Angelo Zoli

Serum zinc and copper in active rheumatoid arthritis: correlation with interleukin 1 beta and tumour necrosis factor alpha

Serum zinc and copper levels and serum interleukin 1β (IL1β) and tumour necrosis factor α (TNFα) levels were evaluated in 57 female patients with active rheumatoid arthritis (RA) to investigate a possible role of IL1β and TNFα on zinc and copper homeostasis in RA. Serum zinc levels were significantly lower and serum copper levels significantly higher in RA patients when compared with osteoarthritis or asymmetrical psoriatic oligoarthritis patients and with normal controls. No differences were observed in serum IgM rheumatoid factor positive and serum IgM rheumatoid factor negative patients as regards serum zinc and copper concentration. In RA patients the erythrocyte sedimentation rate and acute-phase proteins correlated negatively with serum zinc and positively with serum copper. IL1β and TNFα were found to correlate negatively with zinc and positively with copper in RA patients. Lower levels of zinc may be due to an accumulation of zinc-containing proteins in the liver and in the inflamed joints in RA. Elevated serum copper levels seem to be linked to the increased synthesis of ceruloplasmin by the liver.

Serum levels of interleukin-1b, tumour necrosis factor-a and interleukin-2 in rheumatoid arthritis. Correlation with disease activity

SummaryCytokines are potent immunoregulatory factors and may be directly involved in the disordered immunoregulation found in chronic rheumatic diseases. Interleukin-1b (IL-1b), Interleukin-2 (IL-2) and Tumour Necrosis Factor-a (TNF-a) have been implicated in the pathogenesis of rheumatoid arthritis (RA) as mediators of chronic inflammation. Serum levels of IL-1b and TNF-a measured by radioimmunoassay were significantly higher in patients with RA than in healthy controls of similar sex and age while serum levels of IL-2 were significantly lower in the same patients. Further IL-1b and TNF-a were significantly elevated in RA patients with active disease and IL-2 was significantly reduced when compared with patients with low active disease. Serum IL-1b and TNF-a appear to correlate with systemic inflammation, and systemic features of RA may result from dissemination of cytokines produced in the synovium. The role of IL-2 in RA remains controversial. Reduced levels of IL-2 may be an expression of a deficiency of T-cells to produce IL-2 in the active phases of RA or may be due to a possible absorption of IL-2 by lymphocyte receptors.

Functional, radiological and biological markers of alveolitis and infections of the lower respiratory tract in patients with systemic sclerosis

BackgroundA progressive lung disease and a worse survival have been observed in patients with systemic sclerosis and alveolitis. The objective of this study was to define the functional, radiological and biological markers of alveolitis in SSc patients.Methods100 SSc patients (76 with limited and 24 with diffuse disease) underwent a multistep assessment of cardiopulmonary system: pulmonary function tests (PFTs) every 6–12 months, echocardiography, high resolution computed tomography (HRCT) and bronchoalveolar lavage (BAL), if clinically advisable. Alveolar and interstitial scores on HRCT and IL-6 plasma levels were also assessed as lung disease activity indices.Results90 SSc patients with abnormal PFTs and 3 with signs and/or symptoms of lung involvement and normal PFTs underwent HRCT and echocardiography. HRCT revealed evidence of fibrosis in 87 (93.5%) patients, with 55 (59.1%) showing both ground glass attenuation and fibrosis. In 42 patients who had exhibited ground glass on HRCT and consented to undergo BAL, 16 (38.1%) revealed alveolitis. 12 (75%) of these patients had restrictive lung disease (p < 0.0001) and presented diffuse skin involvement (p = 0.0009). IL-6 plasma levels were higher in patients with alveolitis than in patients without (p = 0.041). On logistic regression model the best independent predictors of alveolitis were diffuse skin involvement (OR(95%CIs):12.80(2.54–64.37)) and skin score > 14 (OR(95%CIs):7.03(1.40–34.33)). The alveolar score showed a significant correlation with IL-6 plasma levels (r = 0.36, p = 0.001) and with the skin score (r = 0.33, p = 0.001). Cultures of BAL fluid resulted positive in 10 (23.8%) of the 42 patients that underwent BAL and after one year a deterioration in PFTs occurred in 8 (80%) of these patients (p = 0.01). Pulmonary artery systolic pressure ≥ 40 mmHg was found in 6 (37.5%) patients with alveolitis.ConclusionWe found alveolitis only in 38.1% of the patients who had exhibited ground glass on HRCT and then underwent BAL, probably because the concomitant fibrosis influenced results. A diffuse skin involvement and a restrictive pattern on PFTs together with ground glass on HRCT were judged possible markers of alveolitis, a BAL examination being indicated as the next step. Nevertheless BAL would be necessary to detect any infections of the lower respiratory tract that may cause further deterioration in lung function.

ACTH, Cortisol and Prolactin in Active Rheumatoid Arthritis

Abstract Prolactin (PRL) and glucocorticoids are hormones involved in the regulation of the immune system. Rheumatoid arthritis (RA) is an inflammatory condition that presents a diurnal rhythm of disease activity. ACTH, PRL, cortisol, IL-1β and TNF-α circadian rhythms have been studied in active RA (aRA) to evaluate a possible relationship between the neuroendocrine system and immunological activity in rheumatoid patients. ACTH, PRL, cortisol, PRL/cortisol ratio and IL-1β and TNF-α levels were determined in aRA patients and in control subjects at 6.00, 10.00, 14.00, 18.00, 22.00 and 02.00 h. In aRA patients we observed lower ACTH and cortisol levels at 22.00 h and 2.00 h, respectively and higher PRL and PRL/cortisol ratio at 2.00 h when compared to controls. IL-1β and TNF-α reached their highest serum levels in aRA patients at 2.00 and 6.00 h. This study provides evidence that in aRA there could be a temporary and probably causal relationship between diurnal disease activity, hormonal disequilibrium and cytokine secretion. An imbalance in favour of proinflammatory hormones (PRL and cytokines) as opposed to levels of anti-inflammatory hormones could be responsible for the diurnal rhythm of activity disease observed in aRA patients.

Intravascular tumor necrosis factor α blockade reverses endothelial dysfunction in rheumatoid arthritis

Patients with rheumatoid arthritis (RA) have endothelial dysfunction, which may predispose them to the risk of premature atherosclerosis. This study investigated the involvement of tumor necrosis factor (TNF) α in the pathophysiologic characteristics of this abnormality by use of the TNF‐α‐neutralizing antibody infliximab.

Body weight, gender and response to TNF-α blockers in axial spondyloarthritis

OBJECTIVE The objective of this study was to determine whether BMI and gender could lead to a different response rate to anti-TNF agents in patients affected by axial SpA. METHODS One hundred and seventy patients with active axial SpA (defined as a BASDAI ≥ 4) treated with an anti-TNF agent [adalimumab (ADA), etanercept (ETA), infliximab (IFX)] were retrospectively evaluated. Patients were divided according to the baseline BMI as normal weight (BMI < 25), overweight (BMI 25-30) and obese (BMI ≥ 30). After 12 months of treatment a 50% improvement of the initial BASDAI (BASDAI50) was the primary end point and BASDAI ≤ 1 was the secondary end point. RESULTS After 12 months of anti-TNF treatment, 67.8% of men and 46.2% of women reached the BASDAI50 (P = 0.01). According to BMI categories, the rate of BASDAI50 achievement decreased from 72.8% in normal weight subjects to 54.5% in overweight and 30.4% in obese subjects (P < 0.001). In the logistic regression analysis, the best independent predictors of failure to obtain a BASDAI50 response at the 12th month of therapy in axial SpA patients were female gender [odds ratio (OR) 3.23 (95% CI 1.52, 7.14)] and a BMI ≥ 30 [OR 3.57 (95% CI 1.15, 11.11)]. Analysing outcomes based on IFX therapy (the larger subgroup), the BASDAI50 response rate fell from 79.0% in normal weight subjects to 56.7% in overweight and 16.7% in obese subjects (P < 0.001). No significant differences were observed with ADA and ETA. CONCLUSION Data suggest that being female, overweight and mostly obese is associated with a lower rate of success in obtaining response status in axial SpA patients treated with anti-TNF drugs. Body weight could represent a modifiable factor to reach the best outcome in axial SpA patients treated with TNF blockers.

A study of serum androgen and cortisol levels in female patients with rheumatoid arthritis. Correlation with disease activity

SummaryAndrogen status and the role played by androgens in the pathogenesis of rheumatoid arthritis (RA) in female patients are a matter of debate. In the present study serum testosterone (T), DHEAS, sex hormone binding globulin (SHBG) and cortisol levels were determined in 55 RA women, both in pre- and post-menopausal (M) status, and in a group of healthy subjects. Patients were divided into two groups according to disease activity and a correlation analysis of hormonal levels against serum IL1β levels was performed. No significant differences were found in serum T levels between RA patients and controls, both in preM (1.38±0.4 vs 1.35±0.3 nmol/l; p=ns) and in postM status (1.21±0.2 vs 1.10±0.2 nmol/l; p=ns). Serum SHBG levels were lower in RA patients than in control subjects, both in pre and in postM status. DHEAS levels were significantly lower in preM RA patients than in controls (2.34±1.2 vs 5.93±1.6 µmol/l; p<0.001) while cortisol levels were significantly higher in preM active RA patients than in controls (466.2±30.3 vs 411±66.2 nmol/l; p=0.02). IL1β levels were significantly higher in RA patients than in controls both in pre- and postM subjects (70±33.8 vs 23.1±2.9 and 92±27.4 vs 31.9±3.1 fmol/l, p<0.001, respectively).Although androgen status could play a role in the pathogenesis of RA, at present it is not possible to exclude the influence of RA itself on sex hormone profile.

Influence of diet with different lipid composition on neutrophil chemiluminescence and disease activity in patients with rheumatoid arthritis.

Neutrophil chemiluminescence was determined in patients with active rheumatoid arthritis. Twelve patients were randomly assigned either to a diet high in polyunsaturated fatty acids supplemented with eicosapentaenoic and docosahexaenoic acids or to a diet high in saturated fatty acids. A correlation with clinical and laboratory parameters is also reported. No statistical difference was observed in neutrophil chemiluminescence and in clinical parameters in the group of patients treated with a diet high in saturated fatty acids. Fish oil ingestion resulted in subjective alleviation of active rheumatoid arthritis and reduction of neutrophil chemiluminescence. This study corroborates the hypothesis of an anti-inflammatory role for polyunsaturated fatty acids in patients with chronic inflammatory diseases.

Osteoporosis and bone metabolism in postmenopausal women with osteoarthritis of the hand.

Objective: Osteoarthritis and osteoporosis are two major health problems affecting postmenopausal women. Epidemiological observations seem to demonstrate a possible inverse relationship between osteoarthritis and osteoporosis. Erosive osteoarthritis (EOA) of the hand is a destructive form of primary osteoarthritis. This study evaluated bone mineral density and bone metabolism changes in erosive and nonerosive hand osteoarthritis women. Design: Fifty-five women (mean age, 59 years; body mass index, 23 ± 1.4 kg/m2) who had been postmenopausal for an average of 9 years and who presented with hand osteoarthritis according to American College of Rheumatology criteria were enrolled in the study; 15 women showed clinical and radiological evidence of hand EOA. Twenty women matched for age, age at menopause, and body mass index formed the control group. Bone mineral density (g/cm2) was measured at the hip and lumbar spine using dual-energy x-ray absorptiometry. Serum and urinary calcium and phosphate, serum 25-hydroxyvitamin D, parathyroid hormone, osteocalcin, and urinary breakdown products of bone matrix (CrossLaps) were analyzed. Results: Women with hand EOA had a statistically significant lower T- and Z-score L2-L4 value than non-hand EOA women and controls (P < 0.01). Moreover, postmenopausal women with hand EOA had higher significant percentage of osteoporosis at lumbar spine when compared with non-hand EOA postmenopausal women and controls. Any statistically significant difference in osteocalcin and CrossLaps serum levels was noted among women with hand EOA, hand osteoarthritis, and controls. Conclusions: Our data suggest that postmenopausal women with clinical and radiological EOA are at risk for development of osteoporosis.

ACR70-disease activity score remission achievement from switches between all the available biological agents in rheumatoid arthritis: a systematic review of the literature.

IntroductionThe aim of our analysis was to compare the gaining of a major response (disease activity score [DAS] remission or American College of Rheumatology 70% improvement criteria [ACR70]) by switching between all the available biological therapies in rheumatoid arthritis.MethodsA systematic review was performed including studies, published before December 2008, in which a second biological agent was used and clinical outcomes were evaluated after a first biological failure.ResultsNine articles were included. Switching from etanercept and/or infliximab to adalimumab is effective with an ACR70 response ranging from 5% to 33%. Rituximab may be slightly more effective than switching to a second anti-tumor necrosis factor-alpha (anti-TNFα), reaching an ACR70 or DAS remission response in 12% and 9%, respectively. Clinical trials confirmed the efficacy in switching to abatacept (gain of effect 10.2%). Tocilizumab allows DAS28 (DAS using 28 joint counts) remission in 30.1% but ACR70 only in 12.4% of patients refractory to anti-TNFα.ConclusionsThe efficacy of a second biological agent, irrespective of the mode of action, in reaching an ACR70 or DAS remission after a first biologic is observed from 5% to 15% and from 9% to 15.4%, respectively (except in two studies).