Agonistic anti-human Fas monoclonal antibody induces fibroblast-like synoviocyte apoptosis in haemophilic arthropathy: potential therapeutic implications.

Haemophilic arthropathy (HA) is characterized by chronic proliferative synovitis leading to cartilage destruction and shares some pathological features with rheumatoid arthritis (RA). Apoptosis has been implicated in RA pathogenesis, and an agonistic anti-Fas monoclonal antibody (mAb) was found to induce RA fibroblast-like synoviocyte (FLS) apoptosis and suppress synovial hyperplasia in animal models of RA. The aim of this study was to evaluate the effect of anti-Fas mAb on HA-FLS. FLS were isolated from knee synovial biopsies from six HA patients, six RA patients and six healthy subjects. The expression of Fas in synovial biopsies was investigated by immunohistochemistry. FLS were stimulated with anti-Fas mAb at different concentrations, alone or in combination with tumour necrosis factor-α (TNF-α) and basic fibroblast growth factor (bFGF). Fas expression in FLS was assessed by Western blot. Cell viability was studied with the WST-1 assay. Active caspase-3 levels were measured using ELISA and Western blot. A strong Fas-immunoreactivity was observed in different cells of HA synovium, including FLS, inflammatory cells and endothelial cells. Fas antigen was constitutively overexpressed in cultured HA-FLS. Anti-Fas mAb had a significant cytotoxicity on HA-FLS in a dose-dependent manner, either alone or in combination with TNF-α and bFGF. These cytotoxic effects were due to the ability of anti-Fas to induce HA-FLS apoptosis, as shown by the increased active caspase-3 levels. Anti-Fas mAb exhibited a more pronounced pro-apoptotic effect on HA-FLS than RA-FLS. Fas antigen is highly expressed on HA-FLS and its stimulation by anti-Fas mAb may be an effective strategy to induce HA-FLS apoptosis.

Hypovitaminosis D and osteopenia/osteoporosis in a haemophilia population: a study in HCV/HIV or HCV infected patients.

Recent reports show a correlation between haemophilia and osteoporosis. HIV, HCV and their treatments are independently associated with an increased risk of osteoporosis. Vitamin D plays a pivotal role in bone mineralization. The aim of our study was to compare Vitamin D levels, bone metabolism markers and bone mineral density (BMD) in patients with haemophilia with or without co-infections. Seventy-eight adult patients with severe or moderate haemophilia A or B were subdivided into three groups of 26 patients each (HIV-HCV co-infected, HCV mono-infected and uninfected). The BMD was measured by dual energy X-ray absorptiometry (DXA) at both the femoral area (F) and lumbar spine (L). This was correlated to laboratory values and haemophilic arthropathy was assessed using validated clinical and radiological scores. The DXA showed a homogeneous F-BMD reduction in all the three groups, whereas L-BMD was significantly lower in co-infected patients (P < 0.05). The clinical score was higher in co-infected (P < 0.002) and mono-infected (P < 0.006). The radiological score was higher in mono-infected than in the other two groups (P < 0.001). Overall 25-hydroxyvitamin D (25-OH Vit D) was reduced (87%). Bone-specific alkaline phosphatase (b-ALP) and telopeptide were increased in co-infected (P < 0.001 and P < 0.01) and mono-infected (P < 0.001 and P < 0.02). The result of the homogeneous F-BMD reduction in all groups could be explained by the pivotal role of arthropathy; the lower L-BMD in co-infected and the increase of b-ALP and telopeptide in co-infected and mono-infected groups suggest faster bone metabolism in case of infections.

Ultrasound detects joint damage and bleeding in haemophilic arthropathy: a proposal of a score.

Haemarthrosis triggers haemophilic arthropathy (HA) because bleeding starts synovitis immediately, damages cartilage and leads to loss of function and disability. The aim of our study was to investigate the capacity of ultrasonography (US) in detecting bleeding and joint damage in HA. The joints of 62 patients (pts) with haemophilia A or haemophilia B were consecutively evaluated and scored (score ranging from 0 to 21) for effusion (E), bone remodelling (BR), cartilage damage (CD), synovial hypertrophy (SH), haemosiderin (H), osteophytes (O), haemarthrosis (Hae), erosion (Er) and fibrotic septa (FS) with US. X-rays [Pettersson Score (PXS)] were performed in 61 patients and clinical evaluation [World Federation Haemophiliac orthopaedic score (WFHO)] was performed in all patients. A total of 20 healthy subjects and 20 patients affected by Rheumatoid Arthritis (RA) were used as controls. Power Doppler US (PDUS) was performed in all patients on the knee, ankle and elbow joints. A total of 83 joints were studied (50 knees; 12 elbows and 21 ankles). US showed effusion in 57 joint, bone remodelling in 62, cartilage damage in 64, synovial hypertrophy in 45, haemosiderin in 39, osteophytes in 30, haemarthrosis in 24, erosion in 5 and fibrotic septa in 3. The X-rays score showed remodelling in 47 joints, narrowing joint space in 44, displacement/angulation in 39, osteoporosis in 42, subchondral irregularity in 44, subchondral cyst formation in 37, osteophytes in 36 and erosions in 25. The US score in healthy subjects was always ≤ 5 (range 0 to 4). In haemophiliacs, 34 of 83 joints showed US score ≤ 5, and 49 US score > 5. Joints with US score ≤ 5 had a low PXS (SRCC = 0.375, P < 0.01) and joints with US score > 5 showed a high PXS (SRCC = 0.440, P < 0.01). A significant correlation between US score and PXS for bone remodelling [Spearman's rho Correlation Coefficient (SRCC) = 0.429, P < 0.01] and for osteophytes (SRCC = 0.308, P < 0.05) was found. The correlation between the US score and number of bleedings in 83 joints was very significant (SRCC = 0.375, P < 0.01). A total of 24 bleeding joints were identified and verified with aspiration of haematic fluid. US may detect bone and cartilage alterations and synovitis. Indeed, PDUS identified bleeding also in asymptomatic joints and was able to show different entity of haemarthrosis. US may be a feasible and reliable tool to evaluate joint modifications in HA.

Critical US visibility with tissue harmonic imaging of subcutaneous nodules().

INTRODUCTION: Assessment of US ability to identify subcutaneous nodular lesions using conventional B mode imaging (CBMI) and tissue second harmonic imaging (THI). MATERIALS AND METHODS: Three different types of equipment were used (Philips Envisor HDC, Philips HD 11 XE and GE Logic E) with 12-13 MHz probes and THI probes with variable frequency. One experienced operator studied 31 patients (24 women, 7 men, mean age 49 ± 15) with 52 subcutaneous nodular lesions of which 43 were palpable and 9 were nonpalpable. Statistical analysis was carried out using chi-square test. RESULTS: 19/52 subcutaneous nodular lesions were hyperechoic, 10/52 were isoechoic and 23/52 were hypoechoic. Of the hyperechoic nodules, 8/19 (42%) (p < 0.005) were not detected using THI, as they "disappeared" when THI was activated. Of the isoechoic nodules only 1/10 was not detected using THI, and of the hypoechoic nodules only 2/23 were not detected. Of the nodular lesions detected using CBMI and also using THI (41/52), 16/41 were shown more clearly using THI than using BMCI. No nodule was detected with the exclusive use of THI. CONCLUSIONS: The statistical significance of the "disappearing" lesions (p < 0.005), mainly hyperechoic (42%), at the activation of THI must lead to a reconsideration of routine activation of THI during the entire US examination in the evaluation of subcutaneous lesions in order to avoid the risk of missing important lesions. The present results suggest that both BMCI and THI should be used in the study of subcutaneous lesions.

Early detection of median nerve syndrome at the carpal tunnel with high-resolution 18 MHz ultrasonography in systemic sclerosis patients.

OBJECTIVES: To investigate carpal tunnel syndrome (CTS) with ultrasound (US) in asymptomatic SSc patients and to seek out the relationship between CTS and SSc clinical variables METHODS: In 64 SSc patients (55 women and 9 men, mean age 57±14 years) and in 30 healthy controls, area (MNA), transverse (MNT) and anteroposterior (MNAP) diameters of MN at carpal tunnel were studied with US (My Lab 25 XVG US Esaote 18 MHz). MN flattening ratio (MNFR) was calculated. Duration of disease, subset (limited, diffuse), phase of skin involvement (oedematous, atrophic, fibrotic), modified Rodnan skin score (mRSS) and friction tendon rub were also recorded. RESULTS: MNA (p<0.001), MNT (p<0.005) and MNFR (p<0.005) were significantly higher in the SSc patients than in controls, while no difference in MNAP was found. There was no correlation between median nerve (MN) and SSc clinical features (only lower MNAP correlated inversely with longer disease duration; Spearman coefficient -0.2). CONCLUSIONS: MN involvement is frequently present in all phases of asymptomatic SSc patients, independently to clinical variables.

Sonographic evaluation of the temporomandibular joints in juvenile idiopathic arthritis().

INTRODUCTION: Juvenile idiopathic arthritis (JIA) may cause damage to the temporomandibular joint (TMJ). In oligoarticular forms of JIA, TMJ involvement is often asymptomatic and consequently overlooked. The aim of this study was to evaluate the presence of TMJ joint effusion (JE) by ultrasonography (US) in patients with early arthritis. MATERIALS AND METHODS: We examined 68 children (57 girls, 11 boys, age range 9.1-16.0 years, mean age 11.0 years) recently diagnosed with JIA. None had received any specific treatment for inflammation. Symptomatic TMJ involvement was diagnosed when one or more of the following were present: 1) recurrent pain (spontaneous or on movement of the jaw); 2) crepitation; 3) feeling of stiffness or fatigue of the jaw; 4) intermittent locking. US of the TMJ was performed in static and dynamic phases with a General Electric LOGIQ7 scanner and a linear transducer (8.5 MHz) positioned along the axis of the mandibular ramus. JE was diagnosed when the joint capsule was ≥1.5 mm thick. RESULTS: Forty-six out (68%) of 68 children had US evidence of TMJ effusions (bilateral in 16 [35%] cases), but only 2/46 were symptomatic. CONCLUSIONS: These data suggest that children with early stage oligoarticular JIA children are likely to have inflammation of the TMJs even in the absence of symptoms. US is a simple-to-use, noninvasive, radiation-free tool that can provide useful information in the assessment and follow-up of TMJ involvement in children and young adults with JIA.

QuantiFERON-TB Gold and the TST are both useful for latent tuberculosis infection screening in autoimmune diseases.

Screening for active tuberculosis (TB) and latent TB infection (LTBI) is mandatory prior to the initiation of tumour necrosis factor-alpha inhibitor therapy. However, no agreement exists on the best strategy for detecting LTBI in this population. The aim of the present study was to analyse the performance of the tuberculin skin test (TST) and QuantiFERON-TB Gold in-tube (QFT-GIT) on LTBI detection in subjects with immunomediated inflammatory diseases (IMID). The TST and QFT-GIT were prospectively performed in 398 consecutive IMID subjects, 310 (78%) on immunosuppressive therapy and only 16 (4%) had been bacillus Calmette-Guérin (BCG) vaccinated. Indeterminate results to QFT-GIT were found in five (1.2%) subjects. Overall, 74 (19%) out of 393 subjects were TST-positive and 52 (13%) were QFT-GIT-positive. Concordance between TST and QFT-GIT results was good (87.7%): 13 were QFT-GIT-positive/TST-negative and 35 QFT-GIT-negative/TST-positive. By multivariate analysis both tests were significantly associated with older age. Only the TST was associated with BCG vaccination and radiological lesions of past TB. Use of immunosuppressive drugs differently modulated QFT-GIT or TST scoring. Use of the QuantiFERON-TB Gold in-tube, as a screening tool for latent tuberculosis among immunomediated inflammatory disease subjects, is feasible. Until further data will elucidate discordant tuberculin skin test/QuantiFERON-TB Gold in-tube results, a strategy of simultaneous tuberculin skin and QuantiFERON-TB Gold in-tube testing in a low prevalence bacillus Calmette-Guérin vaccinated population, should maximise potentials of latent tuberculosis diagnosis.

Intravenous immunoglobulins improve the function and ameliorate joint involvement in systemic sclerosis: a pilot study.

BACKGROUND: In systemic sclerosis (SSc), joint involvement may reduce the functional capacity of the hands. Intravenous immunoglobulins have previously been shown to benefit patients with SSc. AIM: To verify the efficacy of intravenous immunoglobulins on joint involvement and function in SSc. PATIENTS AND METHODS: 7 women with SSc, 5 with limited and 2 with diffuse SSc, with a severe and refractory joint involvement were enrolled in the study. Methotrexate and cyclophosphamide pulse therapy did not ameliorate joint symptoms. Hence, intravenous immunoglobulins therapy was prescribed at a dosage of 2 g/kg body weight during 4 days/month for six consecutive courses. The presence of joint tenderness and swelling, and articular deformities (due to primary joint involvement and not due to skin and subcutaneous changes) were evaluated. Before and after 6 months of treatment, patients were subjected to (1) Ritchie Index (RI) evaluation of joint involvement; (2) Dreiser Algo-Functional Index (IAFD) evaluation of hand joint function; (3) pain visual analogue scale (VAS) to measure joint pain; (4) Health Assessment Questionnaire (HAQ) to evaluate the limitations in everyday living and physical disability; and (5) modified Rodnan Skin Score for skin involvement. RESULTS: After 6 months of intravenous immunoglobulins therapy, joint pain and tenderness, measured with the VAS, decreased significantly (p<0.03), and hand function (IAFD) improved significantly (p<0.02), together with the quality of life (HAQ; p<0.03). All patients significantly improved, except for one. The skin score after 6 months of intravenous immunoglobulins therapy was significantly reduced (p<0.003). CONCLUSION: This pilot study suggests that intravenous immunoglobulins may reduce joint pain and tenderness, with a significant recovery of joint function in patients with SSc with severe and refractory joint involvement. The cost of intravenous immunoglobulins might limit their use only to patients who failed disease-modifying antirheumatic drugs.

Angiotensin-converting enzyme I/D polymorphism and macrovascular disease in systemic sclerosis.

OBJECTIVE: Systemic sclerosis (SSc) is characterized by microvascular and macrovascular alterations. The D allele of the ACE I/D polymorphism is known to be associated with an increased incidence of atherosclerosis and has been recently proposed as associated with increased risk of SSc. This study evaluates the relationship between intima-media thickness (IMT), ankle-brachial pressure measurements (ABPI) and ACE I/D polymorphism in SSc patients. METHODS: According to the presence of ACE D allele (analysed by PCR), 53 SSc patients (47 females and 6 males; median age was 60.4 +/- 10.68 yrs; range 40-75 yrs) were divided in carriers of the D allele (DD + ID) (n = 46) and carriers of the I allele (II) (n = 7). In these patients, IMT and ABPI [calculated as the posterior tibial artery pressure (mmHg) divided by the brachial pressure] were obtained. Forty-three healthy controls (40 women and 13 men; median age 56.3 +/- 10.23; range 40-70 yrs) of the same ethnicity were recruited. RESULTS: SSc patients had IMT significantly higher than controls (0.85 +/- 0.03 vs 0. 68 +/- 0.01; P < 0.03). No significant differences (P > 0.3) in ABPI values between patients (1.018 +/- 0.10) and controls (1.091 +/- 0.11) were found. SSc patients with ACE DD and ID genotype showed an IMT significantly greater (0.89 +/- 0.03) than those carrying the II genotype (0.61 +/- 0.01) (P < 0.04). ABPI was not different among ACE gene genotypes. CONCLUSION: Our findings confirm an increased prevalence of macrovascular disease in SSc patients and show that IMT is greater in patients carrying the ACE DD and ID genotype in comparison with II homozygotes. This suggests that, in SSc, the presence of ACE D allele may predispose to an involvement of the macrovascular system.

Etrurians vs Greeks: May ACE I/D polymorphism still be considered as a marker of susceptibility to SSc?

OBJECTIVE: SSc is characterized by immune dysfunction and microvascular involvement. A different genetic background may determine a different polymorphic allele frequency between different populations, and data from literature reported conflicting results about the role of genetic components in predisposing to the disease. We carried out this study in order to compare the ACE I/D polymorphism genotype distribution and alleles frequency in two different populations from the Mediterranean area. METHODS: Forty-eight Italian and 41 Greek SSc patients compared with 112 Italian and 93 Greek controls, have been studied. The ACE I/D polymorphism has been analysed. RESULTS: The genotype distribution and allele frequency were in Hardy-Weinberg equilibrium for Italian and Greek SSc patients and controls. Among the Italian patients a significantly higher ACE D allele frequency than in the controls was found, whereas among the Greeks a higher prevalence was observed in the healthy subjects. A significant difference in ACE D allele frequency between Italian and Greek controls was observed (p = 0.04). ACE D allele was associated to the predisposition to SSc in Italians, but not in Greeks. CONCLUSION: We confirm that Italian SSc patients have a higher ACE D allele frequency that is not present in the Greek patients. Thus, the two populations living in different Mediterranean areas and resulting from the Mediterranean civilization, do not show the same ACE-gene related allele frequencies. Other populations of the Mediterranean area must be investigated by using unlinked genetic markers to verify the homogeneity of the genetic background, and to test for a "true" difference in their ethnic origin.

Comparison of ultrasonography and magnetic resonance imaging in the evaluation of temporomandibular joint disc displacement.

The aim of this work was to evaluate the accuracy and reliability of ultrasonography in the diagnosis of temporomandibular joint (TMJ) disc position abnormalities compared with magnetic resonance imaging (MRI). Participants in this study were 41 consecutive patients with signs and symptoms of temporomandibular disorders. All 82 TMJs were evaluated to detect disc position abnormalities by means of ultrasonography and MRI, performed by blinded operators. The accuracy of ultrasonography was evaluated with respect to MRI. Ultrasonography demonstrated good accuracy in the evaluation of disc position, showing a sensitivity of 65.8% and a specificity of 80.4%, resulting in a positive likelihood ratio of 3.35, a negative likelihood ratio of 0.42, and a diagnostic odds ratio of 7.97. The predictive positive and negatives values were respectively 77.1% and 70.2% and the overall agreement between the two radiological techniques was 73.1%. Ultrasonography proved to be accurate in detecting normal disc position and the presence of abnormalities in disc-condyle relationship but not so useful for the distinction between disc displacement with and without reduction.

[Peripheral nervous system in limited systemic sclerosis]. / Il sistema nervoso periferico nella sclerosi sistemica limitata.

OBJECTIVES: PNS is involved in Systemic Sclerosis (SSc) since the earliest phases. Our aim is to perform an ultrastructural study on skin PNS fibers in SSc. METHODS: Skin biopsies were taken from forearms of 8 patients affected by limited SSc (lSSc) and 3 controls and processed for transmission electron microscopy (TEM). The semithin sections (2 mm) were observed at light microscope and optical fields were chosen for ultrathin sections (1 mm) preparation and TEM examination. RESULTS: In lSSc skin, in the semithin sections, damaged areas are close to apparently spared areas. At TEM, in early lSSc patients, signs of inflammation and damaged microvessels are visible in derma. PNS fibers are no damaged. In advanced lSSc, fibrosis prevails on inflammation, and slight ultrastructural alterations of PNS fibers are evident in papillar derma. CONCLUSIONS: PNS lesions are different in severity in lSSc according to the disease duration, resulting more severe in advanced than in early phase.

Ultrasonographic vs magnetic resonance imaging findings of temporomandibular joint effusion.

AIM: The aim of this study was to assess the accuracy of ultrasonography (US) in the evaluation of temporomandibular joint (TMJ) effusion compared with magnetic resonance imaging (MRI) findings, assumed as the gold standard. METHODS: The study group consisted of 44 patients with signs and symptoms of temporomandibular disorders (TMD). Each joint (N=88) was evaluated using US and magnetic resonance (MR) to detect the presence of effusion. The 2 examinations were carried out by 2 blinded operators within no more than 2 weeks from each other. During that period the patients did not receive any kind of treatment. Sensitivity, specificity, positive predictive values (PPV) and negative predective values (NPV) of US were calculated. The agreement between the 2 diagnostic techniques was then evaluated by Cohen's K test. RESULTS: MRI depicted intra-articular effusion in 41 of the 88 TMJs (46.5%) while no effusion was detected in the remaining 47 joints (53.5%). Ultrasonographic imaging revealed effusion in 42/88 joints (47.8%), while the remaining 46 joints (52.2%) showed no effusion. US showed a sensitivity of 75.6% and a specificity of 76.5%. The PPV and NPV were 73.8% and 78.2% respectively. US vs MRI agreement for the diagnosis of TMJ effusion was fairly good (pct. agreement 76.1%; K=0.521). CONCLUSION: US is a low-cost, easy-performing, non-invasive, rapidly-executing imaging technique whose possible employ in the study of the TMJ is very promising.

The role of ultrasonography in the diagnosis of temporomandibular joint disc displacement and intra-articular effusion.

AIM: The aim of this work is to conduct a preliminary study to investigate the usefulness of ultrasonography (US) in the study of temporomandibular joint (TMJ), comparing ultrasonographic diagnosis of joint effusion and disc displacement with those based on an accurate clinical examination. METHODS: Participants in this study were 47 consecutive patients complaining for TMJ problems. All 94 TMJs were evaluated to detect the presence of intra-articular effusion and disc displacement by means of 2 diagnostic instruments: a standardized clinical assessment based on the Research Diagnostic Criteria for Temporomandibular Disorders (RDC-TMD) at the Section of Prosthetic Dentistry, and an ultrasonographic investigation conducted by a blinded operator at the Operative Unit of the Department of Rheumatology, Univesity of Pisa, Italy. Agreement between the two diagnostic techniques has been evaluated by means of Cohen's K test. RESULTS: Ultrasonography showed a good agreement with clinical assessment for the diagnosis of both intra-articular effusion (percentage of agreement 80%; K=0.611) and disc displacement (agreement 81.9%; K=0.572). CONCLUSION: When compared to a standardized clinical assessment, ultrasonographic technique showed a good diagnostic capability to detect TMJ intra-articular effusion and disc displacement. Within all the limitations of this study, it can be suggested that ultrasonography could represent a promising imaging technique in the study of temporomandibular joint.

A comparison of ultrasonography and magnetic resonance imaging in the evaluation of temporomandibular joint involvement in rheumatoid arthritis and psoriatic arthritis.

OBJECTIVE: To define the diagnostic value of ultrasonographic (US) examination in comparison with magnetic resonance imaging (MRI) for the assessment of temporomandibular joint (TMJ) involvement in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). METHODS: MRI and US examinations were performed in 33 patients (22 with RA and 11 with PsA). Alterations of the disc, alterations of the condyle and joint effusion were evaluated. RESULTS: Pathological changes of the TMJ were observed by MRI in 24 patients and by US in 31 patients. The sensitivity and specificity of US were calculated in comparison with MRI. The sensitivity was 72.2% and the specificity was 60% in the assessment of pathological changes of the TMJ. The sensitivity was 69.6% with specificity of 30.0% in the assessment of alterations of the disc; the sensitivity was 70.6% with specificity of 75.0% in the assessment of joint effusion. Significant concordance was not observed in the assessment of condylar alterations. CONCLUSIONS: US imaging appears able to detect different pathological changes of the TMJ and may be considered an important diagnostic tool for clinical evaluation of the TMJ in RA and PsA.

Ultrasound assessment of increased capsular width as a predictor of temporomandibular joint effusion.

OBJECTIVES: The aim of this study was to evaluate whether an increased capsular width evidenced by ultrasound (US) could be an indirect marker of temporomandibular joint (TMJ) effusion. METHODS: 138 TMJs were evaluated by US and magnetic resonance imaging (MRI) by two blinded calibrated investigators. US measures of capsular width (in mm) and MRI diagnosis of TMJ effusion (presence/absence) were used to perform a receiver operating characteristic (ROC) curve analysis in order to assess the most accurate cut-off value of capsular width that was able to discriminate between joints with and without MRI effusion. RESULTS: Diagnostic accuracy of US to detect MRI-depicted TMJ effusion was good (area under the ROC curve=0.817). US sensitivity was high for values below the cut-off value of 1.950 mm (true positive rate (TPR)=83.9%; false positive rate (FPR)=26.3%), while specificity was high for values above the cut-off value of 2.150 mm (TPR=71.0%; FPR=11.8%). CONCLUSIONS: Analysis of ROC curve appears to reveal that the critical area is around the 2 mm value for TMJ capsular width. These findings need to be refined by further studies assessing the smallest detectable difference in capsular width, with attention to reliability of interobserver observations.

Impaired glutathione reductase activity and levels of collagenase and elastase in synovial fluid in rheumatoid arthritis.

OBJECTIVE: To test the activity of elastase, collagenase and glutathione reductase in the synovial fluid (SF) of patients with rheumatoid arthritis (RA) and in patients with osteoarthritis (OA); to correlate the elastase and collagenase activity with the glutathione reductase activity, which is important for the inactivation of oxygen free radicals. METHODS: 24 patients affected by osteoarthrosis and 24 patients affected by rheumatoid arthritis took part in the study. We measured elastase activity towards the substrate metoxysuccinyl-alanyl-alanyl-prolyl-valyl-p-nitroanilide (MeOSuc-ala-ala-proval-p-NA) which is highly specific for elastase, and insensitive to the other serine proteases, such as cathepsin G; collagenase activity was measured using [14C]-acetylated collagen as the substrate. Glutathione reductase activity was measured following the oxidation of nicotinamide adenine dinucleotide phosphate reduced (NADPH) in the presence of oxidized glutathione (GSSG). RESULTS: The concentrations of elastase, collagenase and glutathione reductase were statistically higher in patients with RA than in patients with OA. Moreover, in the SF of patients with RA we found positive correlation between enzyme activity levels. CONCLUSION: These results confirm a high activity of collagenase and elastase in the SF of patients with RA, which is about 30 times higher than that found in the SF of patients with OA. These data underline the synergic action of these enzymes in the pathogenesis of joint damage. RA patients also exhibit higher levels of glutathione reductase, which is important for the detoxification pathway of oxygen free radicals. However, compared with findings for collagenase and elastase, the increase in glutathione reductase is only three times higher than level found in the SF of OA patients. The limited increase in glutathione reductase activity during the inflammatory process might lead to an insufficient protective effect at the joint level in rheumatoid arthritis.