Aşkın Ateş

Characteristics of vascular involvement in Behçet's disease.

Objective: Behçets 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.

Identification of multiple genetic susceptibility loci in Takayasu arteritis

Takayasu arteritis is a rare inflammatory disease of large arteries. The etiology of Takayasu arteritis remains poorly understood, but genetic contribution to the disease pathogenesis is supported by the genetic association with HLA-B*52. We genotyped ~200,000 genetic variants in two ethnically divergent Takayasu arteritis cohorts from Turkey and North America by using a custom-designed genotyping platform (Immunochip). Additional genetic variants and the classical HLA alleles were imputed and analyzed. We identified and confirmed two independent susceptibility loci within the HLA region (r(2) < 0.2): HLA-B/MICA (rs12524487, OR = 3.29, p = 5.57 × 10(-16)) and HLA-DQB1/HLA-DRB1 (rs113452171, OR = 2.34, p = 3.74 × 10(-9); and rs189754752, OR = 2.47, p = 4.22 × 10(-9)). In addition, we identified and confirmed a genetic association between Takayasu arteritis and the FCGR2A/FCGR3A locus on chromosome 1 (rs10919543, OR = 1.81, p = 5.89 × 10(-12)). The risk allele in this locus results in increased mRNA expression of FCGR2A. We also established the genetic association between IL12B and Takayasu arteritis (rs56167332, OR = 1.54, p = 2.18 × 10(-8)).

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.

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

ObjectiveBehçet’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.MethodsForty-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.ResultsIn 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.ConclusionsThis preliminary study suggests that elevated serum homocysteine levels may play some role in the development of venous and arterial thromboses in BD.

Takayasu's arteritis is associated with HLA-B*52, but not with HLA-B*51, in Turkey

IntroductionHLA-B*51 and HLA-B*52 are two close human leukocyte antigen (HLA) allele groups with minor amino acid differences. However, they are associated with two different vasculitides (HLA-B*51 in Behçets disease and HLA-B*52 in Takayasus arteritis (TAK)) and with major clinical and immunological differences. In this study, we aimed to screen a large cohort of TAK patients from Turkey for the presence of HLA-B*51 and HLA-B*52 as susceptibility and severity factors.MethodsTAK patients (n = 330) followed at a total of 15 centers were included in the study. The mean age of the patients was 37.8 years, and 86% were women. DNA samples from the patients and healthy controls (HC; n = 210) were isolated, and the presence of HLA-B*51 or HLA-B*52 was screened for by using PCR with sequence-specific primers.ResultsWe found a significant association of HLA-B*52 with TAK (20.9% vs HC = 6.7%, P = 0.000, OR = 3.7, 95% CI = 2.02 to 6.77). The distribution of HLA-B*51 did not differ between TAK patients and HCs (22.7% vs 24.8%, OR = 0.9, 95% CI = 0.60 to 1.34). The presence of HLA-B*52 decreased in late-onset patients (> 40 years of age; 12.0%, P = 0.024, OR = 0.43, 95% CI = 0.20 to 0.91). Patients with angiographic type I disease with limited aortic involvement also had a lower presence of HLA-B*52 compared to those with all other disease subtypes (13.1% vs 26%, P = 0.005, OR = 0.43, 95% CI = 0.23 to 0.78).ConclusionsIn this study, the previously reported association of TAK with HLA-B*52 in other populations was confirmed in patients from Turkey. The functional relevance of HLA-B*52 in TAK pathogenesis needs to be explored further.

Erosive arthritis in a patient with Behçet's disease

We report on a 35-year-old female patient suffering from Behçets disease for 20 years who developed recurrent oral ulcerations during the onset of the disease. This was followed by recurrent genital ulcerations and joint symptoms involving knee, wrist and feet joints and bilateral heel pain. X-rays of the feet revealed erosive and destructive changes in the 1st metatarsophalangeal and 1st proximal interphalangeal joints of the right foot and enthesopathy on calcaneus. A literature review indicated that erosive arthritis is a rare event in Behçets disease.

HLA-DRB1 genes and disease severity in rheumatoid arthritis in Turkey.

Objective: Association with human leukocyte antigen (HLA)‐DRB alleles, implicated in the aetiopathogenesis of rheumatoid arthritis (RA), is found to be different in various ethnic groups. This study aimed to investigate DRB1 alleles in RA patients in Turkey, and to examine the effect of these alleles on disease severity. Methods: We performed PCR‐based DRB1 genotyping of 104 RA patients recruited from clinical settings and 110 healthy controls. HLA DRB1 alleles frequencies in RA patients and healthy controls were determined. Phenotype frequencies of patients and controls were compared. Disease severity was assessed by radiological erosion, presence of extra‐articular involvement, and functional index. Results: Significant differences were in the frequencies of DRB1*04 (46.2% versus 20.9%, p<0.001), DRB1*0401 (10.6% versus 0%, p<0.001), DRB1*0405 (8.7% versus 0%, p=0.001), DRB1* 0404 (15.4% versus 3.6%, p<0.01), DRB1*01 (21.2% versus 10.9%, p<0.05) and DRB1*0101 (16.3% versus 5.5%, p = 0.01) between RA patients and controls. HLA‐DRB1 alleles did not show any association with seropositivity, extra‐articular involvement, radiological erosion, or functional index. Conclusion: Our results suggest that the HLA‐DRB1 alleles, particularly HLA‐DRB1*04 and subtypes, were associated with RA.

Serum‐Soluble Selectin Levels in Patients with Rheumatoid Arthritis and Systemic Sclerosis

Soluble forms of selectins may play a regulatory role in inflammatory responses that are key to the pathophysiology of rheumatic diseases such as rheumatoid arthritis (RA) and systemic sclerosis (SSc). The aim of this study was to examine whether the elevated serum‐soluble (s) selectin levels are associated with RA or SSc. Serum sE‐, sL‐ and sP‐selectin levels were measured by sandwich enzyme‐linked immunosorbent assay in 34 RA patients, 30 SSc patients and 16 healthy subjects. The levels of sE‐selectin were significantly higher in RA and SSc patients than those in healthy subjects. The sL‐selectin level was significantly lower in RA patients compared to healthy subjects. Serum sP‐selectin levels were not significantly different among the study groups. The active RA patients had significantly higher serum sE‐ and sL‐selectin levels compared to inactive RA patients. Also, some correlations were observed between the serum selectin levels and measures of disease activity such as erythrocyte sedimentation rate and C‐reactive protein in RA patients. The higher levels of sE‐selectin were found in SSc patients with pulmonary fibrosis, and there was also a negative correlation between diffusion capacity for carbon monoxide and serum sE‐selectin. Serum levels of selectins may provide a useful additional marker for disease activity in RA patients and for disease severity in SSc patients.

Identification of Susceptibility Loci in IL6, RPS9/LILRB3, and an Intergenic Locus on Chromosome 21q22 in Takayasu Arteritis in a Genome-Wide Association Study

Takayasu arteritis is a rare large vessel vasculitis with incompletely understood etiology. This study was undertaken to perform the first unbiased genome‐wide association analysis of Takayasu arteritis.

The levels of serum-soluble Fas in patients with rheumatoid arthritis and systemic sclerosis

Different defects in Fas/APO-1 interaction with its ligand or in signaling of apoptosis may contribute to autoimmune disease. The aim of this study was to examine whether elevated serum-soluble Fas (sFas) levels are associated with rheumatoid arthritis (RA) or systemic sclerosis (SSc). sFas level was assayed using a sandwich ELISA in serum from 37 patients with RA, 30 patients with SSc and 20 healthy controls. The RA patients were classified according to disease activity, anatomical joint damage, and the presence of pulmonary involvement. Presence of pulmonary fibrosis, CO diffusion capacity (DLCO) and skin score were determined in patients with SSc. Serum sFas levels were not significantly different between study groups. Serum sFas level in the active RA patients was significantly higher than in the patients with inactive disease (p<0.05). The untreated active RA patients had significantly higher sFas level than healthy controls (p<0.05). In RA patients, sFas level was significantly correlated with rheumatoid factor titer (p=0.01), C-reactive protein (p<0.05), and erythrocyte sedimentation rate (p<0.05). The RA patients with severe joint damage had significantly higher sFas level than those with mild joint damage (p<0.05). The untreated SSc patients had significantly higher sFas levels than the treated SSc patients and healthy controls (p<0.01). Serum sFas level was not correlated with presence of pulmonary fibrosis, DLCO or skin score. The soluble Fas molecule may provide a useful additional marker for assessment of disease activity and severity in patients with RA.