The role of vitamin D receptor gene polymorphisms in the pathogenesis of Behçet's disease: A case-control study in Turkish population.

BACKGROUND: Behçet's disease (BD) is an inflammatory disorder characterized by oral aphthous lesions, uveitis, and genital ulcerations. The vitamin D receptor (VDR) has a crucial role in the pathogenesis of this disease because it mediates the functions of vitamin D in the immune system. Alterations of VDR expression related to polymorphic alleles of the VDR gene may play a pathogenic role in BD and BD's clinical presentations. METHODS: 150 BD patients and 150 healthy controls were included and genotyping was carried out by polymerase chain reaction/restriction fragment length polymorphism. RESULTS: Significant differences between patients and controls in rs1544410, rs2228570, and rs731236 genotypes were observed (respectively, p = 0.04, p = 0.007, p = 0.012). The clinical characteristics of BD patients were evaluated and patients with ocular lesions had a higher percentage of rs1544410 A alleles (p = 0.004), and patients with oral aphthous lesions, a positive pathergy tests, and arthritis had more rs2228570 C alleles than patients without these clinical findings (respectively, p < 0.001, p = 0.021, p = 0.045). CONCLUSION: VDR gene polymorphisms may possibly have a role in the pathogenesis of BD through their effects on VDR expression and may be associated with the increased risk of several clinical findings.

Serum interleukin-37 level and interleukin-37 gene polymorphism in patients with Behçet disease.

Behçet's disease (BD) is a chronic inflammatory disease. The etiopathogenesis of BD is not well understood and several cytokines and genetic factors have been investigated. Interleukin (IL)-37, which a member of IL-1 family is an anti-inflammatory cytokine. The aim of the study was to analyze serum IL-37 level and IL-37 gene polymorphisms to assess its possible role in BD. Two hundred twenty-three patients with BD and 80 healthy controls (HC) were enrolled. Serum IL-37 level was measured using an enzyme-linked immunosorbent assay (ELISA). Deoksiribo Nucleic acids (DNA) were extracted using a genomic DNA isolation kit. Single nucleotide polymorphism (SNP) of IL-37 gene (rs3811047) was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP) methods. Serum IL-37 level was not significantly different in BD and HC (p > 0.05). Serum IL-37 level was not associated with the disease activity (p > 0.05). However, its level was higher in mucocutaneous involvement compared with systemic involvement (p = 0.002) and HC (p = 0.005). IL-37 gene polymorphisms were similar in BD and HC (p > 0.05). IL-37 may play a role in the etiopathogenesis of BD by contributing to manifestation with more moderate clinical symptoms.

Investigating the role of IL-33 in the pathogenesis of Behçet's Disease.

OBJECTIVES: Behçet's disease (BD) is an inflammatory disease, characterized by oral aphthous lesions, recurrent uveitis, skin lesions, and genital ulcerations. Increased release of several cytokines may play a role in the inflammatory stages of BD. IL-33, a member of the IL-1 cytokine superfamily, plays an important role in inflammation. We analyzed serum IL-33 concentration in BD patients to assess its possible role in the pathophysiology of this disease. METHODS: The study included 54 BD patients, 31 with active BD and 23 with inactive BD as well as 18 matched healthy controls. Serum IL-33 levels were measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS: The mean serum IL-33 levels were 4.84 ± 2.81 pg/ml in the BD patients (6.16 ± 2.94 pg/ml in the active stage and 2.86 ± 0.54 pg/ml in the inactive stage) and 2.88 ± 0.42 pg/ml in the healthy controls. Serum IL-33 levels were significantly higher in patients with BD compared with the healthy controls (p < 0.01). In active Behçet patients with arthritis the mean serum IL-33 level was higher but this finding was not statistically significant (p = 0.122). CONCLUSION: IL-33 may play a significant role of in the pathogenesis of BD.

Serum pro-matrix metalloproteinase-3 as an indicator of disease activity and severity in rheumatoid arthritis: comparison with traditional markers.

Matrix metalloproteinase-3 (MMP-3) production increases in rheumatoid arthritis (RA) and has been proposed as a marker of disease activity and joint damage. The aim of this cross-sectional study is to examine the usefulness of serum proMMP-3 as an indicator of disease activity and severity in comparison with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Serum proMMP-3 was measured by a quantitative ELISA in 85 RA patients and 70 healthy subjects. Clinical and laboratory measures of disease activity and severity were obtained. Radiological joint damage was assessed by the method of Larsen. Serum proMMP-3 was significantly higher in RA patients than that in the healthy subjects. The active RA patients had significantly higher serum proMMP-3 than the inactive patients. Serum proMMP-3 was significantly correlated with some parameters of disease activity including swollen joints count, proximal interphalangeal joint score, morning stiffness, and Health Assessment Questionnaire; however, ESR and serum CRP were better correlated with all indicators of the disease activity than proMMP-3. The analysis of receiver operating characteristic supported that ESR and CRP had higher performance for reflection of activity compared to proMMP-3. There were no significant associations among Larsen score and proMMP-3, ESR, and CRP. Our results suggest that the cross-sectional measurement of serum proMMP-3 could not give additional information about RA disease activity compared to ESR and CRP, and could not give any information about joint damage.

Serum-soluble selectin levels in patients with Behçet's disease.

Soluble forms of selectins may play a regulatory role in inflammatory responses. The aim of this study was to examine the levels of serum-soluble (s) selectins in Behçet's disease (BD) patients and to evaluate the associations of these molecules to disease activity, clinical findings, and drugs taken for BD, mainly colchicine. Serum sE-, sL-, and sP-selectins levels were measured by sandwich enzyme-linked immunosorbent assay in 28 BD patients and 22 healthy subjects. The BD patients were classified according to the disease activity, clinical findings, and therapy. Ten patients were newly diagnosed and were not taking any therapy. Remainder were on colchicine (n = 18) and immunosuppressive drugs (n = 5). In BD patients, the levels of sL- and sP-selectins were significantly lower than those of healthy controls, but sE-selectin level was similar to that of the controls. The patients on the therapy had significantly lower levels of sE- and sL-selectins and insignificantly lower level of sP-selectin than the patients not receiving therapy. The BD patients with active disease had significantly higher levels of sE-, sL-, and sP-selectins compared with the patients with inactive disease. There were no significant differences in the levels of selectins between the treated active patients and inactive patients. However, the untreated patients with active disease had significantly higher selectin levels than the inactive patients. There were no significant differences in all selectin levels between the patients with or without vascular involvement. Serum sL-selectin was found to be significantly higher in patients with erythema nodosum. In conclusion, our findings suggest that the levels of soluble selectin molecules in BD patients seem to be modified by the drugs taken for BD. The colchicine therapy is associated with lower selectin levels.

The importance of alpha-fodrin antibodies in the diagnosis of Sjögren's syndrome.

OBJECTIVE: We wanted to determine the prevalence of IgA and IgG antibodies against alpha-fodrin in the patients with primary and secondary Sjögren's syndrome (SS) and also to compare with anti-Ro and anti-La antibodies in the diagnosis of SS. METHODS: We tested the prevalence of anti-alpha-fodrin IgA, IgG, anti-Ro, anti-La antibodies, anti-nuclear antibodies (ANA) and rheumatoid factor (RF) in naive patients with primary (n = 20) and secondary SS (n = 20) (Rheumatoid Arthritis [RA]+SS, n = 10; Systemic Lupus Erythematosus [SLE] + SS, n = 10), RA (n = 10), SLE (n = 10) and in healthy controls (n = 20). Salivary gland biopsies were performed in the patients with primary and secondary SS. RESULTS: In primary SS, anti-alpha-fodrin IgA, IgG, anti-Ro and anti-La antibodies were detected as 20, 10, 55 and 20% respectively. In RA + SS, anti-alpha-fodrin IgA was detected to be 10% and IgG was negative; however, anti-Ro antibodies and anti-La antibodies were found to be 40% and 20% respectively. In SLE + SS, anti-alpha-fodrin IgA was found to be 20% and IgG was found to be 10%, but anti-Ro and anti-La antibodies were found to be 90% and 20% respectively. Alpha-fodrin antibodies were not detected in RA, SLE and healthy controls. CONCLUSION: The detection of anti-alpha-fodrin antibodies by used ELISA does not give much contribution to the diagnosis of SS, and anti-Ro and anti-La are still useful serological markers in the diagnosis of SS.

A multicenter study of patients with adult-onset Still's disease compared with systemic juvenile idiopathic arthritis.

Adult-onset Still's disease (AOSD) has often been regarded as the adult spectrum of systemic juvenile idiopathic arthritis (sJIA). The present study aims to compare the clinical and laboratory features, the disease course and the response to treatment in patients having AOSD with those having sJIA. Retrospective review of all available data that were filled out by adult and paediatric rheumatologists from six centers using a standard data extraction form was performed. A total of 95 patients with AOSD and 25 patients with sJIA were recruited for the study. The frequency of fever, rash, myalgia, weight loss and sore throat was higher in patients with AOSD. The pattern of joint involvement differed slightly. Laboratory findings were similar in both groups, except that liver dysfunction and neutrophilia were more common among adults. A multiphasic pattern dominated the childhood cases, whereas the most frequent course was a chronic one in adults. Corticosteroids and methotrexate were the most commonly employed therapy; however, chloroquine was another popular therapy in the adult group. We showed a difference in the rate of clinical and laboratory features between patients with AOSD and those with sJIA. AOSD and sJIA may still be the same disease, and children may simply be reacting differently as the result of the first encounter of the putative antigens with the immune system.

A case of overlap syndrome with rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis and secondary Sjögren's syndrome.

We report an unusual case of overlap syndrome that had the coexistence of five autoimmune diseases. A 45-year-old woman initially developed seropositive erosive rheumatoid arthritis (RA) 11 years ago. She then developed progressive systemic sclerosis (PSS) (including pulmonary hypertension, esophageal dysfunction, cardiac involvement and sclerodactilitis), systemic lupus erythematosus (SLE) (including photosensitivity, nephritis, leukopenia, lymphopenia, thrombocytopenia and Coombs positive hemolytic anemia and positive anti-dsDNA), and secondary Sjögren's syndrome (SSS) in the last 7 years before she was admitted to our clinic. The patient fulfilled classification criteria for RA, SLE, PSS and SSS, as determined by American College of Rheumatology. Hypothyroidism with positive autoantibodies due to Hashimoto's thyroiditis, the beginning of which could not be defined, was coexistent with this overlap syndrome. In the literature, although overlap syndromes in different combinations were reported, we very rarely observed a complex case like this patient. In our opinion, this is the first well-documented case of RA, PSS, SLE, SSS and Hashimoto's thyroiditis existing together in the same patient. Although immunosuppressive therapy was administered, the disease rapidly deteriorated and the patient died.

Vasculitis and expression of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin in salivary glands of patients with Sjögren's syndrome.

OBJECTIVE: We investigated the relationship between clinical symptoms and the grade of histopathological damage and expression of adhesion molecules in salivary glands of patients with Sjögren's syndrome (SS). METHODS: We studied untreated and recently diagnosed patients with primary (n =20) and secondary SS [10 with SS and rheumatoid arthritis (RA); 10 with SS and systemic lupus erythematosus (SLE)] and 3 healthy controls. Salivary gland biopsies were performed in patients and controls and clinical data were obtained. Salivary gland biopsies were assessed for lymphocyte focus score and expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. In serum, antinuclear antibodies, rheumatoid factor, anti-Ro and anti-La antibodies, anti-alpha-fodrin IgA and IgG antibodies, and gamma-globulin concentrations were measured. RESULTS: In salivary gland samples, ICAM-1 was expressed on vascular endothelial cells and lymphocyte foci, while VCAM-1 was expressed on vascular endothelial cells and follicular dendritic reticulin cells. There was a positive correlation between lymphocyte focus score and ICAM-1 expression (p < 0.05). We detected correlation between expression of ICAM-1 and VCAM-1, and the expression of VCAM-1 was significantly related to vasculitis (p < 0.05). The areas of E-selectin expression and the dispersion and severity of staining were not correlated with the focus score or with patients' clinical features (p > 0.05). There was no correlation between the staining and autoantibody positivity and gamma-globulin levels. CONCLUSION: ICAM-1 may be important for lymphocyte recruitment and glandular damage and VCAM-1 may be important for the development of vasculitis in patients with SS.

Serum homocysteine level is higher in Behçet's disease with vascular involvement.

OBJECTIVE: Behçet's disease (BD) is a multisystemic inflammatory disorder of unknown etiology that is sometimes associated with thrombosis. However, the mechanism of hypercoagulability is not known. In this study, we investigated whether hyperhomocysteinemia, being a well-known risk factor for thrombosis, is also a contributing risk factor to venous and arterial thromboses of BD. METHODS: Forty-five patients with BD and 40 healthy subjects were included in the study. Sixteen patients had vascular involvement. Serum homocysteine levels were determined by fluorescence polarization immunoassay. RESULTS: In male patients, the frequency of vascular involvement was significantly higher than in females (46.7% vs 13.3%, P < 0.05). Serum homocysteine levels were significantly higher in patients with BD than healthy controls (P < 0.01), in patients with vascular involvement than those with mucocutaneous involvement (P < 0.01) and healthy controls (P = 0.001), and in male patients than in female patients (P < 0.001). There was no significant difference in homocysteine levels between the BD patients with mucocutaneous involvement and healthy subjects. In multiple regression analysis, serum homocysteine level was independently associated with thrombosis (odds ratio 1.29, P < 0.01), but male sex was not. CONCLUSIONS: This preliminary study suggests that elevated serum homocysteine levels may play some role in the development of venous and arterial thromboses in BD.

Plasma thrombomodulin levels in patients with Behçet's disease.

The plasma levels of thrombomodulin in 54 patients with Behçet's disease (BD) and 20 healthy control subjects were studied. The mean thrombomodulin (TM) level was significantly higher in active BD patients than in inactive patients and healthy controls ( P<0.001 and <0.01, respectively). Plasma TM levels did not show a significant relation with clinical manifestations. Increased plasma TM levels are associated with active disease and may reflect the presence of endothelial cell activation and/or injury.