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DİRESKENELİ, RAFİ HANER

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DİRESKENELİ

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RAFİ HANER

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Now showing 1 - 10 of 48
  • PublicationOpen Access
    Humoral immune response to mycobacterial heat shock protein (hsp)65 in the cerebrospinal fluid of neuro-Behcet patients
    (BLACKWELL SCIENCE LTD, 2001-12-25) DİRESKENELİ, RAFİ HANER; Tasci, B; Direskeneli, H; Serdaroglu, P; Akman-Demir, G; Eraksoy, M; Saruhan-Direskeneli, G
    Although systemic immune reactivity to 65-kD mycobacterial hsp65 (m-hsp65) has been shown previously in Behcet's disease (BD), local immune response was not investigated. Mie studied anti-m-hsp65 IgG, IgM and IgA antibodies in the serum and cerebrospinal fluid (CSF) of 25 ED patients with cerebral parenchymal involvement (p-NBD), seven ED patients with intracranial hypertension (ih-NBD), eight BD patients without central nervous system (CNS) involvement, 30 patients with multiple sclerosis (MS) and 24 patients with non-inflammatory CNS disorders (NIC). Significantly higher CSF IgG responses were detected in p-NBD patients (ELISA ratio 1.3 +/- 0.9) compared with NIC (0.7 +/- 0.4, P < 0.01). In p-NBD patients' IgG, IgM or IgA CSF anti-m-hsp65 positivity rate was 48% (12/25); this was significantly higher when compared with MS (3/30; P < 0.03) and NIC (3/24; P < 0.01). CSF anti-m-hsp65 IgG ratios correlated with the duration of ED (r = 0.4, P < 0.04) but not with the duration of neurological involvement. Serum IBM and IgA responses were elevated in ih-NBD, suggesting a different type of involvement than p-NBD. These results implicate an increased local humoral response to m-hsp65 in the CSF of p-NBD patients, which might be related to the pathogenesis of neurological involvement.
  • Publication
    Anti-CCP antibodies in rheumatoid arthritis and psoriatic arthritis
    (SPRINGER LONDON LTD, 2007) DİRESKENELİ, RAFİ HANER; Inanc, N.; Dalkilic, E.; Kamali, S.; Kasapoglu-Gunal, E.; Elbir, Y.; Direskeneli, H.; Inanc, M.
    Our aim is to assess the prevalence and associated clinical features of anti-CCP (cyclic citrullinated peptide) antibodies for RF (rheumatoid factor)-positive and RF-negative rheumatoid arthritis (RA) and psoriatic arthritis (PsA). In a prospective, cross-sectional, multi-centre study, we determined the titres of anti-CCP antibodies in 208 RA patients (129 RF-positive, 79 RF-negative), 56 PsA patients and 39 healthy controls (HC). Clinical parameters including disease activity (disease activity score 28-DAS28), physical disability (health assessment questionnaire-HAQ), functional capacity (functional class) and radiological erosions were investigated in patients with RA. In PsA patients, clinical and radiological features were determined. Anti-CCP2 antibodies were measured using a second-generation anti-CCP enzyme-linked immunosorbent assay (Euro-Diagnostica, Netherlands). One-hundred four of 129 RF-positive RA (81%), 16 of 79 RF-negative RA (20%), seven of 56 PsA patients (12.5%) and none of the HC had anti-CCP antibodies. RA patients with anti-CCP antibodies had significantly higher disease activity, greater loss of function and more frequent erosive disease than anti-CCP antibody-negative group. In subgroup analysis, anti-CCP antibodies in RF-negative patients were also associated with erosive disease. All PsA patients with anti-CCP antibodies had symmetric arthritis with higher number of swollen joints. The prevalence of anti-CCP antibodies in RF-positive RA patients was significantly higher than in RF-negative RA and PsA patients. Anti-CCP antibodies were also associated with erosive disease in RF-negative RA patients. Both anti-CCP and RF tests were negative in 30% of the patients. Anti-CCP positivity was a frequent finding in PsA and associated with symmetrical polyarthritis.
  • PublicationOpen Access
    PTPN22 gene polymorphism in Takayasus arteritis
    (OXFORD UNIV PRESS, 2008-01-29) DİRESKENELİ, RAFİ HANER; Sahin, N.; Aksu, K.; Kamali, S.; Bicakcigil, M.; Oezbalkan, Z.; Fresko, I.; Oezer, H.; Akar, S.; Onat, A. M.; Cobankara, V.; Kiraz, S.; Oeztuerk, M. A.; Tunc, E.; Yuecel, E.; Ates, A.; Keser, G.; Inanc, M.; Direskeneli, H.; Saruhan-Direskeneli, G.
    Objective. Takayasus 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. Methods. 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. Results. 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. Conclusion. The distribution of PTPN22 polymorphism did not reveal any association with TA in Turkey.
  • PublicationOpen Access
    Behcet's disease: from innate to adaptive immunity
    (BIOMED CENTRAL LTD, 2003) DİRESKENELİ, RAFİ HANER; Direskeneli, H
  • PublicationOpen Access
    The role of HLA-DRB1 shared epitope alleles in predicting short-term response to leflunomide in rheumatoid arthritis
    (OXFORD UNIV PRESS, 2007-08-05) DİRESKENELİ, RAFİ HANER; Saruhan-Direskeneli, G.; Inanc, M.; Fresko, I.; Akkoc, N.; Dalkilic, E.; Erken, E.; Karaaslan, Y.; Kinikli, G.; Oksel, F.; Pay, S.; Yucel, E.; Yentuer, S. P.; Duymaz-Tozkir, J.; Yilmaz, V.; Inanc, N.; Yazici, H.; Konice, M.; Direskeneli, H.
    Objectives. To investigate the role of shared epitope (SE) alleles in the short-term clinical response to leflunomide for the treatment of active RA. Methods. 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 sequencespecific oligonucleotide genotyping methods. Results. 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). Conclusions. 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.
  • PublicationOpen Access
    Oligoclonal T cell expansions in patients with Behçet's disease
    (2001-12-24) DİRESKENELİ, RAFİ HANER; ERGUN, SAFİYE ATLAS TÜLİN; Direskeneli, H; Eksioglu-Demiralp, E; Kibaroglu, A; Yavuz, S; Ergun, T; Akoglu, T
    Behçet's disease (BD) is a multisystem disorder with oral and genital ulcers, mucocutaneous, ocular, joint, vascular and central nervous system involvement. In this study, the peripheral T cell repertoire was analysed in patients with BD with MoAbs against T cell receptor (TCR) Vβ gene products in CD4+ and CD8+ T cell compartments, and these were compared with rheumatoid arthritis (RA) patients and healthy controls (HC). In the CD4+ T cell compartment, oligoclonal TCR Vβ expression was observed in 56% of BD (10/18), 71% of RA (5/7) patients and 21% (3/14) of HC. In the CD8+ T cell group 50% of BD (9/18), 57% of RA patients and 28% of HC (4/14) had an oligoclonal TCR repertoire. An increase of TCR Vβ5.1 subset was observed in five BD patients among CD8+ T cells. Other elevations of TCR Vβ subsets were heterogeneously distributed with one to three different Vβ subsets. Our results suggest an antigen-driven oligoclonal increase of T cells in BD. There was no overall increase in any Vβ group to suggest a superantigen effect. Analysis of the responsible antigens causing the increase in T cell subsets may give insights into the aetiopathogenesis of BD and immunomodulation of these T cells may lead to new treatments.
  • PublicationOpen Access
    Anti-MHC autoimmunity in Behcet's disease: T cell responses to an HLA-B-derived peptide cross-reactive with retinal-S antigen in patients with uveitis
    (BLACKWELL SCIENCE LTD, 2001-12-24) DİRESKENELİ, RAFİ HANER; Kurhan-Yavuz, S; Direskeneli, H; Bozkurt, N; Ozyazgan, Y; Bavbek, T; Kazokoglu, H; Eksioglu-Demiralp, E; Wildner, G; Diedrichs-Mohring, M; Akoglu, T
    Immune response to retinal autoantigens plays a central role in the pathogenesis of uveitis. A synthetic peptide (B27PD) from a common sequence of various HLA-B molecules associated with uveitis, such as HLA-B27 and 51, which shares amino acid homologies with a retinal-S antigen (S-Ag)-derived peptide (PDSAg), was shown to be immunogenic in human and experimental uveitis in the rat. In this study we investigated T cell responses to B27PD and PDSAg in patients with Behcet's disease and posterior uveitis (BD-posterior uveitis; n = 33) in comparison with non-Behcet anterior uveitis (AU, n = 14), Behcet's patients without uveitis (BD, n = 15) and healthy controls (HC, n = 32) in a 6-day proliferation assay. Patients with BD and posterior uveitis had significantly higher responses (stimulation index (SI) 2.8 +/- 1.3) than those with AU (SI 1.5 +/- 0.4), BD without uveitis (SI 1.1 +/- 0.4) and HC (SI 1.1 +/- 0.6) for B27PD (P < 0.0001). Responses to PDSAg were also higher in BD with posterior uveitis patients (SI 3.3 +/- 1.6) than AU (SI 1.5 +/- 0.4), BD without uveitis (SI 1.2 +/- 0.3) and HC (SI 1.1 +/- 0.6) (P < 0.0001). A significant correlation between the responses to PDSAg and B27PD (r = 0.56, P < 0.001) was observed. Elevated levels of IL-2 and tumour necrosis factor-alpha were also observed in culture supernatants obtained from peripheral blood mononuclear cells after stimulation with the peptides, but no correlation was found between the proliferative responses and cytokine levels. These results suggest that cellular immunity to cross-reactive HLA-B and S-Ag-derived peptides might play a role in the pathogenesis of posterior uveitis in BD.
  • PublicationOpen Access
    Autoimmunity vs autoinflammation in Behcet's disease: do we oversimplify a complex disorder?
    (OXFORD UNIV PRESS, 2006-08-18) DİRESKENELİ, RAFİ HANER; Direskeneli, H.
    Behcet's disease (BD) is a systemic inflammatory disorder with a diverse spectrum of clinical manifestations including mucocutaneous, ocular, vascular, gastrointestinal, musculoskeletal and central nervous system involvement [1]. A complex genetic background leading to a pro-inflammatory, innate-immune-system-derived activation perpetuated by adaptive immune responses against enviromental and auto-antigens is accepted to be the hallmark of BD [2]. This review aims to make an in-depth critical analysis of current data for recent controversies on the role of innate immune system vs autoimmunity in BD [3-5].
  • Publication
    No association of PTPN22 gene polymorphism with rheumatoid arthritis in Turkey
    (SPRINGER HEIDELBERG, 2009) GÜNDÜZ, FEYZA; Sahin, N.; Gunduz, F.; Inanc, N.; Direskeneli, Haner; Saruhan-Direskeneli, G.
    Although the association of rheumatoid arthritis (RA) with HLA-DRB1 (shared epitope) is well demonstrated in many ethnic populations, the role of other RA-associated risk loci is not clarified. In this study, the functional single nucleotide polymorphism (SNP) of PTPN22 gene was investigated in Turkey. 167 patients with RA and 177 healthy controls are genotyped by polymerase chain reaction (PCR)-RFLP for the SNP (rs2476601, A/G) of PTPN22 gene. Polymorphic region was amplified by PCR and digested with Xcm I enzyme. Heterozygous genotype (AG) was present in 5.1% (9/177) of the controls and in 6.6% (11/167) of RA group (p = 0.55, OR 1.3, 95% CI 0.53-3.26). There was also no association between any clinical feature, RF positivity and presence of this SNP. In conclusion, the distribution of PTPN22 polymorphism did not reveal any association with RA in Turkey.
  • PublicationOpen Access
    Early response to immunosuppressive therapy predicts good renal outcome in lupus nephritis lessons from long-term followup of patients in the Euro-Lupus Nephritis Trial - Lessons from long-term followup of patients in the Euro-Lupus Nephritis Trial
    (WILEY, 2004-12) DİRESKENELİ, RAFİ HANER; Houssiau, FA; Vasconcelos, C; D'Cruz, D; Sebastiani, GD; Garrido, ED; Danieli, MG; Abramovicz, D; Blockmans, D; Mathieu, A; Direskeneli, H; Galeazzi, M; Gul, A; Levy, Y; Petera, P; Popovic, R; Petrovic, R; Sinico, RA; Cattaneo, R; Font, J; Depresseux, GV; Cosyns, JP; Cervera, R
    Objective. In the Euro-Lupus Nephritis Trial (ELNT), 90 patients with lupus nephritis were randomly assigned to a high-dose intravenous cyclophosphamide (IV CYC) regimen (6 monthly pulses and 2 quarterly pulses with escalating doses) or a low-dose IV CYC regimen (6 pulses of 500 mg given at intervals of 2 weeks), each of which was followed by azathioprine (AZA). After a median followup of 41 months, a difference in efficacy between the 2 regimens was not observed. The present analysis was undertaken to extend the followup and to identify prognostic factors. Methods. Renal function was prospectively assessed quarterly in all 90 patients except 5 who were lost to followup. Survival curves were derived using the Kaplan-Meier method. Results. After a median followup of 73 months, there was no significant difference in the cumulative probability of end-stage renal disease or doubling of the serum creatinine level in patients who received the low-dose IV CYC regimen versus those who received the high-dose regimen. At long-term followup, 18 patients (8 receiving low-dose and 10 receiving high-dose treatment) had developed permanent renal impairment and were classified as having poor long-term renal outcome. We demonstrated by multivariate analysis that early response to therapy at 6 months (defined as a decrease in serum creatinine level and proteinuria <1 gm/24 hours) was the best predictor of good long-term renal outcome. Conclusion. Long-term followup of patients from the ELNT confirms that, in lupus nephritis, a remission-inducing regimen of low-dose IV CYC followed by AZA achieves clinical results comparable with those obtained with a high-dose regimen. Early response to therapy is predictive of good long-term renal outcome.