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Objective Behcet's disease is a complex systemic inflammatory vasculitis of incompletely understood etiology. This study was undertaken to investigate genetic associations with Behcet's disease in a diverse multiethnic population. Methods A total of 9,444 patients and controls from 7 different populations were included in this study. Genotyping was performed using an Infinium ImmunoArray-24 v.1.0 or v.2.0 BeadChip. Analysis of expression data from stimulated monocytes, and epigenetic and chromatin interaction analyses were performed. Results We identified 2 novel genetic susceptibility loci for Behcet's disease, including a risk locus in IFNGR1 (rs4896243) (odds ratio [OR] 1.25; P = 2.42 x 10(-9)) and within the intergenic region LNCAROD/DKK1 (rs1660760) (OR 0.78; P = 2.75 x 10(-8)). The risk variants in IFNGR1 significantly increased IFNGR1 messenger RNA expression in lipopolysaccharide-stimulated monocytes. In addition, our results replicated the association (P < 5 x 10(-8)) of 6 previously identified susceptibility loci in Behcet's disease: IL10, IL23R, IL12A-AS1, CCR3, ADO, and LACC1, reinforcing the notion that these loci are strong genetic factors in Behcet's disease shared across ancestries. We also identified >30 genetic susceptibility loci with a suggestive level of association (P < 5 x 10(-5)), which will require replication. Finally, functional annotation of genetic susceptibility loci in Behcet's disease revealed their possible regulatory roles and suggested potential causal genes and molecular mechanisms that could be further investigated. Conclusion We performed the largest genetic association study in Behcet's disease to date. Our findings reveal novel putative functional variants associated with the disease and replicate and extend the genetic associations in other loci across multiple ancestries., National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (NIH) [R01AR070148]; NIH [U54GM104938, U19AI082714, UM1AI144292, P30AR053483, P30AR073750], Supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (NIH) grant number R01AR070148 to Dr. Sawalha. Recruitment and genotyping of the EuropeanAmerican controls was supported by NIH grants number U54GM104938, U19AI082714, UM1AI144292, P30AR053483, and P30AR073750 to Drs. Guthridge and James. This work was supported by the use of study data downloaded from the dbGaP web site, under dbGaP accession phs000272. v1.p1.

Takayasu arteritis is a rare inflammatory disease of large arteries. We performed a genetic study in Takayasu arteritis comprising 6,670 individuals (1,226 affected individuals) from five different populations. We discovered HLA risk factors and four non-HLA susceptibility loci in VPS8, SVEP1, CFL2, and chr13q21 and reinforced IL12B, PTK2B, and chr21q22 as robust susceptibility loci shared across ancestries. Functional analysis proposed plausible underlying disease mechanisms and pinpointed ETS2 as a potential causal gene for chr21q22 association. We also identified >60 candidate loci with suggestive association (p < 5 x 10(-s)) and devised a genetic risk score for Takayasu arteritis. Takayasu arteritis was compared to hundreds of other traits, revealing the closest genetic relatedness to inflammatory bowel disease. Epigenetic patterns within risk loci suggest roles for monocytes and B cells in Takayasu arteritis. This work enhances understanding of the genetic basis and pathophysiology of Takayasu arteritis and provides clues for potential new therapeutic targets., National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) [R01 AR070148]; National Institute of Arthritis and Musculoskeletal and Skin DiseasesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) [U54 AR057319, U01 AR51874 04]; National Center for Research ResourcesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Research Resources (NCRR) [U54 RR019497]; Office of Rare Diseases Research of the National Center for Advancing Translational Sciences; Imperial College, National Institute for Health Research, Biomedical Research Centre; Wellcome TrustWellcome TrustEuropean Commission [WT107881]; Medical Research CouncilUK Research & Innovation (UKRI)Medical Research Council UK (MRC)European Commission [MC_UU_00002/4], This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health grant R01 AR070148 to A.H.S. The Vasculitis Clinical Research Consortium has received support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (U54 AR057319 and U01 AR51874 04), the National Center for Research Resources (U54 RR019497), and the Office of Rare Diseases Research of the National Center for Advancing Translational Sciences. J.C.M., A.P.K., and R.M.M. acknowledge support from the Imperial College, National Institute for Health Research, Biomedical Research Centre. C.W. and G.R. acknowledge support from The Wellcome Trust (WT107881) and the Medical Research Council (MC_UU_00002/4). This work was supported by the use of study data downloaded from the dbGaP website, under dbGaP: phs000272.v1.p1, phs000431.v2.p1, phs000583.v1.p1, and phs000444.v1.p1.

WOS: 000382747100004, PubMed ID: 27458846, Background/Aims: To establish the prevalence of the single nucleotide polymorphisms (SNPs) of endoplasmic reticulum aminopeptidase 1 (ERAP1), IL-23 receptor (IL-23R), signal transducer and activator of transcription 3 (STAT-3) and Janus kinase 2 (JAK-2) in ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) in a Turkish population. Materials and Methods: A total of 562 subjects who presented at the Ankara University internal medicine departments of rheumatology and gastroenterology outpatient clinics were recruited in this study, including 365 patients with AS, 197 patients with IBD and 230 healthy controls. ERAP1, IL-23R, STAT-3 and JAK-2) were genotyped in competitive allele-specific polymerase chain reactions. Results: The ERAP1 (rs26653) polymorphism was found to increase the disease risk in patients with AS and IBD compared with the control group (p=0.02 and p=0.01, respectively). In addition, this polymorphism revealed a significant relationship with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Bath AS Functional Index (BASFI) in patients with AS (r=0.829, p

The purposes of this study were to discern imaging findings that distinguish Behçet disease from small-bowel Crohn disease, to find initial performance estimates for these findings, and to evaluate the diagnostic value of MR enterography (MRE) for detecting intestinal Behçet disease.The MRE examinations of 30 consecutively registered patients with established intestinal Behçet disease were reviewed by two blinded readers. The frequencies of MRE findings were compared with those obtained for 30 control subjects with small-bowel Crohn disease who were matched for sex and age. The performance estimates were generated with ileocolonoscopic and histopathologic findings as the reference standard.Polypoid pattern and homogeneous mural enhancement were the findings seen more frequently in Behçet disease (p = 0.000) than in Crohn disease (p = 0.003). Stricture formation, long-segment disease, and involvement of more proximal ileal segments favored small-bowel Crohn disease. The ROC AUCs for polypoid pattern and homogeneous mural enhancement in the detection of intestinal Behçet disease were 0.806 and 0.779. The accuracy of MRE was 70.00% (95% CI, 50.60-85.27%); sensitivity, 57.14% (95% CI, 34.02-78.18%), and specificity, 100% (95% CI, 66.37-100%).MRE has potential for use as a radiation-free alternative for clarifying the cause of nonspecific gastrointestinal symptoms in patients with known Behçet disease. However, additional studies are needed to determine the actual value of MRE in patients with Behçet disease and to validate the clinical usefulness of the technique in the detection of unknown intestinal Behçet disease.

This study was undertaken to evaluate the diagnostic and prognostic values of pentraxin‐3 (PTX‐3) in patients with infected diabetic foot ulcers (IDFU) as well as to assess the association between PTX‐3 levels and IDFU severity. This study included 60 IDFU patients (Group 1), 45 diabetic patients without DFU (Group 2), and 45 healthy controls. Patients with IDFU were divided into mild, moderate, and severe subgroups based on classification of clinical severity. Patients who underwent amputation were also documented. Blood samples were collected to determine PTX‐3 levels. PTX‐3 levels in healthy controls, Group 1, and Group 2 were 5.83 (3.41‐20) ng/mL, 1.47 (0.61‐15.13) ng/mL, and 3.26 (0.67‐20) ng/mL, respectively. A negative correlation between plasma PTX‐3 and glucose levels was found. There were significant differences in terms of procalcitonin (PCT) and PTX‐3 levels in the subgroup analysis of Group 1. The PTX‐3 level in patients who did or did not undergo amputation was 4.1 (0.8‐13.7) and 1 (0.6‐15.1) ng/mL, respectively. Results suggest that PTX‐3 is a particularly effective marker in patients with IDFU, both in terms of predicting disease severity and assisting in the decision to perform amputation.

Angiotensin II type 1 receptor autoantibodies (AT1R-AAs) are known to be associated with malignant hypertension, preeclampsia, and vascular rejection in kidney transplantation. They were also suspected to have pathogenetic role in vasculopathic changes in systemic sclerosis (SSc). Clinical data regarding AT1R-AAs in SSc are scarce. In this work, we will examine the relationship between serum levels of AT1R-AAs and disease manifestations. Serum samples from SSc patients and healthy controls were analyzed for AT1R-AAs by using a commercial ELISA kit. We examined the association of serum levels of AT1R-AA with disease duration, systolic pulmonary artery pressure (sPAP) measurements, and disease manifestations like cutaneous, lung and esophageal involvements, and the presence of digital ulcers in a cross-sectional manner. There was no statistically significant difference in levels of AT1R-AAs between SSc (n = 93) patients and healthy controls (n = 66) (p = 0.23). Serum levels of AT1R-AAs were not correlated with disease duration, sPAP measurements, and showed no association with disease manifestations like lung involvement, esophageal involvement, digital ulcers, and cutaneous fibrosis. In our SSc cohort, AT1R-AA serum levels were not different from healthy subjects and higher levels were not associated with any disease manifestation neither.

It was aimed to evaluate KL-6 glycoprotein levels to determine if it may be a diagnostic marker for the connective tissue diseases (CTDs) predicting CTD-related interstitial lung diseases (ILDs) (CTD-ILD) development and to examine if there was a difference between patients and healthy controls. The study included 113 patients with CTD (45 CTD without lung involvement, 68 CTD-ILD) and 45 healthy control subjects. KL-6 glycoprotein levels were analyzed with ELISA in patients and the control group. The relationship between KL-6 glycoprotein levels and CTD-ILD was assessed. In the comparison of all the groups in the study, significantly higher levels of KL-6 were determined in the CTD-ILD group than in either the CTD without pulmonary involvement group or the healthy control group (p

Background/aim: We aimed to investigate the prevalence of anti-RNA polymerase (RNAP) III and other autoantibodies in a group of Turkish patients with systemic sclerosis (SSc) and their relation with clinical features. Materials and methods: The prevalence of anti-RNAP III and other autoantibodies was analyzed in 93 patients with SSc and control groups including 86 patients with systemic lupus erythematosus (SLE) and 65 healthy subjects, respectively. Their relationship with diseases findings was assessed in a cross-sectional manner. Results: Prevalences of anti-RNAP III were 2/93 (2.2%) in SSc, 1/86 (1.2%) in SLE, and 1/65 (1.5%) in the healthy group and there was no difference among groups (P > 0.999). Anti-Sm was significantly more common in SLE patients (P < 0.001), whereas antitopoisomerase I and anticentromere protein B were significantly more common in SSc patients (P < 0.001). There was a significant association between antitopoisomerase I positivity and interstitial lung disease (P < 0.001), and interestingly there was also a significant association between anti-SS-A 52 positivity and the presence of digital ulcers in patients with SSc. Conclusion: Our data show that anti-RNAP III in SSc patients was low in frequency in a Turkish population.

Objective 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. Methods Two independent cohorts of patients with Takayasu arteritis from Turkey and North America were included in our study. The Turkish cohort consisted of 559 patients and 489 controls, and the North American cohort consisted of 134 patients and 1,047 controls of European ancestry. Genotyping was performed using the Omni1-Quad and Omni2.5 genotyping arrays. Genotyping data were subjected to rigorous quality control measures and subsequently analyzed to discover genetic susceptibility loci for Takayasu arteritis. Results We identified genetic susceptibility loci for Takayasu arteritis with a genome-wide level of significance in IL6 (rs2069837) (odds ratio [OR] 2.07, P = 6.70 × 10−9), RPS9/LILRB3 (rs11666543) (OR 1.65, P = 2.34 × 10−8), and an intergenic locus on chromosome 21q22 (rs2836878) (OR 1.79, P = 3.62 × 10−10). The genetic susceptibility locus in RPS9/LILRB3 lies within the leukocyte receptor complex gene cluster on chromosome 19q13.4, and the disease risk variant in this locus correlates with reduced expression of multiple genes including the inhibitory leukocyte immunoglobulin-like receptor gene LILRB3 (P = 2.29 × 10−8). In addition, we identified candidate susceptibility genes with suggestive levels of association (P < 1 × 10−5) with Takayasu arteritis, including PCSK5, LILRA3, PPM1G/NRBP1, and PTK2B. Conclusion Our findings indicate novel genetic susceptibility loci for Takayasu arteritis and uncover potentially important aspects of the pathophysiology of this form of vasculitis.

Introduction Churg–Strauss syndrome (CSS) is a rare multisystem vasculitis. Considering the variation of autoimmune diseases in different races, it is of interest to determine whether any outstanding features exist for Turkish patients with CSS. Objective The aim of this study was to evaluate the clinical and serological features of the disease, the treatment, and long-term follow-up details, and to investigate possible etiological factors of Turkish CSS patients. Methods The study included 14 patients who were diagnosed with CSS, and followed by our department between 2004 and 2012. Possible etiological factors, initial symptoms, clinical presentations, treatment, as well as outcomes were documented. The study was approved by the local ethics. Results All patients fulfilled the American College of Rheumatology criteria. Initial symptoms were worsening asthma (n = 14; 100%) and skin lesions (n = 6; 43%). All patients had a diagnosis of asthma and nasal polyps, whereas 57.1% had aspirin hypersensitivity at the time of diagnosis. The lungs (100%) and skin (43%) were most commonly involved. Peripheral eosinophilia dominated on initial presentations of all patients. Initial treatments included oral methyl prednisolone in all cases, whereas cyclophosphamide and azathioprine were used in three cases. Relapses were detected in five cases. None of the cases were able to stop the oral corticosteroid treatment. No fatalities were observed. Conclusion We herein describe a new severe asthma endotype in connection with CSS. We suggest that physicians who deal with uncontrolled severe asthma cases should consider CSS in the presence of nasal polyps, aspirin hypersensitivity, and especially peripheral blood eosinophilia over 10%.

We present three patients with Behçet’s disease associated with intracardiac thrombus and pulmonary vascular involvement. One of these patients had also Budd-Chiari syndrome. All patients were treated with corticosteroid plus monthly intravenous cyclophosphamide as first line treatment and with no recurrences. Immunosuppressive therapy was successful in the treatment of intracardiac thrombus and also in the regression of pulmonary vascular thromboses in these patients. Intracardiac thrombus in Behçet’s disease is rarely seen. Behçet’s disease should be remembered in the differential diagnosis of the patients with intracardiac mass, especially in patients from the Mediterranean and Middle East populations.

We present a case of a 34-year-old male who presented to the emergency ward with fever and abdominal pain. The diagnosis of Takayasu’s arteritis and also antiphospholipid syndrome was made during an imaging workup of deep-vein thrombosis. A spontaneous coronary artery dissection was revealed in coronary CT angiography requested for chest pain and dyspnea. The patient was treated medically and discharged on close followup. The concurrence of spontaneous coronary artery dissection with antiphospholipid syndrome and Takayasu’s arteritis has not been reported in the previous literature. The possibility of a spontaneous coronary artery dissection should be considered in patients presenting with both diseases.

WOS: 000399829800001, PubMed ID: 28289872, Patients with primary Sjogren's syndrome (pSS) may go undiagnosed or be misclassified due to the insidious nature and wide spectrum of the disease. The available several classification criteria emphasize glandular findings. We aimed to analyze the efficiency of various classification criteria sets in patients diagnosed on the clinical basis by expert opinion and to compare those pSS patients who fulfilled these criteria with those who did not. This is a multicenter study in which 834 patients from 22 university-based rheumatology clinics are included. Diagnosis of pSS was made on the clinical basis by the expert opinion. In this study, we only interviewed patients once and collected available data from the medical records. The European criteria, American-European Consensus Group (AECG) and American College of Rheumatology (ACR) Sjogren's criteria were applied. Majority of the patients were women (F/M was 20/1). The median duration from the first pSS-related symptom to diagnosis was significantly shorter in men (2.5 +/- 2.3 vs 4.3 +/- 5.9 years) (p = 0 < 0.016). When the European, AECG and ACR Sjogren's criteria were applied, 666 patients (79.9%) satisfied at least one of them. In total, 539 patients (64.4%) satisfied the European, 439 (52.6%) satisfied the AECG, and 359 (43%) satisfied the ACR criteria. Among the entire group, 250 patients (29.9%) satisfied all and 168 (20.1%) met none of the criteria. The rates of extraglandular organ involvements were not different between patients who met at least one of the criteria sets and those who met none. There is an urgent need for the modification of the pSS criteria sets to prevent exclusion of patients with extraglandular involvements as the dominant clinical features., Rheumatology Society of Turkey (TRD), This study was funded by the Rheumatology Society of Turkey (TRD) (award recipient is Yasemin Kabasakal, M.D.).

Angiotensin II type 1 receptor autoantibodies (AT

There are scarce clinical data regarding serum pentraxin 3 (PTX3) and fibroblast growth factor 2 (FGF2) in patients with systemic sclerosis (SSc). Study was conducted to evaluate serum levels in our SSc cohort. Serum PTX3 and FGF2 concentrations were compared among SSc, disease control (systemic lupus erythematosus (SLE)), and healthy control groups. We also examined the association of serum levels of PTX3 and FGF2 with disease manifestations. Serum PTX3 levels were similarly distributed among SSc (n = 93) and healthy groups (n = 66) (p = 1.00) while PTX3 levels were higher in SLE controls (n = 86) compared to both SSc and healthy groups. PTX3 levels were higher in limited SSc cases compared to diffuse cases (p = 0.016). Median PTX3 levels in SSc cases with lung involvement were lower compared to cases with no lung involvement (p = 0.006). Patients with SSc had significantly lower serum levels of FGF2 compared to SLE and healthy groups. Serum FGF2 concentration was undetectable in 61.3% of cases with SSc while 30.2% of SLE and only 4.5% of healthy cases had undetectable FGF2 levels (p

To establish the prevalence of the single nucleotide polymorphisms (SNPs) of endoplasmic reticulum aminopeptidase 1 (ERAP1), IL-23 receptor (IL-23R), signal transducer and activator of transcription 3 (STAT-3) and Janus kinase 2 (JAK-2) in ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) in a Turkish population.Materials and Methods: A total of 562 subjects who presented at the Ankara University internal medicine departments of rheumatology and gastroenterology outpatient clinics were recruited in this study, including 365 patients with AS, 197 patients with IBD and 230 healthy controls. ERAP1, IL-23R, STAT-3 and JAK-2) were genotyped in competitive allele-specific polymerase chain reactions. Results: The ERAP1 (rs26653) polymorphism was found to increase the disease risk in patients with AS and IBD compared with the control group (p=0.02 and p=0.01, respectively). In addition, this polymorphism revealed a significant relationship with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Bath AS Functional Index (BASFI) in patients with AS (r=0.829, p

Rheumatic heart disease (RHD) or acute rheumatic fever (ARF) develops as a consequence of an exaggerated immune response to Group A beta haemolytic streptococci causing pharyngitis. The molecular mimicry appears between human cardiac myosin and M protein of group A streptococcal membranes. The polymorphism of the protein tyrosine phosphatase nonreceptor 22 (PTPN22) gene, which encodes an important negative regulator of T cell activation, has been reported to be associated with susceptibility to several autoimmune diseases such as SLE and RA. The objective of this study was to investigate whether PTPN22 R620W polymorphism confers susceptibility to RHD in Turkish population. PTPN 22 R620W (rs2476601, A/G) polymorphism was genotyped by PCR-RFLP in 121 patients with RHD who fulfilling the revised classification criteria of Jones, and 160 healthy control (HC), and also 137 SLE as a diseased-control. The frequency of GG and AG genotypes were found to be 94% (114), 6% (7) in RHD, respectively and 96% (153) and 4% (7) in HC, respectively. The homozygous AA genotype was not present in RHD and HC. There was no statistically significant difference between RHD and HC according to the frequency of AG heterozygote genotype (P = 0.831; OR = 1.13; 95% CI 0.37-3.46). The frequency of the rare allele A was also very similar in RHD patients and HC (3, 2% respectively). A similar result was also found between SLE and HC. Our results demonstrated that the PTPN22 R620W polymorphism is not associated with RHD nor with SLE in Turkish population.

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 (p0.05; 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; p0.05). 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.

Objectives: There are controversial reports on the frequency of antiphospholipid antibodies (aPL) in patients with systemic lupus erythematosus (SLE). Thus, we aimed to determine the frequency and clinical importance of aPL isotypes in Turkish patients with SLE. Design and methods: Fifty-nine patients with SLE and 41 healthy controls were included. Serum aPL levels were measured both in patients and healthy subjects by ELISA. Results: Fifteen of the patients with SLE had the antiphospholipid syndrome (APS) (25.4%). The percentage of anticardiolipin antibody (aCL)-positive SLE patients among all patients was 56%. At least one isotype of anti-β 2 -glycoprotein I (β 2 -GPI) antibody was positive in 83% of patients. The positivity rates of aCL and anti-β 2 -GPI antibodies in patients with or without APS were higher than the healthy controls. There were positive correlations between isotypes of IgM aCL, IgG and IgM anti-β 2 -GPI and manifestations of APS. Conclusion: It seems that the isotypes of IgM aCL, IgG and IgM anti-β 2 -GPI are correlated with manifestations of APS. They may play a role in pathogenesis and may be helpful in establishing the diagnosis.

This study aims to investigate ventricular repolarization using T-peak to T-end (Tp-e) intervals and Tp-e/QT ratios in patients with systemic sclerosis (SSc).Totally 65 patients (8 males, 57 females; mean age 49.8 years; range 20 to 77 years) with SSc and 63 control subjects (8 males, 55 females; mean age 49.3 years; range 20 to 77 years) were enrolled. Tp-e intervals, Tp-e/QT, and Tp-e/corrected QT (QTc) ratios were measured from the 12-lead electrocardiogram.Tp-e intervals, QT intervals, QTc intervals, Tp-e/QT, and Tp-e/QTc ratios were significantly higher in patients with SSc than control subjects (all p0.01). There was no difference between patients with diffuse and limited cutaneous SSc in terms of electrocardiogram and echocardiographic findings. Correlation analysis revealed no correlation between Tp-e intervals, Tp-e/QT, and Tp-e/QTc ratios with disease duration and anti-Sjögren's syndrome antigen A antibody levels in patients with SSc (all p0.05).Our study showed that Tp-e intervals, Tp-e/QT, and Tp-e/QTc ratios were increased in patients with SSc than control subjects. The increased frequency of ventricular arrhythmias can be clarified by increased indexes of ventricular repolarization parameters in patients with SSc.

Romatoid Artrit (RA) terimi, ilk olarak 1876 yilinda Sir Alfred Baring Garrod tarafmdan kullanilmakla beraber, hastaligin tanim- lanmasi 1800 yilinda Landre Beauvals'e kadar uzanir. RA teriminin Amerikan Romatizma Cemiyeti (ARA) tarafmdan kabulu ise 1941 yi- lma kadar zaman almistir (15). Romatoid Artrit; kronik ve sistemik bir inflamatuvar hastalik olup, kikirdak erozyonu, kemikte hasar ve eklemlerin fibroz ankilozuna ne- den olabilen kronik bir sinovit ile karakterlidir (23). Bilinmeyen bir antijenik uyari sonrasinda geliserek eklemde harabiyet meydana ge- tiren RA ile postinfeksiyoz olarak gelisen reaktif artrit arasindaki ana patogenetik farklilik bugun tam olarak bilinmemektedir. RA'de has- taligin kronisitesi ve eklemde erozyon gelismesinde sitokinlerin onemli rolu oldugu dusunulmektedir (19). T-hucreleri ve diger immun kom- petan hucreler, antijen ile karsilastiklarinda, cevap olarak bircok im- munolojik aktif madde uretir ve salgilarlar, Bu maddelere sitokin ismi verilmektedir (22). Sitokinler; hucre gelisimini, olgunlasmasini veya fonksiyonlarini etkileyen solubl peptidlerdir. Bu sitokinlerin bir alt gurubuna da interlokin adi verilmektedir. Bir immunopeptidin inter- lokin olarak isimlendirilebilmesi icin su 3 ozellige sahip olmasi gerek- mektedir (7)

To determine the prevalence, clinical and radiological characteristics of spondyloarthropathy (SpA) in patients with inflammatory bowel disease (IBD), to assess the association between HLA B27 and B51 and the extraintestinal symptoms and to evaluate whether IBD is associated with Behçet's disease (BD). One hundred and sixty-two consecutive adult patients with established diagnosis of IBD as either Crohn's disease (CD) or ulcerative colitis (UC) were evaluated. All the patients including those previously diagnosed with or without SpA had a complete rheumatologic examination and they were evaluated according to the European Spondyloarthropathy Study Group (ESSG) criteria for SpA and The International Study Group for Behçet's disease criteria for BD. The demographic and clinical data were recorded on a standardized form. The radiographies were obtained in all the patients and computed tomography (CT) was performed in the patients with suspected pelvic radiographies and/or low back pain in the physical examination. Radiological evaluation was made according to the Modified New York criteria. HLA B27, B51 and anti-neutrophile cytoplasmic antigen (ANCA) were searched in all the patients. Of the 162 patients with IBD (mean age 41.48+/-11.63 years, male 60, female 102), 78 were CD and 84 were UC. The mean of the IBD duration was 54.92+/-50.32 months and SpA duration was 20.63+/-34.37 months. The prevalence of SpA and AS in IBD was 45.7 and 9.9%, respectively. Frequencies of SpA and AS, the difference between UC and CD were not significant. Spondylitis, enthesitis, peripheral arthritis, oral ulcer and uveitis were not different between UC and CD, but erythema nodosum was found significantly more common in the CD patients compared with UC patients (P=0.005). The duration of IBD and SpA was similar in both groups. As the IBD duration increased, the prevalence of SpA development decreased (rr=0.991, P=0.009). Of the IBD patients, 13.6% were asymptomatic for musculoskeletal manifestations of SpA and their sacroiliac radiographies and CTs showed grade 2 sacroiliitis. HLA B27, B51 and ANCA positivities were not different between the patients with UC and CD. HLA B27 was significantly more common in the patients with sacroiliitis, spondylitis, enthesitis, peripheral arthritis, erythema nodosum, uveitis (P0.001) and oral ulcer (P=0.025). BD was diagnosed in none of the patients. ANCA positivity was found to be related with the presence of erythema nodosum and uveitis (P=0.001 and P=0.005). The prevalence of SpA and AS is higher in the prospectively evaluated patients with radiological studies than those in the previously published studies. There is a high prevalence of asymptomatic sacroiliitis in IBD. An early diagnosis of inflammatory arthritis in IBD patients may prevent a disability due to SpA and AS.

Resume Objectifs. – Determiner la prevalence des anticorps anticytoplasme des polynucleaires neutrophiles (ANCA) et de leurs sous-types chez les patients atteints de polyarthrite rhumatoide (PR), et rechercher des associations entre ces anticorps et les signes cliniques, biologiques et radiologiques. Patients et methodes. – Nous avons effectue une etude transversale chez 85 patients atteints de PR, evoluant depuis 8,7 ± 6,4 ans (moyenne ± deviation standard), et suivis a l’hopital universitaire d’Ankara. Nous avons analyse les caracteristiques cliniques, biologiques et radiologiques et nous avons recherche les ANCA, les anticorps antimyeloperoxydase (MPO) et antiproteinase 3 (PR3). Resultats. – La prevalence etait de 18 % (15/85 patients) pour les ANCA, 6 % pour les ANCA a fluorescence perinucleaire (p-ANCA) et de 12 % pour les ANCA a fluorescence atypique (a-ANCA). Des anti-MPO etaient presents chez six patients, mais aucun cas de PR avec anti-PR3 n’a ete observe. Il n’a pas ete observe de correlation entre la presence d’ANCA (globalement ou sous-types) et les signes cliniques ou biologiques d’activite de la PR, ou encore les signes radiologiques. De meme, les ANCA n’etaient pas associes a la presence de signes suggerant une vascularite (notes chez 11 des 85 patients) ou a la presence d’autres manifestations extra-articulaires. Conclusion. – Nos resultats confirment la presence d’ANCA de specificites diverses (principalement des a-ANCA) chez une minorite de patients atteints de PR. Mais la presence d’ANCA n’etait pas associee avec la severite de la PR, notamment pour les six patients porteurs d’anti-MPO qui d’ailleurs n’avaient pas de signe de vascularite. La plus forte prevalence des a-ANCA, en comparaison aux p-ANCA, dans le serum des PR, meriterait d’etre analysee plus specifiquement.

Objectives. – To determine the prevalence and the associations of anti-neutrophil cytoplasmic antibodies (ANCA) and subtypes with clinical, biological, and radiological findings in patients with rheumatoid arthritis (RA). Materials and methods. – This is a transversal study of 85 patients with RA (followed in Ibn-i Sina Hospital, Ankara University School of Medicine) with disease duration of 8.7 ± 6.4 years. Besides clinical, biological, and radiological disease activity parameters, ANCA and ANCA against myeloperoxidase (MPO) and proteinase 3 (PR3) were examined. Results. – The prevalence of ANCA, perinuclear ANCA (p-ANCA) and atypical ANCA (a-ANCA) were 18% (15/85 patients), 6% and 12%, respectively. Anti-MPO was found in six patients while anti-PR3 was not found. No significant association could be found between clinical, biological, and radiological disease activity assessments and ANCA (including indirect immunoflorescence subtypes). Similarly, ANCA were not associated with features suggestive of underlying vasculitis (noticed in 11/85 patients), and/or other extra-articular features. Conclusions. – Our results confirm that ANCA of various specificities (mainly a-ANCA) occur in a minority of RA. However, those ANCA were not associated with more severe RA, including the 6/85 patients positive for MPO (who were all free from vasculitis). The over-representation in RA sera of a-ANCA, as compared to p-ANCA, should be further studied.

WOS: 000226665600001 PubMed: 14600787 Serum levels of proinflammatory cytokines interleukin-1 beta (IL-1beta), tumor necrosis factor alpha, (TNF-alpha), and their inhibitors, IL-1 receptor antagonist (IL-1ra) and soluble TNF receptor 1 (sTNFR1), were determined by enzyme-linked immunosorbent assay in 104 patients with Behcet's disease (65 active, 39 inactive) and 40 healthy controls. The levels of IL-1beta and IL-1ra were significantly higher in both active and inactive patients than in control subjects (P < 0.01 and P < 0.01, respectively). The concentrations of TNF-alpha and sTNFR1 were found to be higher in active patients than in controls (P < 0.01 and P < 0.001, respectively). There were no significant differences in the serum levels of these cytokines and their inhibitors between active and inactive patients. Significant increases in mean C-reactive protein level and erythrocyte sedimentation rate were found in patients with active vs inactive disease (P < 0.001 and P < 0.05, respectively). C-reactive protein values correlated with erythrocyte sedimentation rate but not with cytokines or their inhibitors. Our conclusion is that elevated serum TNF-alpha and sTNFR1 seem to be important inflammatory mediators in Behcet's disease. The statistically significant increase in these levels may arise from the severity of inflammation in the tissue or organ involved.

Some immunological abnormalities have been described in seronegative spondyloarthropathies (SpA). The aim of this study is to determine the serum levels of IL-1beta, TNF-alpha and IL-8, which are proinflammatory cytokines in active and inactive patients with SpA, to compare the results with those of controls and to investigate a relationship with clinical activity and acute phase proteins.Forty-two patients (34 males and eight females) and 22 healthy controls (17 M and 5 F) were included in the study. All patients fulfilled Amor criteria for the classification of SpA. Among patients 23 had active and 19 had inactive disease. IL-1beta, TNF-alpha and IL-8 were determined by enzyme-linked immunosorbent assay ( ELISA), acute phase proteins were measured by nephelometric assay.There was no statistically significant difference between mean IL-1beta levels of patient groups and controls. Serum mean TNF-a levels in active and inactive patients were significantly increased as compared to that in the controls (P0.05, P0.05, respectively). Serum mean IL-8 levels in active patients was significantly increased as compared to that in the controls and in inactive patients (P0.01, P0.01, respectively). High serum IL-8 levels correlated well with C-reactive protein and haptoglobulin, but there was no correlation between IL-1beta or TNF-alpha levels and acute phase proteins such as C-reactive protein, alpha-1 acid glycoprotein, alpha-1 antitrypsin and haptoglobulin.These results suggest that serum IL-8 may reflect clinical activity of the disease and may be helpful for monitoring patients with SpA.

Resume Objectifs. Le but de cette etude etait de connaitre les taux seriques de l’IL1-beta, du TNF-alpha et de l’IL-8 qui sont des cytokines pro-inflammatoires chez des patients ayant une SpA active ou inactive, de comparer les resultats a ceux de temoins sains et de rechercher des relations entre ces taux et l’activite de la maladie et les proteines de la phase aigue de l’inflammation. Methodes. Quarante-deux patients (34 hommes et huit femmes) et 22 controles sains (17 hommes et cinq femmes) ont ete inclus dans l’etude. Tous les patients satisfaisaient les criteres d’Amor pour les SpA. Parmi les malades, 23 avaient une maladie active et 19 une maladie inactive. Les taux d’IL1-beta, de TNF-alpha et de l’IL-8 ont ete mesures par methode ELISA et les proteines de la phase aigue par methode nephelometrique. Resultats. Il n’y avait pas de difference statistique significative concernant les taux moyens d’IL-1-beta entre les deux groupes de malades et le groupe des temoins (p > 0,005 ; p > 0,005, respectivement). Les taux moyens de TNF-alpha etaient significativement augmentes dans les deux groupes de malades comparativement au groupe temoin (p

We report on a 31-year-old female patient with systemic lupus erythematosus (SLE) for 24 years who had a past history of skin tuberculosis (lupus vulgaris), long-term corticosteroid therapy, and IgG deficiency. She presented with monoarthritis and concomitant meningitis from skin tuberculosis after 5 years. The diagnosis of joint and meningeal tuberculosis was defined with clinical symptoms – signs and typical histopathological findings of involved synovium. Clinical improvement was achieved with antituberculous therapy. Cutaneous, articular, and cerebral manifestations of tuberculosis might have been confused with some of the lupus manifestations or lupus activation. It should be kept in mind that tuberculosis may be encountered in SLE due to the nature of the underlying disease and/or its therapy. It is also worth mentioning that, in this patient, tissues involved with extrapulmonary tuberculosis were the primary areas of involvement with SLE.

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.

Behcet'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 0.05). 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.

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.

We report a case of a 47-year-old woman with Wegener's granulomatosis complicated by central diabetes insipidus. The patient had initially seronegative polyarthritis which mostly responded well to methotrexate and steroid therapy. Eight months later the patient suffered from polyuria and polydipsia. There were no abnormalities of the anterior pituitary hormones. MR images showed only loss of brightness of the posterior pituitary. Extensive evaluation of the patient revealed the presence of ANCA, in c-ANCA pattern and also PR3 positivity. Three months later findings of glomerulonephritis, as suggested by an active urine sediment and gradual proteinuria, and, finally, asymptomatic pulmonary nodules completed the clinical picture of Wegener's disease within 1 year. Renal biopsy showed crescent formation in two glomeruli, consistent with ANCA-related glomerulonephritis which showed pauci-immün depositions by direct immunofluorescence. Diabetes insipidus symptoms mostly regressed; renal and pulmonary findings completely disappeared with glucocorticoid and pulse cyclophosphamide treatment. These findings show that diabetes insipidus may rarely develop early in the disease process and ANCA positivity was directly indicative of Wegener's granulomatosis before the classic clinical signs of the disease.

Churg-Strauss syndrome (CSS) is a rare multisystem vasculitis. Considering the variation of autoimmune diseases in different races, it is of interest to determine whether any outstanding features exist for Turkish patients with CSS.The aim of this study was to evaluate the clinical and serological features of the disease, the treatment, and long-term follow-up details, and to investigate possible etiological factors of Turkish CSS patients.The study included 14 patients who were diagnosed with CSS, and followed by our department between 2004 and 2012. Possible etiological factors, initial symptoms, clinical presentations, treatment, as well as outcomes were documented. The study was approved by the local ethics.All patients fulfilled the American College of Rheumatology criteria. Initial symptoms were worsening asthma (n = 14; 100%) and skin lesions (n = 6; 43%). All patients had a diagnosis of asthma and nasal polyps, whereas 57.1% had aspirin hypersensitivity at the time of diagnosis. The lungs (100%) and skin (43%) were most commonly involved. Peripheral eosinophilia dominated on initial presentations of all patients. Initial treatments included oral methyl prednisolone in all cases, whereas cyclophosphamide and azathioprine were used in three cases. Relapses were detected in five cases. None of the cases were able to stop the oral corticosteroid treatment. No fatalities were observed.We herein describe a new severe asthma endotype in connection with CSS. We suggest that physicians who deal with uncontrolled severe asthma cases should consider CSS in the presence of nasal polyps, aspirin hypersensitivity, and especially peripheral blood eosinophilia over 10%.

Behcet's disease is an inflammatory disease characterized by recurrent oral and genital ulcers and significant organ involvement. Localizing the genetic association between HLA-B*51 and Behcet's disease and exploring additional susceptibility loci in the human leukocyte antigen (HLA) region are complicated by the strong linkage disequilibrium in this region. We genotyped 8,572 variants in the extended HLA locus and carried out imputation and meta-analysis of 24,834 variants in 2 independent Behcet's disease cohorts from 2 ancestry groups. Genotyped SNPs were used to infer classical HLA alleles in the HLA-A, HLA-B, HLA-C, HLA-DQA1, HLA-DQB1 and HLA-DRB1 loci. Our data suggest that the robust HLA-B*51 association in Behcet's disease is explained by a variant located between the HLA-B and MICA genes (rs116799036: odds ratio (OR) = 3.88, P = 9.42 x 10(-5)). Three additional independent genetic associations within PSORS1C1 (rs12525170: OR = 3.01, P = 3.01 x 10(-26)), upstream of HLA-F-AS1 (rs114854070: OR = 1.95, P = 7.84 x 10(-14)) and with HLA-Cw*1602 (OR = 5.38, P = 6.07 x 10(-18)) were also identified and replicated.

WOS: 000323186200009, PubMed ID: 23830517, 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 similar to 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 x 10(-16)) and HLA-DQB1/HLA-DRB1 (rs113452171, OR = 2.34, p = 3.74 x 10(-9); and rs189754752, OR = 2.47, p = 4.22 x 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 x 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 x 10(-8))., University of MichiganUniversity of Michigan System; Vasculitis Foundation; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [GM103510, AR053483, AI08714, AI101914]; National Institute of Arthritis and Musculoskeletal and Skin DiseasesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) [U54AR057319, U01 AR51874 04]; National Center for Research ResourcesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Research Resources (NCRR) [U54 RR019497]; Office of Rare Diseases Research of the National Center for Advancing Translational Sciences, This work was supported by funding from the University of Michigan and the Vasculitis Foundation. Procurement and genotyping of the European-American control samples was supported by the National Institutes of Health grants GM103510, AR053483, AI08714, and AI101914. The Vasculitis Clinical Research Consortium has received support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (U54AR057319 and U01 AR51874 04), the National Center for Research Resources (U54 RR019497), and the Office of Rare Diseases Research of the National Center for Advancing Translational Sciences.

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.

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) (p0.005). 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) (p0.05). 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.