prevalence increased with less severe pain or fatigue.

Atzeni F, Sarzi-Puttini P, Dell' Acqua D, de Portu S, Cecchini G, Cruini C, Carrabba M, Meroni PL. · Rheumatology Unit, Department of Medicine, L Sacco University Hospital, 74 Via GB Grassi, 20157 Milano, Italy. · Arthritis Res Ther. · Pubmed #16356192 links to  free full text

Abstract: Studies on autoantibody production in patients treated with tumor necrosis factor-alpha (TNF-alpha) inhibitors reported contradictory results. We investigated in a prospective study the efficacy of a treatment with human monoclonal anti-TNF-alpha antibody (adalimumab) in patients with rheumatoid arthritis (RA) and we evaluated the relationship between treatment efficacy and the incidence and titers of disease-associated and non-organ-specific autoantibodies. Fifty-seven patients with RA not responsive to methotrexate and treated with adalimumab were enrolled. Antinuclear, anti-double-stranded(ds)DNA, anti-extractable nuclear antigens, anti-cardiolipin (aCL), anti-beta2 glycoprotein I (anti-beta2GPI) autoantibodies, rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) autoantibodies were investigated at baseline and after 6 and 12 months of follow-up. Comparable parameters were evaluated in a further 55 patients treated with methotrexate only. Treatment with adalimumab induced a significant decrease in RF and anti-CCP serum levels, and the decrease in antibody titers correlated with the clinical response to the therapy. A significant induction of antinuclear autoantibodies (ANA) and IgG/IgM anti-dsDNA autoantibodies were also found in 28% and 14.6% patients, respectively, whereas aCL and anti-beta2GPI autoantibodies were not detected in significant quantities. No association between ANA, anti-dsDNA, aCL and anti-beta2GPI autoantibodies and clinical manifestations was found. Clinical efficacy of adalimumab is associated with the decrease in RF and anti-CCP serum levels that was detected after 24 weeks and remained stable until the 48th week of treatment. Antinuclear and anti-dsDNA autoantibodies, but not anti-phospholipid autoantibodies, can be induced by adalimumab but to a lower extent than in studies with other anti-TNF blocking agents.