Serum levels of GRO-α are elevated in association with disease activity in patients with Behçet's disease

Background Although the etiology of Behçet’s disease (BD) is still unknown, neutrophils are implicated in its pathogenesis. Growth‐related oncogene‐α (GRO‐α) is a potent chemoattractant and activator for neutrophils. Objective To determine the role of GRO‐α in the pathogenesis of BD, we investigated serum GRO‐α levels in patients with BD. Materials and methods Sera from patients with BD (n = 57) and control subjects (n = 26) were measured by enzyme‐linked immunosorbent assay. Serum levels of GRO‐α were compared with clinical symptoms. Results Patients with BD had significantly elevated serum GRO‐α levels compared with healthy controls (121.7 ± 79.2 pg/ml vs. 75.9 ± 20.6 pg/ml, P < 0.01). Concerning the subgroups of BD, serum GRO‐α levels in active patients with BD (n = 35) were significantly higher than in inactive patients with BD (n = 22; 139.0 ± 92.8 pg/ml vs. 94.3 ± 36.2 pg/ml, P < 0.05). Also, as seen in previous studies, serum interleukin‐8 levels in patients with BD (52.4 ± 81.8 pg/ml) were significantly higher than in controls (13.9 ± 19.7 pg/ml, P < 0.01). Enhanced GRO‐α levels correlated with clinical symptoms such as erythema nodosum. Conclusion Our results indicate that serum levels of GRO‐α are elevated in patients with active stage BD, suggesting that GRO‐α may serve as a reliable marker for disease activity of BD.     

Serum and erythrocyte adenosine deaminase activities in patients with Behçet's disease

Objectives Adenosine deaminase (ADA) is a non‐specific marker of the activation of the T cell, which has an important role in the etiology of Behçet's disease (BD). The purpose of this study was to investigate the determination of ADA activity as an index of T‐lymphocyte function in BD, which is known to have an T‐cell‐mediated immune response. Materials and Methods Adenosine deaminase activities in both serum and erythrocytes were measured in 23 untreated patients with BD and in 20 healthy controls. The patients with BD were divided into two groups: active (n = 10) and inactive (n = 13). Results When compared with the control group, serum ADA activity was high (P < 0.01) and erythrocyte ADA activity was significantly low (P < 0.01) in BD. Serum ADA activity of active BD was higher than that of inactive BD (P < 0.01), but erythrocyte ADA activity was found to be lower in active BD than inactive BD (P < 0.01). Comment These findings may provide an additional benefit for the diagnosis of BD and sub‐typing of active and inactive BD.     

Serum leptin concentration is increased in patients with Behçet's syndrome and is correlated with disease activity

Summary Background Behçet's syndrome is a systemic, relapsing immuno‐inflammatory disease with a generalized vasculitis of the microvasculature endothelial dysfunction. Leptin, a recently discovered neuroendocrine hormone, is a metabolic peptide that appears to be involved. Serum proinflammatory cytokines upregulate leptin levels and leptin itself directly induces nitric oxide production from endothelial cells with its specific receptors. Objectives To detect changes of serum leptin concentrations in patients with Behçet's syndrome compared with age‐ and sex‐matched healthy volunteers by using enzyme‐linked immunosorbent assay. We also investigated whether disease activity or the duration of Behçet's syndrome correlates with leptin concentration. Methods Thirty‐five consecutive patients with Behçet's syndrome (41·2 ± 8·4 years, 16 male, 19 female) and 20 age‐ and sex‐matched healthy control subjects (40·4 ± 10·91 years, nine male, 11 female) were included in this study. The body mass index (BMI) [weight (kg) height^?1 (m²)] was calculated for subjects at study enrolment. We measured serum leptin with a leptin enzyme immunoassay kit, and acute‐phase reactants, including erythrocyte sedimentation rate, α₁‐antitrypsin, α₂‐macroglobulin and neutrophil count. The Mann–Whitney U‐test was used for statistical analysis and P < 0·05 was considered significant. Values were expressed as mean ± SD. Results The gender ratio, age and BMI were not substantially different among Behçet's patients and controls. The mean serum leptin concentrations in patients with Behçet's syndrome (16·8 ± 7·49 ng mL^?1) were significantly (P < 0·001) higher than in healthy control volunteers (7·5 ± 2·77 ng mL^?1). Active Behçet's patients had significantly (P = 0·001) higher leptin concentrations (20·5 ± 7·99 ng mL^?1) when compared with patients in inactive periods (12·8 ± 4·43 ng mL^?1). In addition, patients with longer disease duration (mean, 20·1 ± 5·15 years) had also significantly (P = 0·013) higher leptin concentrations (20·2 ± 8·52 ng mL^?1) than those with shorter disease duration (13·4 ± 4·52 ng mL^?1) (mean, 7·4 ± 3·29 years). All acute‐phase reaction parameters were found to be significantly (for each, P < 0·01) increased in active disease. Conclusions Leptinmay have a role in modulating endothelial function and may be involved in mechanisms for vessel endothelium repair, during an exacerbation as well as in chronic disease.     

Increased plasma adrenomedullin levels in patients with Behçet's disease

BACKGROUND: Beh?et's disease (BD) is a chronic systemic inflammatory disorder affecting multiple organs with a generalized vasculitis of arteries and veins. Endothelial dysfunction is one of the prominent features of BD. Adrenomedullin (AM) is a peptide produced not only in normal adrenal medulla but also in the vascular smooth muscle cells and endothelial cells, and its role in the course of BD has not been previously described. OBJECTIVE: To detect changes of plasma AM concentrations in patients with BD compared with age- and sex-matched healthy subjects by using high-performance liquid chromatography (HPCL). We also investigated if disease activity or the duration of BD correlates with AM levels. METHODS: Forty-two consecutive patients with BD (38.5 +/- 11.1 years, 19 male and 23 female) and 20 healthy age- and sex-matched control subjects (39.5 +/- 10.9 years, 8 male and 12 female) were included in this study. We measured plasma AM levels by HPCL, and acute-phase reactants including alpha(1)-antitrypsin and alpha(2)-macroglobulin, neutrophil count and the erythrocyte sedimentation rate. RESULTS: Mean +/- SD plasma AM levels in patients with BD (73.22 +/- 25.55 pmol/l) were significantly higher (p < 0.001) than in healthy control volunteers (21.35 +/- 12.37 pmol/l). Patients with active BD had similar plasma AM concentrations (79.32 +/- 21.89 pmol/l) with patients with inactive disease (67.44 +/- 29.92 pmol/l). On the other hand, patients with longer duration of the disease (mean duration, 13.9 +/- 3.8 years) had significantly higher plasma AM levels (83.99 +/- 19.71 pmol/l; p = 0.005) than patients (62.45 +/- 26.57 pmol/l) with shorter duration of the disease (mean duration, 5. 5 +/- 2.3 years). All acute-phase reaction parameters were found to be significantly increased in the active disease. CONCLUSION: Considering its endothelial cell implications, AM may be involved in reparatory vessel endothelium mechanisms, especially in the chronic disease.     

Serum lipoprotein (a) levels and Behçet's disease: is there an association?

Background Behçet's disease (BD) is a multisystemic inflammatory disorder found in individuals with a particular genetic background. Hemostatic studies in BD support an imbalance towards a prothrombotic state at different levels. Lipoprotein (a) (Lp(a)) has atherogenic and thrombogenic properties. It is mostly under genetic regulation. We investigated the possible relationship between Lp(a) and BD. Methods Forty patients diagnosed with BD and 40 healthy controls were enrolled. The clinical characteristics of the patients were recorded. Serum total cholesterol, high-density lipoprotein (HDL), very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), apolipoprotein A1, apolipoprotein B, and Lp(a) levels of the two groups were assessed and compared statistically. Results All patients (100%) had oral aphthous ulcers. Thirty (75%) had genital ulceration, 37 (92.5%) had either erythema nodosum or papulopustular lesions, and 10 (25%) had eye involvement. Twelve (30%) had a positive pathergy test. Four (10%) had vascular involvement. The Lp(a) level of the patient population was 19.6 ± 18.8 mg/dL. This level was higher than that of the controls, but not statistically significant. The Lp(a) levels of the four patients with vascular complications were within normal limits. Conclusions Lp(a) is of interest, as it is a genetically determined parameter that was found to be high in BD patients in our study group. The levels were independent of thrombotic complications, perhaps suggesting a different role for this lipoprotein in the etiopathogenesis of BD. Further studies with a larger number of patients are essential to discover the exact role of Lp(a) in BD.     

Vascular endothelial growth factor levels are increased and associated with disease activity in patients with Behçet's syndrome

Background/aims Vascular endothelial growth factor (VEGF) is a cytokine participating in inflammation with potent endothelial cell effects. It is produced by macrophages, neutrophils and vascular endothelial cells and can alter vessel permeability. Behçet's syndrome is a systemic inflammatory disorder with unknown etiology. Vascular endothelial dysfunction is one of the prominent features of the disease. We previously demonstrated the possible involvement of proinflammatory cytokines [tumor necrosis factor (TNF)‐α, soluble interleukin‐2 receptor (sIL‐2R), interleukin (IL)‐6 and IL‐8], nitric oxide (NO) and adrenomedullin in the etiopathogenesis of Behçet's syndrome. Since VEGF expression is induced by these cytokines and VEGF itself is a potent stimulator of NO production with endothelial cell effects, this study aimed to investigate whether VEGF was affected during the course of Behçet's syndrome. We also assessed the possible involvement of VEGF in ocular Behçet's syndrome or in disease activity. Methods This multicenter case–control study included a total of 39 patients with active (n = 22) or inactive (n = 17) Behçet's syndrome (mean age, 38.1 ± 10.4 years; 21 men and 18 women) satisfying International Study Group criteria, and 15 healthy hospital‐based control volunteers (mean age, 39.2 ± 9.3 years; eight men and seven women) matched for age and gender from a similar ethnic background. Patients were examined by a dermatologist and an ophthalmologist with an interest in Behçet's syndrome. Plasma VEGF concentrations were measured using a newly established enzyme‐linked immunosorbent assay. Clinical findings and acute‐phase reactant parameters such as erythrocyte sedimentation rate, α₁‐antitrypsin, α₂‐macroglobulin, and neutrophil count were used to classify the disease in Behçet's patients as active or inactive. The Wilcoxon test or the Mann–Whitney U‐test was used for statistical analysis as indicated and the results were expressed as mean ± SD, with range. Results The mean plasma VEGF level in patients with Behçet's syndrome (291.9 ± 97.1 pg/mL; range 121–532 pg/mL) was higher than that in control subjects (103.0 ± 43.6 pg/mL; range 25–187 pg/mL) and the difference was significant (P < 0.001). Patients with active disease had significantly (P < 0.001) higher VEGF levels than patients with inactive disease (347.6 ± 87.1 vs. 219.9 ± 51.6 pg/mL). In addition, ocular Behçet's patients (n = 23) had higher VEGF levels (315.7 ± 92.1 pg/mL) than nonocular patients (n = 16, 257.8 ± 96.6 pg/mL) and the difference was of borderline significance (P = 0.041). The levels of all acute‐phase reactant parameters were significantly higher in the active stage than in the inactive stage (for each, P < 0.01) or in control subjects (for each, P < 0.001). Conclusions VEGF may participate in the course of Behçet's syndrome, especially in the active stage, and elevated levels of VEGF may be an additional risk factor for the development of ocular disease, contributing to poor visual outcome.     

Serum interleukin-8 as a serologic marker of activity in Behçet's disease

Background Immune dysregulation has been shown to be one of the major aspects of the yet unknown pathogenesis of Behçet's disease. Interleukin-8 (IL-8), a major chemokine with pivotal effects concerning leukocytes and endothelial cells, has been found to be elevated in patients with Behçet's disease. Aim To evaluate the significance of elevated levels of IL-8 with respect to the activity of Behçet's disease. Methods Sixty-seven consecutive patients with Behçet's disease (37 males, 30 females; 32.5 ± 9.3 years) were enrolled in our study. The number of active clinical manifestations at the time of serum sampling was recorded. The degree of association between disease activity and IL-8, C-reactive protein, and erythrocyte sedimentation rate was assessed. Results Serum levels of IL-8 increased as the number of clinically involved organs increased (P < 0.05). C-reactive protein and the erythrocyte sedimentation rate showed no correlation with disease activity. Conclusions Our study confirms that the IL-8 level is a more sensitive marker of disease activity than the erythrocyte sedimentation rate and C-reactive protein. It may be assumed that IL-8 plays an important role in the pathophysiology of Behçet's disease.     

Complex aphthosis and Behçet's disease

Complex aphthosis is a disorder in which patients develop recurrent oral and genital aphthous ulcers or almost constant, multiple oral aphthae, without manifestations of systemic disease. Beh?et's disease is a multisystem disease characterized clinically by oral and genital aphthae, arthritis, cutaneous lesions, and ocular, gastrointestinal, and neurologic manifestations. This article reviews both disorders, including their clinical and histologic presentations, factors in pathogenesis, and includes an overview of therapeutic modalities.     

Acetylator phenotype in Behçet's disease

The purpose of this study was to determine the acetylator status in Behçet's disease (BD) patients and compare it to a matched group of normal individuals. Thirty‐seven healthy volunteers and forty‐one BD patients were included. Detailed history was taken from the patients. HLA‐B51 was determined in the BD patients. In addition, the Clinical Manifestation Index (C.M.I.) was determined for each patient. Pathergy test was also done. After an overnight fast, each control subject and patient received a single oral dose of 100 mg of DDS. A blood sample was collected after 3 hours and the plasma was separated for determination of dapsone/monoacetyldapsone by HPLC. The frequency of slow acetylators in healthy individuals was 70.2%, while the frequency of rapid acetylators was 29.8%. The frequency of slow acetylators in BD patients was 53.7%, while the frequency of non‐acetylators (undetected monoacetyldapsone MADDS in plasma) was 46.3%. There were no rapid acetylators among the BD patients. There was a strong negative association between the acetylator status and the severity of BD. In addition, acetylator status correlated with HLA‐B51, in that BD patients with positive HLA‐B51 were characterized by a very slow or non‐acetylator status. Slow or non‐acetylators had more severe BD. We conclude that BD patients have a unique acetylator status. This finding may have implications for the theories for the pathogenesis of the disease as well as for therapeutic aspects.     

Helicobacter pylori and Behçet's disease

BACKGROUND: Recent investigation of the etiology of Beh?et's disease (BD) has focused on heat shock proteins (HSP) which belong to the HSP 60 family. Both the gastric pathogen Helicobacter pylori (HP) and BD may cause ulcers in the gastrointestinal tract and, HP expresses HSP 60. OBJECTIVE: Whether HP is linked to the pathogenesis of BD or not, and to investigate the influence of HP eradication on clinical parameters of BD. METHODS: Patients with BD were divided into two groups. Group I comprised 49 patients and was investigated for HP seroprevalence and compared with age- and sex-matched controls. Group II comprised 20 patients with BD and HP infection diagnosed by serological and endoscopic examinations as well as the rapid urease test (RUT). A 1-week eradication therapy was administered for HP infection. Patients were examined for the course of BD at monthly intervals. Two months after the eradication therapy, patients underwent an endoscopic examination and RUT for eradication control. Seven patients were excluded because of eradication failure. Thirteen patients were evaluated for the influence of HP eradication on clinical manifestations of BD. The number and size of oral and genital ulcers before the eradication and at the end of the follow-up period were compared statistically. RESULTS: HP seroprevalence between patients with BD and controls did not show significant difference. In 13 patients with BD, the number and size of oral and genital ulcers diminished significantly and various clinical manifestations regressed after the eradication of HP. CONCLUSION: HP may be involved in the pathogenesis of BD.     

Cardiac complications in Behçet's disease

Summary Behçet's disease (BD) is a multisystem disease of unknown aetiology characterized by chronic relapsing oro‐genital ulcers, uveitis, and systemic involvement including articular, gastrointestinal, cardiopulmonary, neurologic and vascular pathology. Vascular involvement is observed in 30% of cases. Although the pathogenic mechanisms underlying the thrombotic disposition in BD are not well known, prothrombin (PT) gene mutations may be one factor that contributes to the development of vascular involvement in this disorder. We report a case of BD with a PT gene mutation, presenting with cardiovascular involvement.