The plasma levels of activated thrombin activatable fibrinolysis inhibitor and thrombomodulin in Behçet disease and their association with thrombosis.

OBJECTIVE: To investigate the plasma levels of activated thrombin activatable fibrinolysis inhibitor (aTAFI) and thrombomodulin (TM) in Behçet disease (BD) and their relationship with thrombosis. METHODS: Plasma aTAFI and TM levels were measured by ELISA in 89 patients with BD (18 having venous thrombosis) and in 86 healthy controls. RESULTS: Compared with healthy controls, the BD group had significantly lower levels of aTAFI (13.49+/-8.88 microg/ml vs. 26.76+/-11.57 microg/ml, p<0.0001) and significantly higher levels of TM (3.26+/-1.85 ng/ml vs. 2.6+/-0.69 ng/ml, p=0.0003). Neither aTAFI, nor TM levels differed significantly between BD patients with and without thrombosis (p>0.05). Despite a tendency to positive correlation (r=0.37, p=0.0004) between plasma levels of aTAFI and TM in healthy controls, there was a tendency for negative correlation (r=-0.51, p<0.0001) between these two parameters in BD patients. CONCLUSION: The plasma aTAFI and TM levels do not seem to be related with the presence of thrombosis observed in BD. Increased plasma TM levels in BD may simply reflect endothelial cell activation and dysfunction.

Cyclosporine A-induced neck fibrosis in a patient with adult-onset Still's disease.

Cyclosporine A (CsA) is an immunosuppressive agent used for the prevention of graft rejection during organ and bone marrow transplantation. CsA is also used for the treatment of various inflammatory rheumatic diseases. Although different side effect profiles have been reported, nephrotoxicity, renal vascular damage, hypertension, and gingival hypertrophy are among the most commonly encountered side effects. The development of massive fibrosis in the neck associated with CsA in a 30-year-old male patient with Still's disease is presented herein. Significant regression was observed after the discontinuation of CsA.

Telomerase activity in connective tissue diseases: elevated in rheumatoid arthritis, but markedly decreased in systemic sclerosis.

Telomerase is a reverse transcriptase enzyme contributing to the maintenance of the telomeric structure by adding telomere repeat sequences to chromosomal ends, thus compensating for its shortening. Telomerase activity which is common in cancers and human germ line tissue, may also be increased, although to a lesser extent, in systemic autoimmune diseases. We aimed to evaluate telomerase activity in a group of Turkish patients with various connective tissue diseases. In this cross sectional study, 19 patients with systemic sclerosis (SSc), 15 with systemic lupus erythematosus (SLE), 10 with rheumatoid arthritis (RA) and 14 with primary Sjögren's syndrome (pSjS) were studied. As the control group, 29 healthy subjects were also included. Human telomerase-specific reverse transcriptase (hTERT) was measured in peripheral blood lymphocytes, using online real-time reverse-transcriptase polymerase chain reaction (PCR). We also investigated if hTERT values in each patient group were correlated with clinical parameters and disease activity. Highest hTERT values were observed in RA group (21.24 +/- 28.54), followed by SLE (13.38 +/- 26.05) and pSjS (11.73 +/- 10.59) groups. Only hTERT values in RA group was significantly higher than the healthy control group (7.62 +/- 4.21) (p < 0.05). Interestingly, hTERT values in SSc were very low (2.09 +/- 3.18), even less than the healthy control group. In consistent with previous studies, telomerase activity was increased in SLE and RA. Very low telomerase activity in SSc group was rather surprising. Since existing telomerase data in SSc was limited and telomere shortening was previously reported in SSc, our finding of low telomerase activity in SSc group deserves relevant discussion and further studies.

Hodgkin's lymphoma following treatment with etanercept in ankylosing spondylitis.

It has been well known that anti-TNF drugs might increase lymphoma risk in rheumatoid arthritis (RA), where the rate of lymphoma has already been increased. However, unlike RA, an increased rate of lymphoma has not been reported in ankylosing spondylitis (AS). Hereby, we present a case with AS developing Hodgkin's lymphoma (HL) following 6 months of etanercept treatment. Pathological analysis revealed mixed cellular type of HL. Although we report a single case, it should be kept in mind that anti-TNF drugs might cause lymphoma development not only in RA, but also in AS.

Ankylosing spondylitis-related secondary amyloidosis responded well to etanercept: a report of three patients.

Secondary (AA) amyloidosis is one of the most significant complications of ankylosing spondylitis (AS) that frequently leads to proteinuria and renal dysfunction. Anti-tumor necrosis factor alpha (anti-TNF) agents are promising in inducing clinical remission by suppressing systemic inflammation in AA amyloidosis. We report three cases with AS-related AA amyloidosis that responded well to etanercept therapy. Despite treatment with disease modifying anti-rheumatic drugs, all three patients had active AS, marked proteinuria, impaired renal function, and low serum albumin level. During 1-year treatment with etanercept, all patients experienced gradual improvement in all of these parameters.

Sjögren's syndrome in patients with ankylosing spondylitis.

There are few reports about the coexistence of Sjögren's syndrome (SS) and ankylosing spondylitis (AS). To evaluate the frequency of SS in patients with AS. We studied 70 patients with AS presenting to the university outpatient clinic between January 2002 and November 2003. All the patients were asked about sicca symptoms by using sicca questionnaire. Rheumatoid factor, anti-nuclear antibody, anti-Ro, and anti-La antibodies were examined for each of the patients. Salivary flowmetry for the existence of xerostomia, Schirmer's test, and break-up time for the existence of xerophtalmia were performed in all patients with AS. Minor salivary gland biopsy was performed on the patients with at least three positive responses to the sicca questionnaire and positive xerostomia/xerophtalmia tests. Biopsies were regarded as pathological when they showed focal grade iii and grade IV sialoadenitis according to Chisholm grading criteria. Among 70 AS cases, 56 (80%) were men, 14 (20%) were women, and the mean age was 42 years old. Minor salivary gland biopsy was performed on the 16 patients. Of 16 minor salivary gland biopsies, 7 were assessed as pathological--5 of them showed grade III, and 2 of them showed grade IV sialoadenitis. Of these seven patients, one was anti-Ro-positive, and two were anti-La-positive. There was no patient with normal salivary gland biopsy and anti-Ro and/or anti-La positivity. In our study group, 7 (10%) of 70 AS patients had concomitant SS. Therefore, it seems likely that AS may have pathogenetic association with SS.

Endothelial functions in Behçet's disease.

Behçet's disease (BD) is a systemic vasculitis, capable of involving all types of vessels. Endothelial dysfunction (ED) has been previously documented in BD. The aim of the study was to see whether ED was more prominent in Behçet's patients with vascular involvement (VI) than in those without. The study population consisted of 65 patients with BD, 27 of whom had VI, and 30 healthy controls. High-resolution ultrasound was used to measure endothelium-dependent vasodilatation (EDVD) of brachial artery. Overall, regardless of VI, EDVD was significantly impaired in patients with BD compared with controls (11.4 +/- 6.3 vs 20.4 +/- 9.1%,P = 0.001); however, EDVD was similar in BD patients with and without VI (9.7 +/- 6.3% vs 12.6 +/- 6.1%, P = 0.07). Patients with BD had significantly-higher plasma homocysteine levels than controls (13 +/- 6 micromol/L vs 9 +/- 3 micromol/L, P = 0.001). Plasma homocysteine levels were significantly higher in the subgroup with VI than in those without (15 +/- 7 micromol/L vs 12 +/- 4 micromol/L, P = 0.03); however, we found no positive/significant correlation between plasma homocysteine levels and EDVD. ED is a constant feature of BD, regardless of VI. Etiology of ED in BD is probably multifactorial, including high homocysteine levels. As both ED and elevated homocysteine levels may represent an early atherosclerotic process, a more structured approach to risk factor assessment is needed in BD.

Urinary N-acetyl-beta-D-glucosaminidase (NAG) in lupus nephritis and rheumatoid arthritis.

Increased activity of urinary N-acetyl-beta-D-glucosaminidase (NAG) can be used as an early indicator of damage to the tubular epithelium. Systemic lupus erythematosus (SLE) is a multisystem autoimmune rheumatic disease. Nephritis is known as the most serious complication of SLE and the strongest predictor of poor outcome. In this study urinary NAG excretion was investigated in 24 SLE patients with normal renal function (serum creatinine < or =1.2 mg/dL) and the results were compared with those from 26 untreated patients with rheumatoid arthritis (RA) and 27 healthy controls. The SLE patients were divided into two groups according to their urinary total protein levels: group A consisted of 16 patients with < or =3.5 g/day proteinuria, and group B consisted of eight patients with nephrotic-range proteinuria (>3.5 g/day). Serum and urinary creatinine, total urinary protein levels, and urinary NAG excretion were measured in patients with SLE and RA. In addition, serum C3 and C4 levels were determined in the SLE patients. Renal biopsies were performed in all of the SLE patients. Glomerular lesions were classified according to WHO criteria for lupus nephritis (LN) I-V. The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) was used to assess disease activity. Urinary NAG excretion was significantly higher in the SLE groups than in the healthy controls (P<0.001). In urinary NAG excretion there was also significant difference between SLE groups and RA patients (P<0.001). However, there was no significant difference in NAG excretion between the RA and control groups (P=0.062). Urinary NAG excretion was significantly higher (P<0.05) in group B compared to group A. There were no differences in SLEDAI scores, ages, and serum creatinine levels between study groups (P=0.601, P=0.285, P=0.669, respectively). Elevated SLEDAI values and hypocomplementemia were detected more often in younger patients (P<0.010, r=-0.529 and P<0.010, r=-0.569, respectively). There was a strong positive correlation between proteinuria and urinary NAG activity (P<0.001, r=0.759). These results suggest that the determination of urinary NAG activity may be a useful supplement to the routine biochemical analysis performed on the urine in cases of SLE.

Thrombin activatable fibrinolysis inhibitor in Behçet's disease.

INTRODUCTION: Thrombin activatable fibrinolysis inhibitor (TAFI) is a procarboxypeptidase downregulating plasmin formation, thereby causing a tendency for thrombosis development. Since, Behçet's disease (BD) is a systemic vasculitis, which is commonly complicated by arterial and venous thrombosis, we aimed to find out plasma TAFI levels in BD, compared with healthy controls. We also searched whether plasma TAFI levels were significantly different between Behçet's subgroups with and without thrombosis. MATERIALS AND METHODS: In this study, 105 BD patients (M/F: 64/41; mean age 36+/-1 years), followed up by Ege University Rheumatology Department were enrolled. The exclusion criteria were hemophilia, hyperlipidemia, diabetes mellitus, hepatic diseases renal failure, antiphospholipid positivity, oral contraceptive use and pregnancy. Age-and sex-matched healthy controls (n=53) were also included. Plasma TAFI levels were measured by ELISA. Since TAFI is also an acute-phase reactant, we also measured other inflammatory markers such as C-reactive protein (CRP). RESULTS: Plasma TAFI levels were significantly higher in Behçet's patients (91.1+/-7.4 ng/ml) compared with healthy controls (14.3+/-4.5 ng/ml) (P<0.001), but there were no significant difference between the subgroups with and without thrombosis. In BD, there was no correlation between plasma TAFI levels and CRP. CONCLUSIONS: Regardless of manifest thrombosis, plasma TAFI levels in BD were significantly higher than in healthy controls. High TAFI levels might possibly contribute to the thrombotic tendency in BD. Future studies investigating TAFI gene polymorphism and functional activity are clearly needed, to clarify the exact role of TAFI in Behçet's thrombosis.

Manometric assessment of esophageal motility in patients with primary Sjögren's syndrome.

OBJECTIVE: The aim of this study was to assess the esophageal motility by manometry in patients with primary Sjögren's syndrome. METHODS: Esophageal manometry was carried out in 40 patients with primary Sjögren's syndrome (SS), 15 with rheumatoid arthritis (RA), 15 with RA and secondary SS, and 21 healthy volunteers. RESULTS: We found that the mean lower esophageal sphincter (LES) pressures measured by station pull-through and rapid pull-through techniques were significantly higher in primary SS patients than with healthy controls and RA patients with or without SS (P<0.05). Our study did not show any major differences when comparing the three patient groups (P>0.05). However, peristaltic contraction velocity was lower and peristaltic contraction duration significantly higher at the middle and lower thirds of the esophagus in primary SS patients than in healthy controls (P<0.05). CONCLUSION: The results of our study support the view that various esophageal motility disorders can be found in patients with primary SS which could be related to an increase in LES pressure. We also found no correlation of the esophageal abnormalities with other factors studied, suggesting that the cause of dysphagia is multifactorial in nature.

Platelet-activating factor and P-selectin activities in thrombotic and nonthrombotic Behçet's patients.

OBJECTIVE: The aim of this study was to compare plasma Platelet-activating factor (PAF) and P-selectin (CD62P) activities in Behçet's disease patients with and without thrombosis. METHODS: In this cross-sectional and descriptive study, 30 consecutive Behçet's patients were included, 15 of them with venous thrombosis. All patients were also divided into two subgroups according to the presence or absence of clinical activity. Plasma PAF levels, basal and Ca++ ionophore (A23187)-induced leukocyte (cellular) PAF activities, and platelet-rich plasma DeltaCD62P activity (the mean fluorescent density difference between CD62P phycoerythrin-positive and -negative stains) were evaluated. RESULTS: In the thrombotic group, plasma PAF (P=0.001), basal leukocyte PAF (P=0.017), induced leukocyte PAF (P=0.024), and DeltaCD62P (P=0.023) levels were significantly higher than in the nonthrombotic group. In the whole group of Behçet's patients, there was a positive correlation between plasma PAF and DeltaCD62P levels (r=0.533, P=0.002). When we compared clinically active and inactive patients with respect to the above parameters, there was no significant difference, irrespective of thrombosis. Plasma PAF (P=0.001), basal leukocyte PAF (P=0.004), and DeltaCD62P (P=0.038) levels were significantly higher in the presence of both clinical activity and thrombosis than of clinical activity alone. CONCLUSION: Platelet-activating factor and CD62P may contribute to endothelial injury and thrombosis development in Behçet's disease. These two parameters seem related to the presence of thrombosis rather than clinical activity.

Increased excretions of glycosaminoglycans and heparan sulfate in lupus nephritis and rheumatoid arthritis.

Urinary glycosaminoglycans (GAG) and heparan sulfate (HS) are considered to be markers of early renal involvement. This study was undertaken to demonstrate their excretion patterns in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) with and without arthritis. Serum creatinine and urinary GAG, HS, microalbumin, and creatinine measurements were made in 51 biopsy-proven lupus nephritis (LN) cases, 12 RA patients, and 21 healthy controls. Urinary GAG and HS levels were higher in the LN and RA groups than in controls. Heparan sulfate excretions and SLE disease activity index (SLEDAI) scores were no different between SLE patients with classes 1 and 2 (group A) and those with classes 3, 4, and 5 (group B) renal involvement. However, GAG and microalbumin excretions were significantly high in the latter. There were no differences in GAG and HS excretions between normoalbuminuric, microalbuminuric, and macroproteinuric SLE patients or between those with and without arthritis. In conclusion, urinary GAG and HS, being unrelated to the presence of arthritis, are independent markers of LN. Extrarenal causes or subclinical renal involvement may be responsible in RA due to their increased excretion in these patients.