Muge Bicakcigil

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)).

Comparative Performance Analysis of 4 Different Anti-Citrullinated Protein Assays in the Diagnosis of Rheumatoid Arthritis

Objective. To evaluate the diagnostic performances of 2 recently developed assays, third-generation anti-cyclic citrullinated peptide (anti-CCP3) and anti-mutated citrullinated vimentin (anti-MCV), in comparison to conventional second-generation anti-cyclic citrullinated peptide (anti-CCP2) assay; and to assess a novel fully automated, random-access AxSYM anti-CCP assay for early diagnosis of rheumatoid arthritis (RA). Methods. A cohort of 176 patients was enrolled in our study; 93 were diagnosed as having RA. The non-RA group consisted of 83 patients including 38 with systemic lupus erythematosus, 17 with primary Sjögren’s syndrome, 11 with osteoarthritis, and 17 healthy controls. All were tested for presence of anti-CCP2, anti-CCP3, AxSYM anti-CCP, anti-MCV, and rheumatoid factor (RF)-IgM according to the manufacturers’ instructions. Results. Diagnostic performance of the assays revealed the highest area under the curve for the novel AxSYM anti-CCP [89.1; 95% confidence interval (CI) 84.3–93.8], followed by anti-CCP3 (86.7; 95% CI 81.6–91.9), anti-CCP2 (82; 95% CI 75.8–88.3), and anti-MCV (71.9; 95% CI 64.4–79.5). The sensitivities and specificities were 60.2% and 98.8% for anti-CCP2, 61.3% and 97.6% for anti-CCP3, 80.6% and 84.3% for AxSYM anti-CCP, 49.8% and 91.6% for anti-MCV, and 67.8% and 91.6% for RF-IgM, respectively. Conclusion. At cutoff of 5 U/ml, AxSYM anti-CCP emerged as a highly sensitive first-line early diagnostic tool for RA, with the greatest discrimination power, above 16 U/ml, in case of positive result. Using a single easily performed automated assay at 2 determined decision limits we were able to diagnose 81% of cases of RA and missing only 1.2%.

Tear Osmolarity Measurements in Dry Eye Related to Primary Sjögren’s Syndrome

Background: To evaluate the tear osmolarity in patients with dry eye syndrome related to primary Sjögren’s Syndrome (SS). Materials and Methods: Twenty eyes of 10 patients with dry eye and primary SS (Group 1) and 20 eyes of 20 subjects who do not have dry eye syndrome (Group 2) were included in this cross-sectional study. In all eyes, ophthalmic examination was performed in the same order: International Ocular Surface Disease Index survey, visual acuity assessment, conjunctival hyperemia scoring, tear osmolarity measurement with TearLab™ Osmolarity System, tear film break-up time assessment, corneal fluorescein staining scoring, ocular surface Lissamine Green staining scoring, anesthetized Schirmer test. Dry eye severity was graded according to Dry Eye Workshop (DEWS) classification system. Results: Four eyes with grade 1, four eyes with grade 2, seven eyes with grade 3, and five eyes with grade 4 dryness, according to DEWS system, were included. The mean tear osmolarity value was 301.9 ± 11.40 mOsm/L (range: 290–328) in Group 1, and 294.85 ± 8.33 mOsm/L (range: 283–311) in Group 2 (p = 0.03). In Group 1, tear osmolarity values were positively correlated with OSDI scores (r(18) = 0.55, r2 = 0.31, p = 0.01), DEWS classification grades (r(18) = 0.73, r2 = 0.54, p < 0.01), temporal and total corneal staining scores (r(18) = 0.67, r2 = 0.44, p < 0.01, and r(18) = 0.51, r2 = 0.26, p = 0.02, respectively), temporal conjunctival staining scores (r(18) = 58, r2 = 0.34, p < 0.01); and negatively correlated with anesthetized Schirmer test results (r(18) = -0.62, r2 = 0.38, p < 0.01) and TFBUT (r(18) = -0.50, r2 = 0.25, p = 0.02). Conclusions: Tear osmolarity values were found to be greater in patients with dry eye syndrome related to primary SS compared to control subjects, and positively correlated with the severity of dry eye.

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.

TRAF1/C5, eNOS, C1q, but not STAT4 and PTPN22 gene polymorphisms are associated with genetic susceptibility to systemic lupus erythematosus in Turkey

A significant source of variability in the literature on systemic lupus erythematosus (SLE) susceptibility genes has been the inability to replicate genetic findings across different racial or ethnic groups. We investigated whether a single nucleotide polymorphism (SNP) of the STAT4 (rs7574865), PTPN22 (rs2476601), TRAF1/C5 (rs10818488), and C1q (rs292001) genes as well as the 27-bp VNTR polymorphism on intron 4 of eNOS, previously associated with SLE in other populations, are also associated with SLE risk in Turkey. A group of 158 SLE patients and 155 healthy controls were included in this study. A genetic association of the TRAF1/C5, C1q, and eNOS gene polymorphism, but not of STAT4 and PTPN22, was found to confer a degree of risk for SLE. These data highlight the importance of comparative studies in different populations to confirm the previously detected genetic associations.

Identification of Susceptibility Loci in IL6, RPS9/LILRB3, and an Intergenic Locus on Chromosome 21q22 in Takayasu Arteritis in a Genome-Wide Association Study

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.

Genome-wide association study identifies susceptibility loci in IL6, RPS9/LILRB3, and an intergenic locus on chromosome 21q22 in Takayasu’s arteritis

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.

The Reliability and Validity of the Turkish Version of the Fibrofatigue Scale

ABSTRACT Objective: To validate translated Turkish version of the Fibrofatigue Scale [FFS]. Methods: The Turkish version of FFS was administered to a consecutive sample of 82 patients with fibromyalgia syndrome [FMS; 78 women]; mean age was 37 years and mean symptom duration was 2.3 years. The Turkish version of the Fibromyalgia Impact Questionnaire, the Beck Depression Inventory [BDI], and the Medical Outcome Survey Short Form-36 [SF-36] were documented. Reliability was tested by the test-to-test reliability [intraclass correlation coefficient] and internal consistency [Cronbachs alpha coefficients]. Construct validity was assessed by association with BDI and SF-36 [Spearmans correlation coefficient]. Paired t-test was used to determine the statistical significance of change score [responsiveness]. Results: The test–retest reliability and internal consistency of the FFS were excellent with intraclass correlation coefficient of 0.98 [0.97–0.99] and Cronbachs alpha of 0.74. The correlations between the FFS and the Fibromyalgia Impact Questionnaire items [rho = 0.56], BDI [rho = 0.52], and subscales of SF-36 [rho value ranging from −0.333 to −0.553] were adequate. The FFS score improved significantly after a four-week physical therapy program [P < 0.001]. Conclusions: The Turkish FFS is a reliable and valid instrument for detecting and measuring functional disability and symptom severity in Turkish patients with FMS.

Identification of Susceptibility Loci inIL6,RPS9/LILRB3, and an Intergenic Locus on Chromosome 21q22 in Takayasu Arteritis in a Genome-Wide Association Study: GENETIC SUSCEPTIBILITY LOCI IN TAKAYASU ARTERITIS

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.