I Fresko

Istanbul University, İstanbul, Istanbul, Turkey

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Publications (38)137.57 Total impact

  • Annals of the Rheumatic Diseases 01/2014; 72(Suppl 3):A772-A772. DOI:10.1136/annrheumdis-2013-eular.2286 · 9.27 Impact Factor
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    ABSTRACT: HLA-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 Behçet's disease and HLA-B*52 in Takayasu's 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. TAK 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. We 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). In 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.
    Arthritis research & therapy 02/2012; 14(1):R27. DOI:10.1186/ar3730 · 4.12 Impact Factor
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    ABSTRACT: Takayasu's arteritis (TA) is a chronic, rare granulomatous panarteritis of unknown aetiology involving mainly the aorta and its major branches. In this study, genetic susceptibility to TA has been investigated by screening the functional single nucleotide polymorphism (SNP) of PTPN22 gene encoding the lymphoid-specific protein tyrosine phosphatase. Totally, 181 patients with TA and 177 healthy controls are genotyped by PCR-RFLP method for the SNP rs2476601 (A/G) of PTPN22 gene. Polymorphic region was amplified by PCR and digested with Xcm I enzyme. Detected frequencies of heterozygous genotype (AG) were 5.1% (9/177) in control group and 3.8% (7/181) in TA group (P = 0.61, odds ratio: 0.75, 95% CI: 0.3, 2.0). No association with angiographic type, vascular involvement or prognosis of TA was observed either. The distribution of PTPN22 polymorphism did not reveal any association with TA in Turkey.
    Rheumatology (Oxford, England) 06/2008; 47(5):634-5. DOI:10.1093/rheumatology/ken106 · 4.44 Impact Factor
  • Clinical and experimental rheumatology 01/2008; 26 (Suppulement 50):S103-6. · 2.97 Impact Factor
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    ABSTRACT: To investigate the role of shared epitope (SE) alleles in the short-term clinical response to leflunomide for the treatment of active RA. In an open-label, multi-centre study of 16-weeks duration, 93 patients (82% female) fulfilling ARA 1987 RA criteria were treated with leflunomide (100 mg loading dose for 3 days, then 20 mg/day as the maintenance dose). The primary efficacy criterion was the response status according to the European League Against Rheumatism (EULAR) response criteria using Disease Activity Score-28 (DAS28) activity measure. SE determinations have been undertaken by polymerase chain reaction and sequence-specific oligonucleotide genotyping methods. The mean (s.d.) Disease Activity Score-28 (DAS28) was 5.1 (1.3) before the treatment, which was significantly decreased after 16 weeks [3.0 (1.1), P < 0.001]. According to the EULAR response criteria, 55 patients (59.1%) were classified as good responders. SE was positive in 51 (54.8%) of the patients, with 13 (13.9%) having SE homozygosity or carrying any two SE alleles. Among SE-positive patients, 68.6% (35/51) were good responders, compared with 47.6% (20/42) in SE negatives (P = 0.04). No difference was present according to SE hetero- or homozygosity (68.4 vs 69.2%). RF was also present significantly more frequently in the SE-positive group compared with negatives (78.4 vs 57.1%, P = 0.03). However, no significant difference was observed in the prevalence of RF positivity in patients with a good clinical response (72.7 vs 63.2%, P = 0.32). The results suggest that HLA-DRB1 SE presence may favourably affect the outcome of leflunomide monotherapy in an unselected group of RA patients with an active disease and naive to leflunomide.
    Rheumatology (Oxford, England) 12/2007; 46(12):1842-4. DOI:10.1093/rheumatology/kem278 · 4.44 Impact Factor
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    Rheumatology 08/2007; 46(7):1213-4. DOI:10.1093/rheumatology/kem103 · 4.44 Impact Factor
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    ABSTRACT: Takayasu's arteritis (TA) is a chronic arterial inflammation of unknown etiology involving mainly the aorta and its major branches. Genetic polymorphisms of cytokines are screened as susceptibility factors for TA in Turkey. A total of 94 patients with TA were investigated for the genetic polymorphisms of the interleukin genes IL12, IL2,and IL6 and were compared with 108 healthy control subjects using polymerase chain reaction-sequence-specific primer method. The frequencies of IL12B 1188 C allele (p = 0.03, OR = 1.7) and CC genotype (p = 0.007, OR = 3.7) were both higher in TA patients than in control subjects. TT genotype at IL2-330 (p = 0.006, OR = 2.4) and GG genotype at IL6-174 (p = 0.04, OR = 1.9) were more frequent in TA patients. Lower prevalence of GT genotype at IL2-330 (p = 0.005, OR = 0.4), CG genotype at IL6-174 (p = 0.001, OR = 0.4), and AG genotypes at IL6-598 (p = 0.01, OR = 0.4) were also detected. The polymorphism of IL-12 as well as IL-6 and IL-2 genes may contribute to susceptibility and pathogenesis of TA by altering cytokine production and inducing inflammation.
    Human Immunology 10/2006; 67(9):735-40. DOI:10.1016/j.humimm.2006.06.003 · 2.28 Impact Factor
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    ABSTRACT: Corticosteroids are widely used in Behçet's syndrome despite the absence of controlled studies. We assessed the effect of depot corticosteroids primarily for genital ulcers and secondarily for the other mucocutaneous manifestations of Behçet's syndrome. We randomized 86 patients who had active disease with genital ulcers to receive either intramuscular corticosteroid injections (40 mg methylprednisolone acetate) or placebo every 3 weeks for 27 weeks. Seventy-six patients (88%) completed the treatment. There were no significant differences in the mean number of genital and oral ulcers, or folliculitis between groups. The mean number of erythema nodosum lesions was less in the corticosteroid group as a whole (P = 0.0046); subgroup analyses revealed that this was significant for females (P = 0.0148) but not for males (P = 0.1). Low-dose depot corticosteroids did not have any beneficial effect on genital ulcers. However, it was useful in controlling erythema nodosum lesions, especially among the females.
    Rheumatology 04/2006; 45(3):348-52. DOI:10.1093/rheumatology/kei165 · 4.44 Impact Factor
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    ABSTRACT: It is widely appreciated that patients with systemic lupus erythematosus (SLE) get thinner and shorter hair. However little work has been done to quantitate this. We assessed hair thickness of SLE patients and compared this to that of patients with rheumatoid arthritis (RA) and healthy controls (HC). Fifty-seven female patients with SLE (mean age: 32 +/- 8 years) and 77 female patients with RA (mean age: 50 +/- 12 years) were studied along with 75 healthy women (mean age: 27 +/- 6 years). Five strands of hair were taken from each subset and mounted on glass slides. Two independent observers, blind to the sources of the hair, measured the hair strands under a light microscope, using a micrometer. Finally, the mean hair thickness between each of the three groups was calculated. The hair in both SLE and RA patients was found to be thinner than that of HC by both observers (P < 0.001). Age adjusted analysis between SLE and HC showed similar results. However, there was no significant difference in hair thickness between SLE and RA. SLE patients have thinner hair compared to HC. More studies are needed to investigate the effect of disease activity, therapy and other factors on hair diameter.
    Lupus 02/2006; 15(5):282-4. DOI:10.1191/0961203306lu2303oa · 2.48 Impact Factor
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    ABSTRACT: In order to evaluate the role of human parvovirus B19 in the etiopathogenesis of autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), synovial fluid and blood specimens were collected at 1-month intervals from 20 patients with early synovitis (ES) and 31 with RA. Blood specimens were also collected from 25 patients with SLE, 25 with osteoarthritis (OA) as the diseased control group, and 50 healthy blood donors (HBD) as the healthy control group. Detection of B19 IgM and B19 IgG were performed by enzyme-linked immunosorbent assay from serum specimens, and B19 DNA was detected by polymerase chain reaction from synovial fluid samples. B19 IgM, B19 IgG, and B19 DNA were found in the three patients of the ES group. Subsequently, two of them were diagnosed with RA and one with SLE. B19 DNA was also detected in the synovial fluid of eight patients in the RA group. Of them, all were positive for B19 IgG and half were positive for B19 IgM. B19 IgM was not detected in either of the control groups. To define the role of B19 in the etiopathogenesis and prognosis of undiagnosed arthritis and other chronic inflammatory diseases such as RA and SLE, we need broader serial and prospective studies based on clinical and laboratory collaboration. In conjunction with case reports, these studies would also serve to detect other possible factors in the etiopathogenesis of chronic inflammatory diseases.
    Rheumatology International 12/2005; 26(1):7-11. DOI:10.1007/s00296-004-0494-5 · 1.63 Impact Factor
  • Scandinavian Journal of Rheumatology 02/2005; 34(1):75-6. · 2.61 Impact Factor
  • Scandinavian Journal of Rheumatology 01/2005; 34(1):75-76. DOI:10.1080/03009740510017896 · 2.61 Impact Factor
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    ABSTRACT: This study aimed to investigate the oral health of Turkish patients with Behçet's disease (BD) and whether it is associated with the disease course. One hundred and twenty patients with BD, 35 patients with recurrent aphthous stomatitis (RAS) and 65 healthy Turkish controls (HC) were included in the study. Oral health was investigated by indices applied in a BD out-patient clinic. The mean scores of plaque, sulcus bleeding and gingival indices, probing depth and the number of extracted teeth were observed to be higher in patients with BD and RAS compared to HC (P<0.05). In the linear regression analysis, plaque index score was associated with the presence of oral ulcers and male gender. An elevated plaque index score was observed to be a significant risk factor for increased severity score in patients with BD in the logistic regression analysis (P = 0.034). Oral health is impaired in BD and associated with disease severity. Improvement of the oral health of BD patients may affect their disease course, leading to a better prognosis.
    Rheumatology 08/2004; 43(8):1028-33. DOI:10.1093/rheumatology/keh236 · 4.44 Impact Factor
  • Clinical and experimental rheumatology 01/2003; 21(6):799-800. · 2.97 Impact Factor
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    ABSTRACT: The distribution of the different HLA-B*51 suballeles among patients with Behçet's disease (BD) of German (n=33) and Turkish (n=92) origin in comparison to their presence in the respective ethnically matched healthy control groups (German: n=325, Turkish: n=93) was studied. HLA-B*51x was significantly increased in both patient groups in comparison to the controls (Germans: 58% vs. 12%, OR 9.76, P<0.001; Turkish: 75% vs. 25%, OR 9.13, P<0.001). Molecular subtyping of B*51x revealed HLA-B*51011 and B*5108 as the predominant suballeles in both patient groups and controls although with a slightly increased frequency of HLA-B*5108 in the diseased individuals. HLA-B*5105 was the only further HLA-B*51x subtype detected in one Turkish patient heterozygous also for HLA-B*5101. HLA-B*5107 although present in a Turkish as well as German control was absent in the patient groups. There was also a tendency towards a higher degree of homozygosity for HLA-B*51x in both patient groups versus the matched controls (Germans: 10% in patients vs. 2,5% in controls; Turkish: 27% in patients vs. 13% in controls). Our study further supports previous hypothesis of an association of BD with B51 suballeles which share amino-acid residues at positions 63 and 67 as well as at positions 77-83 for specific peptide binding and natural killer (NK)-cell interactions. This applies to HLA-B*5101 and B*5108, but not to HLA-B*5107 different at position 67, which could be negatively associated with BD.
    Tissue Antigens 10/2001; 58(3):166-70. · 2.35 Impact Factor
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    ABSTRACT: The distribution of the different HLA-B*51 suballeles among patients with Behçet’s disease (BD) of German (n=33) and Turkish (n=92) origin in comparison to their presence in the respective ethnically matched healthy control groups (German: n=325, Turkish: n=93) was studied. HLA-B*51x was significantly increased in both patient groups in comparison to the controls (Germans: 58% vs. 12%, OR 9.76, P<0.001; Turkish: 75% vs. 25%, OR 9.13, P<0.001). Molecular subtyping of B*51x revealed HLA-B*51011 and B*5108 as the predominant suballeles in both patient groups and controls although with a slightly increased frequency of HLA-B*5108 in the diseased individuals. HLA-B*5105 was the only further HLA-B*51x subtype detected in one Turkish patient heterozygous also for HLA-B*5101. HLA-B*5107 although present in a Turkish as well as German control was absent in the patient groups. There was also a tendency towards a higher degree of homozygosity for HLA-B*51x in both patient groups versus the matched controls (Germans: 10% in patients vs. 2,5% in controls; Turkish: 27% in patients vs. 13% in controls). Our study further supports previous hypothesis of an association of BD with B51 suballeles which share amino-acid residues at positions 63 and 67 as well as at positions 77–83 for specific peptide binding and natural killer (NK)-cell interactions. This applies to HLA-B*5101 and B*5108, but not to HLA-B*5107 different at position 67, which could be negatively associated with BD.
    Tissue Antigens 08/2001; 58(3):166 - 170. DOI:10.1034/j.1399-0039.2001.580304.x · 2.35 Impact Factor
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    ABSTRACT: To evaluate the clinical features and outcome of patients with Behçet's syndrome (BS) and amyloidosis and to assess the associated risk factors. A chart review was done to determine the frequency of amyloidosis in BS among 4000 patients. Data from 14 BS patients with amyloidosis were compared with data obtained from 718 patients with BS without amyloidosis. Multiple stepwise logistic regression analysis was used to assess the risk factors. All patients with amyloidosis presented with the nephrotic syndrome or significant proteinuria. The mean time to the onset of amyloidosis was 8.1 yr (range 3-15 yr). The mean duration of follow-up after amyloidosis was 3.4 yr (range 1-11 yr). Seven out of 14 patients were alive at the time of the evaluation. Peripheral and pulmonary arterial involvement and arthritis were associated with amyloidosis (P<0.05). Amyloidosis in BS is rare and has a 50% mortality rate at 3.4 yr (range 1-11 yr). Peripheral and pulmonary arterial involvement and arthritis seem to be the strongest predictors of amyloidosis in BS.
    Rheumatology 02/2001; 40(2):212-5. DOI:10.1093/rheumatology/40.2.212 · 4.44 Impact Factor
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    ABSTRACT: To measure the intestinal permeability in patients with Behçet's syndrome (BS) and to compare the results with those obtained from healthy and diseased controls. The study group comprised 34 patients with BS without known gastrointestinal disease. Ten patients with ankylosing spondylitis (AS), 6 with inflammatory bowel diseases (IBD), 17 with systemic lupus erythematosus (SLE), and 15 healthy subjects (HC) constituted the controls. All patients received 100 microCi (3.7 MBq) of chromium-51 EDTA ((51)Cr-EDTA) as a radioactive tracer after a 72 hour abstinence from all drugs. The percentage of the isotope excreted in a 24 hour urinary specimen was the measure of permeability. The percentage (SD) rate of excretion of (51)Cr-EDTA was 4.6 (2.6) in BS, 6 (2.4) in AS, 5.2 (1. 9) in IBD, 5.56 (1.78) in SLE, and 2.3 (1) in healthy controls. (Analysis of variance: f=6.4, p=0.0002. BS v HC, AS v HC, SLE v HC significant.) The intestinal permeability in BS was significantly more than that seen among the healthy controls. Similar results in all the diseased controls cast doubt on its specificity.
    Annals of the Rheumatic Diseases 02/2001; 60(1):65-6. · 9.27 Impact Factor
  • A Siva, I Fresko
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    ABSTRACT: Clinical and imaging data suggest that Behçet's disease (BD) can present with a variety of neurologic complications, which may be subclassified into two forms. One is attributable to small venous inflammatory disease with focal or multifocal central nervous system involvement and is seen in the majority of patients. It is designated Central Nervous System-Neuro-Behçet syndrome (CNS-NBS). The other form is due to cerebral venous sinus thrombosis and has limited symptoms and a better prognosis. It is very uncommon for these two types of involvement to occur in the same individual. It is very likely that the two major forms have different pathogeneses. Patients with small vein inflammation should be considered for aggressive treatment. A substantial number of patients in this group will have a relapsing-remitting course; for some, this will evolve into a secondary progressive course. A few patients from this group will have progressive CNS dysfunction from the onset. Acute attacks of CNS-NBS are treated with either oral prednisone (1 mg/kg/d up to 4 weeks or until improvement is observed) or high-dose intravenous methylprednisolone (IVMP), 1 g/d for 5 to 7 days. After either treatment, an oral tapering dose of glucocorticoids should be given over 2 to 3 months to avoid early relapses. Some patients may require the long-term use of low maintenance doses of glucocorticoids to prevent exacerbations. Immunosuppressive agents (eg, azathioprine, cyclosporine A, cyclophosphamide, and chlorambucil), given either alone or in different combinations (eg, azathioprine with cyclosporine) for the long-term treatment of various systemic manifestations of BD, have not been shown to prevent the development of the neurologic complications of the disease, reduce its exacerbations, or stop its progression. Immunomodulatory treatments such as interferon alfa and thalidomide have been shown to be effective in treating some of the systemic manifestations of BD, but there is no information on their effects on the development and progression of CNS-NBS. Cerebral venous sinus thrombosis in BD is treated with either intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin given together with a short course of glucocorticoids. Evidence of benefit from this treatment, however, is weak.
    Current Treatment Options in Neurology 10/2000; 2(5):435-448. · 2.18 Impact Factor
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    ABSTRACT: Behçet's syndrome (BS), originally described as a triad of oral aphthae, genital ulcerations and uveitis, is a systemic vasculitis that is prevalent in the Middle east, Far East and in the Mediterranean basin. It is characterized by a heightened state of inflammation although the main drive that initiates and sustains this is not yet elucidated. Suppression of this inflammatory state constitutes the major goal of treatment and therapy is tailored according to the specific manifestations observed. We now have considerable more insight on drug management of BS compared to 20 years ago. Particularly, within the recent past we have learned to use more rationally the agents that were already available to us. This is especially true for azathioprine, cyclosporin A, thalidomide and colchicine. Promising data are also being collected with alpha-interferon. With these agents, significant progress has been achieved in the management of uveitis and mucocutaneous symptoms but treatment issues related to thrombotic problems, major vessel involvement and neurological disease have not yet been resolved.
    Annales de medecine interne 12/1999; 150(7):576-81.

Publication Stats

572 Citations
137.57 Total Impact Points

Institutions

  • 1998–2012
    • Istanbul University
      • Department of Family Medicine (Cerrahpasa Faculty of Medicine)
      İstanbul, Istanbul, Turkey
    • IT University of Copenhagen
      København, Capital Region, Denmark
  • 2007
    • Cukurova University
      Adhanah, Adana, Turkey
  • 2004
    • Marmara University
      • Department of Oral Diagnosis and Radiology (IHS)
      İstanbul, Istanbul, Turkey