Cytotoxic T lymphocyte-associated antigen-4 polymorphism in patients with rheumatic heart disease.

Acute rheumatic fever (ARF) is a systemic inflammatory disease occurring as a consequence of an exaggerated immune response to group A, beta haemolytic streptococcal pharyngitis. The molecular mimicry between human target organs/tissues and specific components of the infectious organism leads to the development of autoimmune reactions and cardiac tissue damage in rheumatic heart disease (RHD). Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a negative regulator of T cell activation and proliferation during the immune response. CTLA-4 gene polymorphism has been shown to affect the inhibitory function of CTLA-4. We aimed to analyze the association of CTLA-4 gene locus at position 49 of exon 1 with susceptibility to ARF/RHD. This study included a total of 98 patients with RHD as a sequela of ARF, who fulfilled the revised classification criteria of Jones and 154 healthy unrelated controls. CTLA-4 +49 A/G polymorphism was genotyped by using PCR-RLFP technique. Data was analyzed by binary logistic regression models. The frequencies of GG, GA and AA genotypes were found to be 14%, 47% and 39%, respectively, in patients and 6%, 45% and 49%, respectively, in controls. The GG genotype was found to be significantly different between patients and controls (OR: 3.11; P = 0.016). GA and AA genotypes did not statistically differ between patients and controls. Our data showed a significant association of +49G /G polymorphism in a small patient group with RHD.

Thymidylate synthase genotype and serum concentrations of homocysteine and folate in Behçet's disease.

The aim of this study was to assess whether thymidylate synthase (TYMS) genotype, serum homocysteine, and folate concentrations were related to venous thrombosis in Behçet's disease (BD) patients. The study included 104 BD patients fulfilling the International Study Group Criteria for the diagnosis of BD and 121 healthy individuals-controls. Out of 104 patients, 50 (48%) had vascular involvement: 34 had active-history of venous thrombosis, 16 had arterial involvement (aneurysm), and 11 of these patients had both venous and arterial lesions as confirmed by Doppler ultrasound and/or angiography. Genotype analysis of the TYMS promoter enhancer region was determined by polymerase chain reaction. The distribution of the TYMS genotypes 2R/2R, 2R/3R, 3R/3R, 4R/2R, and 3R/3R were not significantly different between BD patients and control group (p>0.05; 16.5% vs 8.3%, 49.0% vs 53.9%, 31.7% vs 38.0%, 1.9% vs 0%, and 1.0% vs 0%, respectively). TYMS genotypes were not associated with thrombosis and serum homocysteine concentration in BD patients. The mean serum homocysteine level in patients with thrombosis (14.87+/-8.99 micromol/L) was significantly higher than the level in patients without thrombosis (10.78+/-3.81 micromol/L; p<0.05). Serum folate concentrations were not different between the BD patients and the healthy controls. The study results suggest that the distribution TYMS genotype in BD was not different from that of healthy controls. There was no relationship between TYMS genotype and the homocysteine levels in BD patients with thrombosis or without thrombosis.

Genetic susceptibility to rheumatic heart disease and streptococcal pharyngitis: association with HLA-DR alleles.

Acute rheumatic fever (ARF) is a systemic inflammatory disease that develops as a consequence of an exaggerated immune response to group A beta-haemolytic streptococci, which causes pharyngitis. Major manifestations of ARF include carditis, arthritis and chorea. Several investigators have attempted to establish a relation between ARF and human leucocyte antigens (HLA). Heterogeneity in various studies has been found, although associations with certain antigens were reported. The aim of this study was to analyse whether HLA-DR alleles play a role in the resistance or susceptibility to streptococci-related disorders including rheumatic heart disease (RHD) as a sequela of ARF and recurrent streptococcal pharyngitis in Turkish patients. The study included 102 patients with RHD, 71 persons with recurrent streptococcal pharyngitis and 130 healthy controls. HLA-DR alleles were typed by using polymerase chain reaction (PCR)-sequence-specific primers. Positive association with HLA-DRB1*07 allele was found for RHD when compared with healthy controls [29.4% vs 13.1%; P < 0.01, P-corrected: P < 0.01, odds ratio (OR) 2.78, 95% confidence interval (CI) 1.43-5.26] and also for recurrent streptococcal pharyngitis (26.8% vs 13.1%; P < 0.05, P-corrected: P < 0.05, OR 2.44, 95% CI 1.17-3.56). The frequency of HLA-DRB1*11 allele was decreased in patients with RHD (23.5% vs 42.3%; P < 0.01, P-corrected: P < 0.01, OR 0.42, 95% CI 0.24-0.75). Data suggest that HLA-DRB1*07 allele may be a genetic factor in increasing the susceptibility to develop RHD and recurrent streptococcal pharyngitis. HLA-DRB1*11 allele seems to be a protective factor against RHD.

Characteristics of vascular involvement in Behçet's disease.

OBJECTIVE: Behçet's disease (BD) is a multisystemic inflammatory disorder classified among the vasculitides, which can affect all types and sizes of blood vessels. Vascular involvement may be seen in 25-50% of BD patients. In this study, we examined the characteristics of vascular involvement in patients with BD. METHODS: One hundred and eighty patients with BD were included in the study. The diagnosis of vascular involvement was made on clinical signs, by Doppler ultrasonography and/or angiography using computed tomographic or magnetic resonance techniques where appropriate. Detailed clinical characteristics were recorded for each patient. RESULTS: Seventy-one patients (39.4%) had vascular involvement. In patients with vascular lesions, the frequency of male sex was significantly higher than in patients without vascular lesions (89.8% vs. 63.3%, respectively; p < 0.001). Of 71 BD patients with vascular involvement, 68 had venous lesions (95.8%). Three patients had arterial lesions without venous thrombosis. Eleven patients had arterial involvement with venous thrombosis. The most frequent type of vascular involvement was deep venous thrombosis in the lower extremities (n = 56, 78.9%). There was a significant association between deep venous thrombosis and superficial thrombophlebitis (r = 0.325, p < 0.01). Twenty-four patients (33.8%) had vena cava thrombosis and two had vena hepatica thrombosis. In patients with vascular involvement, the frequency of erythema nodosum was significantly higher (p = 0.001) and the frequency of ocular involvement was significantly lower (p < 0.05) than in patients without vascular involvement. CONCLUSION: Our study illustrates the frequency and significance of vascular involvement in BD.

Serum soluble CD30 levels in Behçet's disease.

Behçet's disease is associated with the inflammatory response. Several reports indicate the presence of primarily CD4+ T cells of the Th1 subtype in the inflammation process of the disease. Serum soluble CD30 (sCD30) is reported to be released from CD4+ Th2 type cells and has been suggested to be a marker of Th2 activity. In this study, serum sCD30 levels were measured in active and inactive patients with Behçet's disease, healthy controls and a group of patients with rheumatoid arthritis, typical Th1 disorder using enzyme immunoassay kit. Mean sCD30 value of 54 active patients were found significantly higher than in those of 17 inactive patients (p = 0.027), 20 healthy controls (p = 0.040) and 25 patients with rheumatoid arthritis (p < 0.001). There was a significant correlation between increased sCD30 levels and clinical activity index in active patients with Behçet's disease. High serum levels of sCD30 may reflect the activation of CD4+ T cells or a subset of them in active BD patients. In addition to serum sCD30 levels, measurements of the Th2 cytokines may be a helpful tool for the evaluation of Th2 activity in Behçet's disease.

Behçet's disease presenting as deep venous thrombosis and priapism.

Behçet's disease (BD) is a multi-system inflammatory disorder which may involve the vascular system. Currently, it is general practice to use the International Study Group (ISG) criteria for the diagnosis of BD. However, even though vascular involvement may be seen in one-fourth to one-half of BD patients, and occasionally is the presenting and only manifestation of BD, large vessel disease is not included among the ISG criteria. In this report we describe a patient who had deep venous thrombosis and priapism, but who does not fulfill ISG criteria for the diagnosis of BD.

Evaluation of gastrointestinal involvement of Behçet's disease by nuclear medical techniques.

To evaluate the value of nuclear medicine procedures in the diagnosis of gastrointestinal involvement of Behcet's disease in asymptomatic patients, Tc-99m human immunoglobulin (HIG) and Tc-99m leucocyte (LC) whole body scintigraphies were performed on 30 patients with major symptoms of the disease. Comparison of the results with other diagnostic techniques showed that Tc-99m HIG whole body scanning can be a useful diagnostic aid before the disease becomes clinically active in the gastrointestinal system.

Systemic amyloidosis and sacroiliitis in a patient with systemic lupus erythematosus.

We report a case of a 25-year-old female with juvenile onset systemic lupus erythematosus who developed systemic secondary amyloidosis with renal and gastrointestinal involvement. She has also had radiological signs of bilateral asymptomatic sacroiliitis without lower back pain or HLA-B27 antigen.

Adhesion molecule expression in erythema nodosum-like lesions in Behçet's disease. A histopathological and immunohistochemical study.

Behçet's (BD) is a systemic inflammatory disease with histological evidence for vasculitis. Leucocyte-leucocyte and leucocyte-endothelial cell interactions are critical in inflammatory reactions that are influenced by the expression, activation and shedding of adhesion molecules. We investigated the expression of some adhesion molecules (E- and L-selectin, VLA-4, ICAM-1, PECAM-1, VCAM-1 and CD18 and CD11c chains of beta-2 integrins) on endothelial and inflammatory cells by immunohistochemistry on cryostat sections of erythema nodosum lesions taken from 15 patients with BD and 12 patients with erythema nodosum of unknown cause. Hematoxylin-eosin stained sections of all specimens were also assessed. The major histopathological findings were perivascular mononuclear cell infiltration and secondary vasculitic changes with no difference between the two groups (P > 0.05). However, the frequency of thrombophlebitis was higher in BD (P < 0.001). Endothelial and inflammatory cell adhesion molecule expression did not show any significant difference between groups (P > 0.05). Although VCAM-1 expression and intensity on endothelial cells of BD patients seemed to be lower, this did not reach statistical significance (P = 0.056). We concluded that subcutaneous thrombophlebitis is an important feature of erythema nodosum like lesions in BD, which is almost impossible to understand by physical examination alone. Colchicine, which is known to have some influence on adhesion molecules, might have affected our results, as these showed no significant difference regarding adhesion molecules between the two groups.

The frequency of autoantibodies in Turkish patients with lupus nephritis.

We analysed the frequency of autoantibodies in 44 patients with lupus nephritis. Antinuclear antibody (ANA) was found in 91% of patients by an indirect immunofluorescence technique on HEp-2 cells at the time of study. Anti-dsDNA antibodies were found at high levels in most of the patients using the SynELISA test, which reveals both high and low avidity antibodies, but only in 64% of patients using the DAKO assay, which reveals high avidity antibodies. Anti-histone antibodies were found in 52% of the patients. Anti-SSA/Ro antibodies were positive in 27% of all patients; these patients also had prominent cutaneous involvement and photosensitivity. The frequency of anti-SSB/La and Anti-Sm antibodies was 7%. Immunoblotting experiments confirmed the findings shown by the techniques described above, and anti-ribosomal antibodies were found to be positive in more cases by the latter assay. IgA rheumatoid factor (RF) was more frequent (20.4%) than IgM RF (9.9%). In conclusion, Turkish patients suffering from lupus nephritis seem to express a total autoantibody profile similar to that reported for systemic lupus erythematosus from other parts of Europe.

Lupus vulgaris in a patient with systemic lupus erythematosus and persistent IgG deficiency.

We present the case of a patient with juvenile onset systemic lupus erythematosus (SLE) who developed a persistent, acquired hypogammaglobulinaemia with IgG deficiency. The hypogammaglobulinaemia was probably a complication of high dose corticosteroid treatment. The serum IgG level remained subnormal despite intravenous immunoglobulin therapy. Lupus vulgaris, which developed on the nasal cartilage in this patient with SLE, is not an expected finding. This patient is probably the first reported case of SLE associated with lupus vulgaris.

Seizures and hepatotoxicity following sulphasalazine administration.

Sulphasalazine (SSZ) is a widely used second-line agent for several rheumatic diseases. Most of its side effects are relatively minor and dose dependent. We report a patient with juvenile onset chronic arthritis who developed hepatotoxicity and seizures on the third week of SSZ when the daily dose was increased to 2 g. Clinical and laboratory findings of liver and central nervous system toxicity gradually returned to normal in the month following SSZ withdrawal.

Fibronectin and circulating immune complexes in Behet's disease.

Being a high-molecular-weight adhesive glycoprotein, fibronectin (Fn) is suggested to be a component of immune complexes and may participate in the clearance of immune complexes. In Behçet's disease (BD), a multisystem disorder of unknown etiology, immune complexes have been shown to be deposited in affected tissue during disease activity, suggesting an immune mechanism. This study investigates the relationship between Fn and circulating immune complexes (CIC) and evaluates the changes in the levels of Fn and CIC along with disease activity. In 63 patients (31 active, 32 inactive) with BD, plasma Fn and serum CIC, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and the third and fourth components of the complement system (C3, C4) were studied. The mean ESR, CRP, C3 and C4 levels of active BD patients were found to be significantly higher than those of the inactive BD patient group. Although the mean Fn and CIC levels of BD patients were not significantly different from those of the healthy control group, Fn and CIC values of active BD patients were significantly lower than in the inactive group. Moreover, no significant correlation was observed among Fn levels and ESR, CRP, C3, C4 and CIC levels in BD patients. The result of this study suggest that the variation in Fn concentration is independent of the acute-phase response. The lack of relationship between the CIC and Fn concentrations indicates that IC deposition in the vessel wall is independent of the CIC levels. In order to determine the exact roles of Fn and IC, further studies in tissue specimens are required.

Soluble intercellular adhesion molecule-1 (sICAM-1) in patients with systemic lupus erythematosus.

Circulating sICAM-1 is known to be elevated in various inflammatory disorders. It is further suggested that elevated levels correlate well with disease activity in several autoimmune disorders. The objectives of this study are to determine the serum sICAM-1 levels in patients with systemic lupus erythematosus (SLE) and correlate sICAM-1 levels with clinical and laboratory (ESR, CRP, anti-dsDNA) measures of disease activity. Forty-one patients (34 female, 7 male) all fulfilling 1982 ARA classification criteria for SLE and 16 healthy controls (8 female, 8 male) were included in the study. Disease activity was measured according to SLEDAI. sICAM-1 was determined by ELISA. Mean sICAM-1 in SLE patients (339 +/- 161 ng/ml) were significantly higher than in the controls (216 +/- 85 ng/ml) (p < 0.005). Although slightly elevated in active patients, there was no statistically significant difference between mean sICAM-1 levels of active and inactive SLE patients (349 +/- 183 ng/ml and 316 +/- 103 ng/ml respectively) (p > 0.05). We could not find a correlation between sICAM-1 levels and any organ involvements. Similarly, no significant correlation was found between ESR, CRP, anti-ds-DNA and sICAM-1. These results suggest that although higher than normal, sICAM-1 levels in SLE do not provide additional information over conventional activity markers.

Elevated levels of soluble intercellular adhesion molecule-1 correlate with disease activity in Behçet's disease.

The objective of this study was to measure soluble intercellular adhesion molecule-1 (sICAM-1) in patients with Behçet's disease (BD) and to analyse the relationship of sICAM-1 levels with clinical and some laboratory measures of disease activity. Forty patients with BD fulfilling the International Study Group Criteria for the diagnosis of BD and 20 healthy controls were studied. Twenty patients had active, and 20 patients had inactive disease. Serum sICAM-1 was determined by a sandwich ELISA. The mean (+/- SD) sICAM-1 level was significantly higher in the whole BD group (297.3 +/- 86.6 ng/ml) than in the healthy controls (213 +/- 83.5 ng/ml; P < 0.05). The mean sICAM-1 levels in active and inactive BD patients were 315.7 +/- 76.3 ng/ml and 258.3 +/- 73.3 ng/ml, respectively. The mean sICAM-1 level in active patients was significantly higher than in inactive patients and healthy controls (P < 0.02 and P < 0.001, respectively). No statistically significant difference in mean sICAM-1 levels was found between inactive BD patients and healthy controls (P > 0.05). There was no statistically significant difference between the mean sICAM-1 levels of active patients with (351.3 +/- 77.2 ng/ml) or without vascular lesions (292 +/- 68.8; P > 0.05). In spite of a positive correlation between disease activity and both erythrocyte sedimentation rate and C-reactive protein (CRP; P < 0.01), we found no correlation between sICAM-1 and either of them (P > 0.05). The elevated levels of sICAM-1 may be due to endothelial cell activation and/or damage or may be the result of inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)