Fatos Onen

Familial mediterranean fever

Familial Mediterranean fever (FMF) is the most frequent hereditary inflammatory disease characterized by self-limited recurrent attacks of fever and serositis. It is transmitted in an autosomal recessive pattern and affects certain ethnic groups mainly Jews, Turks, Arabs, and Armenians. FMF is caused by mutations in MEFV gene, which encodes pyrin. This protein is expressed mainly in myeloid/monocytic cells and modulates IL-1β processing, NF-κB activation, and apoptosis. A mutated pyrin probably results in uncontrolled inflammation. The most devastating complication of FMF is amyloidosis, leading to chronic renal failure. M694V homozygocity, male gender and the α/α genotype of serum amyloid A1 gene are the currently established risk factors for development of amyloidosis. Daily colchicine is the mainstay of the therapy for the disease, resulting in complete remission or marked reduction in the frequency and duration of attacks in most patients. It is also effective in preventing and arresting renal amyloidosis.

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)).

Assessment of disease activity and progression in Takayasu’s arteritis with Disease Extent Index-Takayasu

OBJECTIVE Disease Extent Index-Takayasu (DEI.Tak) is a new index developed for the follow-up of Takayasus arteritis (TA), assessing only clinical findings without the requirement of imaging. We investigated the effectiveness of DEI.Tak in assessing disease activity and progression by comparing with physicians global assessment (PGA) and active disease criteria defined by Kerr et al. METHODS The initial DEI.Tak forms were filled in for 145 TA patients cross-sectionally to detect the baseline damage and after 29.8 (31) months (n = 105, 144 visits) only by including the new/worsening symptoms within the past 6 months. RESULTS At baseline, all patients had a DEI.Tak >0 [mean (s.d.): 7.6 (4.2)]. At this evaluation, 62% of the patients had active, 16.2% had persistent and 21.8% had inactive disease according to the PGA. At follow-up, in 69% of the patients the DEI.Tak score was 0. However, 14% of them were accepted as having active and 17% persistent disease according to PGA. In contrast, 18% with a DEI.Tak  ≥  1 were inactive according to PGA. Patients with active or persistent disease with PGA had higher DEI.Tak compared with inactives [1.3 (1.9), 1 (1.3) vs 0.2 (0.6), respectively; P < 0.001]. According to Kerrs criteria 27% were active. The total agreement between DEI.Tak and Kerrs criteria was 94% (κ = 0.85). Compared with PGA, Kerrs criteria had a total agreement of 74% and DEI.Tak 68%. CONCLUSION During follow-up, most TA patients showed no clinical activity with DEI-Tak. Although the agreement between Kerrs criteria and DEI.Tak seemed very good, using Kerrs criteria instead of DEI.Tak increased the consistency with PGA, which could be explained by the influence of imaging data and acute-phase reactant levels on the physicians decisions.

Irritable bowel syndrome in persons who acquired trichinellosis.

BACKGROUND AND AIM:The postinfectious irritable bowel syndrome (PI-IBS) frequently follows bacterial infections. Since people suffering from PI-IBS and Trichinella spiralis–infected mice develop similar findings, this animal model has been successfully used for PI-IBS studies; however, IBS has never been studied in humans after trichinellosis. The aim of this study was to evaluate the IBS symptoms in people who had acquired trichinellosis.PATIENTS AND METHODS:A large outbreak of trichinellosis caused by Trichinella britovi occurred in Izmir, Turkey, in 2003–2004. The diagnosis of trichinellosis was confirmed by serology and muscle biopsy. After clinical and laboratory evaluations, 72 patients (38 women, 34 men, mean age 33.2 ± 10.4 yr) with trichinellosis without preexisting IBS were enrolled in the study. Noninfected people (N = 27) were used as control group. A questionnaire was developed to assess symptoms of IBS and alarm symptoms. The first interview was done face-to-face. After 2, 4, and 6 months of the first interview, the questionnaire was readministered to the patients without any information on the occurrence of a previous trichinellosis syndrome, while it was applied after a year only to the patients who had suffered IBS symptoms according to at least one of the previous interviews.RESULTS:According to Rome II criteria, PI-IBS developed in 10 of 72 (13.9%) people with confirmed trichinellosis, who had no preexisting IBS. The rate of PI-IBS was 13.9% and 13.9% at the 4th and 6th months, respectively. The symptoms of PI-IBS persisted in five of them up to 1 yr. People without trichinellosis did not develop any IBS symptoms.CONCLUSIONS:This is the first report of the development of PI-IBS after T. britovi. Consequently, IBS can be considered as a secondary syndrome induced by trichinellosis.

Body composition, insulin, and leptin levels in patients with ankylosing spondylitis

The aim of this study was to compare the effect of chronic inflammation on insulin resistance, serum leptin levels, and body composition (BC) in patients with ankylosing spondylitis (AS) and healthy controls. Twenty-eight AS patients and 17 healthy controls were included in this study. Subjects with hypertension, diabetes, hyperlipidemia, and obesity were excluded. Acute phase reactants and serum levels of glucose, insulin, lipids, and leptin were studied. BC was determined anthropometrically and by foot-to-foot body fat analyzer (BIA, bioelectrical impedance analysis). Quantitative insulin-sensitivity check index, homeostasis model assessment for insulin resistance, and McAuley indices were calculated. Spinal mobility was assessed by the Bath Ankylosing Spondylitis Metrology Index (BASMI). Patients were also evaluated with the Bath Ankylosing Spondylitis Functional Index and the Bath Ankylosing Spondylitis Disease Activity Index. Age, sex distribution, smoking status, serum lipids, insulin concentrations, and insulin resistance indices were comparable between AS patients and controls (p > 0.05). However, acute phase reactants were significantly higher and leptin levels were significantly lower in the AS patients than in controls (p < 0.05). Fat percent assessed by both BIA and anthropometrical methods was lower in the male and female AS patients than in controls, and this reduced fat level reached statistical significance for men (p < 0.05). There were significant correlations between percent body fat, body mass index, leptin, age, and BASMI (p < 0.05; r = 0.6, 0.75, 0.35, −0.41, respectively). On the other hand, body fat percent, waist-to-hip ratio, C-reactive protein, and BASMI were significantly correlated with serum leptin levels (p < 0.05; r = 0.75, −0.42, −0.52, −0.47, respectively). Chronic inflammatory condition in AS may be responsible for the reduced body fat content and lower circulating leptin concentrations. Insulin levels and insulin resistance indices seem similar in patients and controls in the absence of classic vascular risk factors.

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.

Prevalence of primary Sjogren's syndrome in Turkey: a population-based epidemiological study.

Objectives:  The aim of this study was to determine the prevalence of primary Sjogren’s syndrome (pSS) in a general Turkish population according to the latest proposed American–European Consensus Group (AECG) criteria and European‐1 (EU‐1) criteria.

Increased Prevalence of M694V in Patients With Ankylosing Spondylitis Additional Evidence for a Link With Familial Mediterranean Fever

OBJECTIVE To assess whether there is a statistically significant difference in the frequency of common MEFV allele variants in patients with ankylosing spondylitis (AS) as compared with control patients with rheumatoid arthritis (RA) and with healthy control subjects. METHODS Sixty-two patients with AS, 50 healthy control subjects, and 46 patients with RA were assessed for the presence of MEFV variants. Exon 10 was analyzed by direct sequencing. E148Q was analyzed by restriction endonuclease enzyme digestion (REED) or by direct sequencing when REED analysis failed. RESULTS The allele frequency of all MEFV variants in the AS group was significantly higher than that in the pooled control group of healthy subjects plus RA patients (15.3% versus 6.8%; P = 0.021). M694V was the only variant that was significantly more common in the AS group than in the combined or individual control groups (P = 0.026 for AS patients versus healthy controls, P = 0.046 for AS patients versus RA patient controls, and P = 0.008 for AS patients versus healthy and RA patient control groups). The carriage rate of M694V was also significantly higher in the AS patient group than in the combined control group (odds ratio 7.0, P = 0.014). Neither M694V nor any other MEFV variant showed a correlation with most of the disease-related measures examined. CONCLUSION We found an increased frequency of MEFV variants in AS patients as compared with healthy controls and with RA patient controls. This was primarily due to the presence of M694V. The roles of other exon 10 variants, as well as the relationship between the variant status and the severity and clinical course of the disease, need to be explored in further studies that include sufficiently large sample sizes.

Circulated Activated Platelets and Increased Platelet Reactivity in Patients With Behçet’s Disease:

Behçet’s disease (BD) is a multisystem disorder. Venous as well as arterial thrombosis is a common complication of BD but exact pathogenetic mechanism of the thrombotic tendency is not well known. This study aimed to evaluate circulating activated platelets and platelet reactivity in Behçet’s patients. Twenty-two Behçet’s patients (4 female, 18 male; mean age 38.6 ± 10.9 years) and 20 control subjects (8 female, 12 male; mean age 38.8 ± 9.4 years) were included. Those patients who had hypertension, hyperlipidemia, peripheral or coronary artery disease, hepatic or renal function abnormality, and who were using aspirin and other platelet-active drugs were excluded. Platelet activity and reactivity to adenosine diphosphate (ADP) were measured by whole blood flow cytometry. We assessed markers of platelet degranulation (P-selectin; CD62P) and the activated glycoprotein IIb/IIIa receptor (PAC1 binding to fibrinogen binding site) before and after stimulation with ADP. Platelet P-selectin expression was not significantly different between patients and control subjects both at baseline (p=0.420) and after stimulation (p=0.56). Baseline (p=0.001) and ADP-stimulated (p=0.003) PAC1 binding was significantly higher in Behçet’s patients than in the control group. Clinical activity has no effect on P-selectin expression and PAC1 binding. There is evidence of platelet activity and hyperreactivity in patients with BD and this may contribute to a prothrombotic state. In addition to aspirin, other antiplatelet drugs may be useful in the prevention and treatment of thrombosis in Behçet’s patients.

Quality of life in patients with Takayasu's arteritis is impaired and comparable with rheumatoid arthritis and ankylosing spondylitis patients

The aims of the study were to assess the health-related quality of life (QOL) in patients with Takayasus arteritis (TA) by two different generic QOL instruments and to compare the results with those patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and healthy controls (HC). A cross-sectional study was performed in 51 patients with TA (41 women; mean age 38.4 ± 13.5), 43 RA (36 women; 55.2 ± 9.6), 31 AS (12 women; 41.2 ± 13.1), and 75 HC (53 women; 38.8 ± 10.9). Quality of life was assessed by using Short-Form 36 (SF-36) and Nottingham Health Profile (NHP). Separate dimensions of SF-36 and NHP and physical and mental summary scores of SF-36 as well were compared between patients and control groups. Physical and mental health summary scores and all SF-36 subscales, except for social functioning, were significantly lower in patients with TA than healthy controls. No significant differences between TA, RA, and AS patients were found in all SF-36 subscales and summary scores. NHP scores for energy level, pain, emotional reactions, and physical mobility were significantly higher in TA patients than controls. All NHP subscales, except for pain, were comparable in patients with TA, RA, and AS. Pain score was worse in RA patients. The NHP scores for sleep and social isolation were not different between patients and controls. Many aspects of QOL in patients with TA are significantly impaired in comparison with local healthy controls and similar to those in patients with RA and AS.