Serum hyaluronic acid in patients with veno-occlusive disease following bone marrow transplantation

The development of hepatic veno-occlusive disease following bone marrow transplantation is associated with high-dose combination cytoreductive therapy. Experimental models have suggested that drug-induced injury to hepatic sinusoidal endothelial cells is involved in the pathogenesis of this syndrome. Hyaluronic acid is a polysaccharide that is metabolized, almost exclusively, by hepatic sinusoidal endothelial cells. The aim of the present study was to evaluate serum hyaluronic acid as a marker for endothelial cell injury in patients with veno-occlusive disease following bone marrow transplantation. Hyaluronic acid was measured in sera from patients with and without veno-occlusive disease using an enzyme-linked protein binding assay. Mean peak serum hyaluronic acid levels were significantly greater in patients who had a diagnosis of VOD compared to those transplant patients who did not, 1173.4 +/- 982.9 vs 444.9 +/- 735.6 ng/ml (P = 0.01). Serial serum samples obtained from a separate cohort of patients also demonstrated that serum hyaluronic acid levels were higher in patients with moderate or severe veno-occlusive disease compared to those with none or mild disease at days 7, 17 and 25 following transplantation (greatest difference at day 25: 366 +/- 327 vs 126 +/- 151, P = 0.01). Serum hyaluronic acid levels are increased in veno-occlusive disease and increase over time in patients with severe disease. Further studies are required to determine if elevated serum hyaluronic acid levels are due to decreased clearance by injured hepatic sinusoidal endothelial cells or increased production from early hepatic fibrogenesis associated with the acute liver injury.     

Circulating hyaluronic acid levels vary with physical activity in healthy subjects and in rheumatoid arthritis patients. Relationship to synovitis mass and morning stiffness

We evaluated the possible influence of physical activity on serum levels of hyaluronic acid (HA), plasma levels of elastase, and serum levels of procollagen III peptide. In 15 healthy individuals, HA increased from 26 +/- 9 micrograms/liter (mean +/- SD) before arising from a night's sleep to 54 +/- 24 micrograms/liter 1 hour after arising and performance of normal morning activities (P less than 0.001). HA in 14 patients who had inflammatory arthritis increased from 124 +/- 104 micrograms/liter to 402 +/- 232 micrograms/liter under the same conditions (P less than 0.001). The elevation due to physical activity was significantly (P less than 0.001) higher in patients with rheumatoid arthritis (RA) than that found in controls. A slight increase of HA in the afternoon was also observed in healthy subjects who performed heavy exercise, but a marked increase was seen in RA patients who performed moderate exercise. In another group of 24 RA patients, a more standardized blood sampling was performed before arising and during normal morning activities. An increase in HA was significantly (P less than 0.001) correlated to the synovitis mass, estimated by the Ritchie articular index. Maximum increases of HA were seen 30 and 60 minutes after arising; thereafter, levels decreased to those measured at rest. During the morning activities, procollagen III peptide remained stable, while plasma elastase tended to increase. It is proposed that HA, produced in the joint tissue structures and accumulated at rest, is carried by the lymph vessels to the general circulation during physical activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship between serum hyaluronic acid level and disease activity in early rheumatoid arthritis

OBJECTIVES: To measure hyaluronic acid (HA) levels, which are raised in active rheumatoid arthritis (RA), in patients with early RA, and to assess the correlation with clinical and laboratory indices of disease activity and with subsequent radiographic erosive status. PATIENTS AND METHODS: Patients fulfilling ACR criteria were recruited into a prospective cohort within 6 months of disease onset and reviewed every 6 months. An HA binding protein based sandwich ELISA was used to measure HA in 240 sera from 82 patients at regular intervals. RESULTS: Patients had higher HA levels than age matched healthy blood donor controls (median 37.4 v 29.1 ng/ml, respectively, p<0.02), which increased with more prolonged disease. Baseline HA level correlated with measures of disease activity, including swollen and tender joint counts, HAQ, global assessments, ESR, and CRP; was higher in men; and increased with age. There was no relationship with HLA-DRB1 shared epitope or rheumatoid factor status. At 6 and 12 month follow up visits, HA levels were higher in patients who later developed erosions. However, a raised HA level was not a good predictor of erosions. CONCLUSIONS: Serum HA level correlates with clinical and laboratory measures of disease activity in early RA, but is unlikely to be of practical use in clinical practice.     

Serum hyaluronic acid levels in patients with ankylosing spondylitis

Our aim in this study was to investigate serum hyaluronic acid (HA) levels and the relationship between clinical parameters in ankylosing spondylitis (AS). Approximately 30 patients with AS and 30 healthy individuals were recruited in this study consecutively. Cross-sectional study was planned, and demographic, clinical, functional, radiological, and laboratory data of patients were evaluated. Disease activity, functional status, and quality of life were assessed, respectively, with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Short-Form 36 (SF-36). Mander Enthesis Index (MEI) was used for evaluation of enthesis involvement. We examined serum concentrations of HA (ng/ml) in patients with AS and controls. The mean ages of patients and control group were 38.3 (SD=10.8) and 42.7 (SD=10.6) years, respectively. The mean of serum HA levels in AS patients was 40.4 (SD=34.8) ng/ml and in controls was 24.9 (SD=20.2). There was significant difference of HA levels between two groups (p=0.04). Furthermore, there was a significant correlation between HA level and distance of hand-floor (r=0.444, p=0.014), modified lumbar Schober's (r= -0.413, p=0.023), distance of chin to chest (r=0.436, p=0.016), right sacroiliit grade (r=0.601, p<0.001), left sacroiliit grade (r=0.610, p<0.001), C reactive protein level (r=0.404, p=0.027), albumin (r= -0.464, p=0.010), C3 (p=0.449, p=0.013), and IgA levels (r=0.369, p=0.045). However, there was no significant correlation between HA levels with MEI, BASFI, BASDAI, and SF-36 (p >or= 0.05). Serum HA level was significantly higher in AS patients than controls. However, there was no significant correlation between serum HA level and disease-specific measures as BASFI and BASDAI; it had significant relation with spinal mobility limitation, sacroiliitis, and laboratory parameters related with acute inflammation. The serum HA level may be a potential biomarker of axial inflammation and disease severity in AS.     

Serum and synovial fluid levels of interleukin-17 in correlation with disease activity in patients with RA

The aim of this study was to evaluate serum and synovial levels of IL-17A by ELISA in rheumatoid arthritis (RA) and find out the correlations between IL-17A levels and various clinical, laboratory parameters and RA disease activity and severity indices. Group I consists of 30 adult active RA patients fulfilling the ARA 1987 revised criteria, with knee effusion and receiving basic therapy, and with a mean age of 41.47 ± 11.49 years and mean disease duration of 9.5 ± 4.16 years. Group II consisted of 13 healthy volunteers, age- and sex-matched, with a mean age of 39.08 ± 14.19 years. RA patients showed significantly higher mean serum IL-17A levels than controls (11.25 ± 9.67 vs. 0.6 ± 1.4 pg/mL, respectively, p = 0.0002). Synovial IL-17A levels showed a significant positive correlation with serum IL-17A levels (r = 0.5 and p = 0.005). RA patients with negative rheumatoid factor (RF) had non-significantly higher mean serum IL-17A levels (12 ± 9.86 pg/mL) compared to those with positive RF (10.82 ± 9.81 pg/mL); however, the mean synovial IL-17A levels were nearly the same. Significant positive correlations were found between both serum and synovial IL-17A levels and DAS-28 scores (r = 0.556, 0.392 and p = 0.001, 0.032, respectively). RA patients with class III functional status showed significantly higher mean serum IL-17A levels (17.53 ± 13.43 pg/mL) than classes I and II (8.97 ± 6.97 pg/mL, p = 0.009). These led us to conclude that the elevated serum and synovial IL-17A levels in RA patients parallel the degree of disease activity and severity. This may highlight the usefulness of IL-17 (especially serum level) as a possible marker for more aggressive joint involvement and damage.     

Cumulative disease activity predicts incidental hearing impairment in patients with rheumatoid arthritis (RA)

We previously reported that 24 % of 113 rheumatoid arthritis (RA) patients had hearing impairment (HI). We investigated if disease activity was a predictor of incidental HI. One hundred and four patients completed three consecutive 6 months-apart rheumatic evaluations and concomitant audiometric evaluations which included at least an interview, an otoscopic evaluation, and a pure tone audiometry. HI was defined if the average thresholds for at least one of low-, mid-, or high-frequency ranges were ≥25 decibels (dB) hearing level in one or both ears. Appropriated statistics was used. Internal review board approval was obtained. Patients were most frequently middle-aged (43.4?±?13.3 years), female (89.4 %), and had median disease duration of 5 years and low disease activity. All were receiving RA treatment. At inclusion, 24 patients had HI which was sensorineural in 91.7% of them. Among the 80 patients without HI at baseline, 10 (12.5 %) developed incidental HI, and they had more disease activity either at baseline ([median, range] disease activity score-28 joints evaluated-C-reactive protein [DAS28-CRP], 3.9 [1.6–7.3] vs. 2.1 [1–8.7], p?=?0.006) or cumulative previous incidental HI (3.4 [1.8–4.8] vs. 2 [1–6.2], p?=?0.007) and were more frequently on combined methotrexate and sulfasalazine (20 vs. 1.4 %, p?=?0.05) than their counterparts. In the adjusted Cox proportional model, cumulative DAS28-CRP was the only variable to predict incidental HI (odds ratio, 1.8; 95 % confidence interval, 1.1–2.7; p?=?0.01). Almost 13 % of RA patients with short disease duration and low disease activity developed incidental HI during 1 year. Cumulative disease activity predicted incidental HI.     

Serum YKL-40 concentrations in patients with rheumatoid arthritis: relation to disease activity.

OBJECTIVE: YKL-40, also called human cartilage glycoprotein-39, is secreted by chondrocytes, synovial cells, macrophages and neutrophils. Studies have shown that YKL-40 is an autoantigen in rheumatoid arthritis (RA). We evaluated whether serum YKL-40 was related to disease activity in patients with RA. METHODS: Serum YKL-40 was determined by radioimmunoassay in 156 patients with RA during a 1 yr longitudinal study. RESULTS: Serum YKL-40 was increased in 54% of the patients with clinically active disease. Patients with clinically active disease initially who became inactive after 12 months had a significant decrease in serum YKL-40 (-30%, P < 0.002) and patients who changed from inactive to active disease had an increase in serum YKL-40. Patients who remained active had unchanged serum YKL-40 during the study. Serum YKL-40 decreased rapidly (-24% after 7 days, P < 0.01) during prednisolone therapy, and more slowly in patients treated with methotrexate only (-15% after 60 days, P < 0.01). Patients with early RA (disease duration < 3 yr, n = 50) and a persistently elevated serum YKL-40 were at risk of radiological disease progression as determined by Larsen score. CONCLUSION: Serum YKL-40 varies according to disease activity in RA, but provides in some respect information different from conventional markers. Our previous studies are consistent with a local release of YKL-40 in the arthritic joint followed by a secondary increase in serum YKL-40. YKL-40 may prove to be a new tool for the study of disease activity and pathophysiology of RA.     

Serum pentraxin 3 levels in rheumatoid arthritis patients and its association with disease activity

Aim of the workThis work aimed to evaluate serum pentraxin 3 (PTX3) levels in rheumatoid arthritis (RA) patients and to study the association with the disease activity.Patients and methodsSixty RA patients and 26 matched controls were included. In patients, clinical examination was performed and disease activity score (DAS28) assessed. Serum PTX3, rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were measured.ResultsThe mean age of the patients was 54.9 ± 11.7 years, and the median (Min–Max) of disease duration was 24 (3.96–60) months and 91.7% were females. The mean DAS28 was 4.16 ± 1.77, the ESR was 38.6 ± 23.03 mm/1st h, CRP was 14.9 ± 8.6 mg/l, RF was 49.6 ± 28.1 IU/ml and the median anti-CCP was 375. Serum PTX3 level was significantly higher in RA patients (2.82 ± 0.48 pg/ml) compared to controls (2.56 ± 0.29 pg/ml) (p = 0.003). There was a significant difference in serum PTX3 level according to the disease activity: remission (2.49 ± 0.16 pg/ml), low (2.61 ± 0.33 pg/ml), moderate (2.90 ± 0.53 pg/ml) and high (3.01 ± 0.51 pg/ml) (p = 0.016). There was a significant correlation between serum PTX3 level with disease activity (r = 0.39, p = 0.002) and CRP (r = 0.49, p < 0.001). There was no significant correlation between serum PTX3 level and the RF (r = 0.25, p = 0.054), anti-CCP (r = 0.18, p = 0.17) and ESR (r = 0.09, p = 0.51). PTX3 and CRP showed a good sensitivity and specificity in predicting RA disease (p = 0.006 and p < 0.001, respectively).ConclusionPTX3 can be considered as a marker of a positive acute phase response and may serve as a potential novel biomarker for detecting RA activity.     

Serum amyloid-A protein concentration in rheumatoid arthritis and its role in monitoring disease activity.

The serum concentrations of serum amyloid-A protein (SAA), C-reactive protein (CRP), and alpha 1-acid glycoprotein (alpha 1-AGP) have been measured in 185 patients with rheumatoid arthritis. SAA and CRP concentrations correlated well (r = 0.86) both within and above the normal ranges, though SAA showed a greater incremental increase than CRP. All patients with normal SAA levels also had normal CRP and alpha 1-AGP concentrations. In contrast, in 40% of patients with normal CRP and alpha 1-AGP concentrations the SAA was raised, sometimes markedly so. The clinical and serological assessments of disease activity in these patients were not significantly different from those with concomitantly raised levels of CRP. These findings suggest that SAA is a more sensitive marker of inflammation than is CRP. The role of the measurement of SAA as a monitor for inflammatory disease activity is discussed.     

Serum procalcitonin concentration in patients with Kawasaki disease

BACKGROUND: Procalcitonin (PCT) is a new parameter of inflammation, the clinical usefulness of which is currently being evaluated. MATERIALS AND METHODS: We determined simultaneously the serum concentrations of PCT and C-reactive protein (CRP) as well as the white blood cell (WBC) count in 25 patients with Kawasaki disease (KD), 17 with bacterial infections, 10 with systemic autoimmune diseases, 17 with viral infections and 18 healthy children. The optimal cut-off value of each parameter for predicting coronary aneurysms was determined using receiver operating characteristic curves. RESULTS: Significantly higher serum concentrations of PCT were observed in patients with KD (2.3 +/- 3.0 ng/ml) and bacterial infections (2.2 +/- 2.9 ng/ml) than in patients with autoimmune diseases (0.4 +/- 0.4 ng/ml) or viral infections (0.4 +/- 0.3 ng/ml), or in healthy children (0.2 +/- 0.1 ng/ml). The serum PCT but not the WBC count or CRP, differentiated the KD patients from the patients with autoimmune diseases. The optimal cut-off value of 3.0 ng/ml of PCT increased the prediction rate of coronary aneurysms that subsequently occurred in 4 (16%) patients with KD. CONCLUSIONS: The serum PCT may be clinically useful for determining the severity of KD and for narrowing the differential diagnosis of patients with inflammatory diseases.     

Serum interleukin-23 level in rheumatoid arthritis patients: Relation to disease activity and severity

Aim of the work

The aim of this study was to evaluate interleukin-23 (IL-23) level in the sera of rheumatoid arthritis (RA) patients and to determine its relation with disease activity and severity.

Serum selenium concentration in patients with Wilson's disease

BACKGROUND/AIMS: Wilson's disease is a genetically determined disorder of copper metabolism in the liver. Due to the toxic accumulation of this trace element, body organs are damaged by free radical generation, lipid peroxidase and inhibition of synthesis of some proteins. Behavior of anti-oxidative factors in Wilson's disease has not been completely evaluated yet. The aim of the study was to assess blood serum concentrations of selenium in patients with Wilson's disease. METHODOLOGY: Twenty-five patients with Wilson's disease and 30 healthy volunteers, constituting a control group were included in the study. The patients were in good clinical condition. In all the subjects blood serum concentrations of selenium were tested using the atomic absorption spectroscopy, hydride generation method. RESULTS: Selenium concentrations in the blood serum of the patients and healthy controls did not show statistical differences between both groups. Correlations between selenium concentrations and biochemical parameters: activity of alanine and aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltranspeptidase, concentration of bilirubin, albumin and gamma globulin, international normalized prothrombin index as well as serum copper, ceruloplasmine and 24-h urine copper excretion were assessed. Statistically significant correlation was found only between selenium concentration and aspartate aminotransferase activity. No statistically significant differences between selenium concentrations in the serum of patients with different forms of Wilson's disease were found. CONCLUSIONS: On the basis of the results obtained in the study it can be assumed that in treated patients with Wilson's disease the antioxidant status measured as serum selenium concentration is comparable to healthy controls.     

Serum alpha 1 antichymotrypsin concentration as a marker of disease activity in rheumatoid arthritis.

Serum alpha 1 antichymotrypsin (alpha 1ACT), C reactive protein (CRP), orosomucoid, and erythrocyte sedimentation rate (ESR) were measured sequentially in 20 patients with rheumatoid arthritis (RA) treated with gold or penicillamine. Pain score, morning stiffness, grip strength, and articular index were measured and a Mallya score calculated. Based on a total of 148 sets of observations, significant correlations were found between alpha 1ACT and other variables (p less than 0.001 except morning stiffness at p less than 0.05). The actual correlation coefficients indicated a closer association with the other laboratory tests, CRP (0.62), orosomucoid (0.69), and ESR (0.61), than with clinical measurements: pain score (0.38), articular index (0.41), grip strength (-0.3), morning stiffness (0.19), and Mallya score (0.5). Sequential data on individual patients showed differing patterns of change in the variables indicating the importance of measuring more than one acute phase protein (APP), especially when CRP is inappropriately low. Serum alpha 1ACT concentration does reflect disease activity in RA. Its potential advantages are discussed.     

Calprotectin in patients with rheumatoid arthritis: relation to clinical and laboratory variables of disease activity.

Calprotectin (L1) is a major granulocyte and monocyte protein which is released during activation of these cells. The plasma level of L1 is thought to reflect disease activity in rheumatoid arthritis (RA). In our cross sectional study of 70 patients with RA, L1 had significant correlations with erythrocyte sedimentation rate (r = 0.50), C-reactive protein (r = 0.58), orosomucoid (r = 0.62), platelet count (r = 0.42), leukocyte count (r = 0.33) and IgM rheumatoid factor (r = 0.32); and with the following clinical variables: number of swollen joints (r = 0.24), grip strength (r = -0.22), PIP joint circumferences (r = 0.33) and a combined global assessment score (r = 0.24). L1 was higher in seropositive (median 14,861 micrograms/l) than seronegative patients (median 10,487 micrograms/l) (p less than 0.03).