Genetic Association of a Gain-of-Function IFNGR1 Polymorphism and the Intergenic Region LNCAROD/DKK1 With Behcet's Disease

Objective. Behçet’s disease is a complex systemic inflammatory vasculitis of incompletely understood etiology. This study was undertaken to investigate genetic associations with Behçet’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 Behçet’s disease, including a risk locus in IFNGR1(rs4896243) (odds ratio [OR] 1.25; P = 2.42 × 10−9) and within the intergenic region LNCAROD/DKK1 (rs1660760) (OR 0.78; P = 2.75 × 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 30 genetic susceptibility loci with a suggestive level of association (P < 5 × 10−5), which will require replication. Finally, functional annotation of genetic susceptibility loci in Behçet’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 Behçet’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

Analysis of the common genetic component of large-vessel vasculitides through a meta- Immunochip strategy

Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1/HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P?=?7.54E-07; ORGCA?=?1.19, ORTAK?=?1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (PGCA?=?5.52E-04, ORGCA?=?1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus

Kollagen vasküler hastalıklarda cilt biyopsisinin direkt immünoflerasan yöntemle incelenmesi total antinükleer antikorlar ve elisa yöntemiyle anti-DNA antikorlarının ölçülmesi

TEZ55Tez (Uzmanlık) -- Çukurova Üniversitesi, Adana, 1980.Kaynakça (s. 64-75) var.75 s. : res. ; 32 cm.

Immune complexes and their relation with disease activity in systemic lupus erythematosus

Jmmün kompleks hastalıklarının prototipi olan SLE de klinik aktiviteyi tanımlamak için çeşitli otoantikorlar, kompleman ürünleri ve klinik aktivite indeksleri kullanılmıştır. Bu çalış-mada aktivite kriteri olarak, klinik bulgu ve belirtilerle beraber çift sarmallı anti-DNA anti-korları kullanılmak suretiyle lupuslu 50 aktif hasta (3 erkek, 47 kadın) ve bunlardan onunun inaktif dönemlerinde alınmış serumlarında C1q-bağlayan immün kompleksler araştırıldı. Kontrol grubu olarak 30 sağlıklı kişi (3 erkek, 27 kadın) kullanıldı. Hastaların yaş ortalaması 29.2, kontrollann 33.1 idi. C1q-bağlayan immün komplekslerin tayininde ELISA; ANA ve çift sarmallı anti-DNA antikorlarının tayininde indirekt floresan antikor yöntemi kullanıldı. Aktif ve inaktif lupuslu hastalarda C1q-bağlayan immün kompleks düzeyleri kontrol grubuna göre önemli miktarda artmıştır (p 0.05). Sonuç olarak, lupuslu hastalarda sağlıklı kontrollara göre önemli oranda artmış olmasına rağmen, serum C1q-bağlayan immün kompleks değerleri ile çift sarmallı anti-DNA antikorlarına göre tanımlanan klinik aktivite arasında ilişki bulunmamıştır. Avmün komplekslerin lupusun aktivitesi ile ilişkisini araştıran diğer çalışmalar da çelişkili sonuçlar vermiştir. Bunda kullanılan yöntemlerin farflılığı yanında, immün komplekslerin oluşmasında etkili olan fatörlerin çokluğu da etken olabilir

Serum ICAM-1 levels in kidney transplantation

Purpose: Intercellular adhesion molecule-1 (ICAM-1) is a member of immunoglobulin superfamily and acts as a ligand for the LFA-1 which is a leukocyte integrin. ICAM-1 has a role in the pathogenesis of various inflammatory processes and allograft rejection in kidney and heart transplantation. The aim of this study is to compare the serum ICAM-1 levels of kidney recipients with chronic rejection, recipients with functioning renal allografts and healthy controls. Methods: In this prospective study, serum ICAM-1 values of the 31 kidney transplantation patients (15 with normally functioning grafts and 16 with chronically rejected grafts) and 21 healthy controls were determined with ELISA method. Triple drug immunosuppressive regimen (cyclosporine + azathioprine + methylprednisolone) was given to the patients with kidney grafts. Results: The mean serum ICAM-1 level of the patients with chronic rejection (379.5±244.3 ng/ml) was higher than that of patients with functioning grafts (268.8±88 ng/ml). Although this difference was found to be statistically insignificant (p=0.057), it was close to the significancy limit. There was no statistically significant difference between the serum ICAM-1 levels of the patients either with chronic rejection or functioning grafts and those of healthy controls (307.3±63.6 ng/ml) (p=0.96 and p=0.07 respectively). Conclusion: Our findings suggest that, normal serum levels of ICAM-1 in patients with functioning grafts may be a result of proper immunosuppression. Elevated serum ICAM-1 levels in patients with chronic graft rejection indicate an activation in the immune system. We can conclude that serum ICAM-1 level measurement is not a specific parameter for detection of chronic renal graft rejection.Purpose: Intercellular adhesion molecule-1 (ICAM-1) is a member of immunoglobulin superfamily and acts as a ligand for the LFA-1 which is a leukocyte integrin. ICAM-1 has a role in the pathogenesis of various inflammatory processes and allograft rejection in kidney and heart transplantation. The aim of this study is to compare the serum ICAM-1 levels of kidney recipients with chronic rejection, recipients with functioning renal allografts and healthy controls. Methods: In this prospective study, serum ICAM-1 values of the 31 kidney transplantation patients (15 with normally functioning grafts and 16 with chronically rejected grafts) and 21 healthy controls were determined with ELISA method. Triple drug immunosuppressive regimen (cyclosporine + azathioprine + methylprednisolone) was given to the patients with kidney grafts. Results: The mean serum ICAM-1 level of the patients with chronic rejection (379.5±244.3 ng/ml) was higher than that of patients with functioning grafts (268.8±88 ng/ml). Although this difference was found to be statistically insignificant (p=0.057), it was close to the significancy limit. There was no statistically significant difference between the serum ICAM-1 levels of the patients either with chronic rejection or functioning grafts and those of healthy controls (307.3±63.6 ng/ml) (p=0.96 and p=0.07 respectively). Conclusion: Our findings suggest that, normal serum levels of ICAM-1 in patients with functioning grafts may be a result of proper immunosuppression. Elevated serum ICAM-1 levels in patients with chronic graft rejection indicate an activation in the immune system. We can conclude that serum ICAM-1 level measurement is not a specific parameter for detection of chronic renal graft rejection

Anti-chlamidial antibody levels in Behçet's disease

Bakteriolojik olarak henüz izole edilememiş olmasına rağmen. Behçet hastalığında bakteriel antijenlerin ve ısı sok proteinlerinin etyopatogenetık rolünün olabileceği bildirilmiştir. Bu çalışmada klinik ve immünolojik özellikleri bakımından Reiter sendromu ve diğer spondilartropatilerle bazı benzerlikler gösteren Behçet hastalığında klamidial enfeksiyonların rolü araştırıldı, hternasyonel Çalışma Grubu kriterlerine uygun olarak tanısı konan 33 Behçet'ti hasta ve 33 sağlıklı kontrolda serumda klamidial antikor düzeyleri solid faz enzim immunoassay yöntemi ile ölçüldü. Bu antikorların ortalama düzeyi Behçet'ti hastalarda 8.4±6.07 EUSA üniti, kontrollarda 10.3±14.21ELISA üniti olup aradaki fark önemli değildir (p>0.05). Reiter sendromunda spondilartrojenik HLA-B27 alt grupları olan B*2705, B*2701, B*2702, B*2704, B*2707 dışında kalan vakalarda bu antijenlerle kros reaktif olan (B7-Creg) B7, B40 (B60 veya B61), B22 (B54, B55, B56) ve/veya B42 grubu antijenlere raslanması ve bu grubun içinde Behçet hastalığının karakteristiği olan HLA-B5 (B*5101) in bulunmaması, bu hastalıkta farklı antijenik determinantların dolayısıyla farklı patojenlerin rolünün olabileceğini düşündürmetedir

Churg-Strauss Syndrome Associated with Montelukast: Three Case Reports

Churg-Strauss Sendromu yeni adıyla Eozinofilik Granülomatosis ve Polianjiitis; astım, ateş, periferik kanda eozinofili, eozinofilik doku infiltrasyonu, küçük ve orta çaptaki damarların nekrotizan granülomatöz inflamasyonu ile karakterize multisistemik bir hastalıktır. ANCA ilişkili vaskülitler içinde sınıflandırılmaktadır. Lökotrien reseptör antagonistleri (montelukast, zafirlukast, pranlukast), inhaler glukokortikoidler, omalizumab, kokain ve klaritromisin gibi ilaçlarla ilişkili olduğu düşünülen Churg-Strauss Sendromu vakaları bildirilmiştir. Bu makalede montelukast ilişkili nadir görülen 3 CSS olgusu sunulmuşturChurg-Strauss syndrome (new name Eosinophilic granulomatosis and polyangiitis); asthma, fever, peripheral blood eosinophilia, eosinophilic tissue infiltration, small and medium sized arteries characterized by necrotizing granulomatous inflammation is a multisystemic disorder. Classified in ANCA associated vasculitis. The drugs such as leukotriene receptor antagonists (montelukast, zafirlukast, pranlukast), inhaled glucocorticoids, omalizumab, cocaine and clarithromycin is thought to be associated with Churg-Strauss Syndrome cases have been reported. Herein we presented a rare three CSS cases associated with montelukas

INVESTIGATION OF THE FREQUENCY OF FC GAMMA RECEPTOR IIIA V/158/F GENE POLYMORPHISM AND COMPARISON OF CLINICAL AND LABORATORY FINDINGS IN RHEUMATOID ARTHRITIS (RA)

WOS: 000455121400005Objective: Rheumatoid Arthritis (RA) is a chronic multisystem disease with unknown etiology that progressively affects peripheral joints. Receptors, which serve as links between humoral and cellular immune responses, recognize the Fc region of immunoglobulin G (FcR) and have become the focus of many research studies concerning the etiology and pathogenesis of autoimmune diseases. This region displays extensive genetic variation, which has been associated with susceptibility to various chronic inflammatory disorders including RA. This study aimed to investigate the frequency of the Fc gamma RIIIA V158F genetic polymorphism and compare clinical and laboratory findings in RA. Materials and Methods: Between April 2010 and June 2011, 105 patients, who had been diagnosed with RA according to the American Rheumatology Association (ARA) diagnostic criteria, were admitted to the Cukurova University Department of Rheumatology outpatient clinic and 110 healthy controls were included in this study. Patient groups were divided into stages using the ARA functional classification. The Fc gamma RIIIA V158F gene polymorphism of patients was investigated from blood samples using the real-time Polymerase Chain Reaction (PCR) method. Results: There was no significant difference in the distribution of the Fc gamma RIIIA polymorphism between patients and controls (p=.106). There were no significant differences between the distribution of age at diagnosis of patients with the gene polymorphism (p=.919) or in the gene polymorphism (p=.552). No association was found between the gene polymorphism and clinical signs of disease such as eye involvement and the presence of rheumatoid nodules. There was also no significant association between the gene polymorphism with rheumatoid factor, anticyclic citrullinated peptide, and antinuclear antibodies (p=.625, p=.136, p=.716, respectively). Conclusion: In our study, no significant relationship was found between the Fc gamma RIIIA V158F gene polymorphism and the pathogenesis of RA.Cukurova University Scientific Research ProjectThis study has received financial support by Cukurova University Scientific Research Project

Reactive Arthritis

Reactive arthritis is an acute, sterile, non-suppurative and inflammatory arthropaty which has occured as a result of an infectious processes, mostly after gastrointestinal and genitourinary tract infections. Reiter syndrome is a frequent type of reactive arthritis. Both reactive arthritis and Reiter syndrome belong to the group of seronegative spondyloarthropathies, associated with HLA-B27 positivity and characterized by ongoing inflammation after an infectious episode. The classical triad of Reiter syndrome is defined as arthritis, conjuctivitis and urethritis and is seen only in one third of patients with Reiter syndrome. Recently, seronegative asymmetric arthritis and typical extraarticular involvement are thought to be adequate for the diagnosis. However, there is no established criteria for the diagnosis of reactive arthritis and the number of randomized and controlled studies about the therapy is not enough. [Archives Medical Review Journal 2013; 22(3.000): 283-299