Ömer Nuri Pamuk

We aimed to evaluate the relationship between some important genetic variations and expressions of these genes in our SLE population. We also determined their association with clinical parameters. Eighty-four SLE patients (79 F, 5 M) and 105 healthy controls (98 F, 7 M) were included in the study. rs13277113, rs2736340, rs7829816, rs6983130, rs2613310, and rs704853 polymorphisms, gene expressions of Src family kinases (Blk, Hck, Lck, and Lyn), and Syk kinases (Syk, ZAP70) were studied by real-time PCR. The heterozygous genotypic pattern (GA) for rs13277113 polymorphism was more frequent in patients with SLE when compared to that in controls (48.8 vs. 31.4%, p = 0.035). Other genotype variants were similar in SLE patients and controls. In the SLE group, the heterozygous genotype for rs13277113 was significantly less frequent in active SLE patients (58.8 vs. 26.7%, p = 0.01). SLE flares according to the SELENA-SLEDAI flare index were significantly more frequent in GA (rs13277113) (70 vs. 37%) and CT (rs2736340) genotypes (66.7 vs. 35.2%) than those in other genotypes (p values p values 0.01 and 0.017). We observed more frequent heterozygous GA genotypic pattern (rs13277113) in our SLE patients compared to that in controls; and it was associated with disease flares. Blk gene expression in SLE was lower, especially in relapsing patients.

Epidemiological data about antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is very limited. Until now, there has been no study about the epidemiology of AAV in Turkey. In this study, we evaluated the frequency of AAV in the northeastern part of Turkey. The general clinical features of patients diagnosed with AAV at our center within the last 10 years (2004–2014) were retrospectively recorded down. The incidence rates and the prevalence per 1,000,000 population aged ≥16 years were calculated. In addition, we evaluated the clinical features and survival rates of AAV patients. There were 30 patients with granulomatous polyangiitis (GPA), 15 with microscopic polyangiitis (MPA), and 5 with eosinophilic polyangiitis (EGPA). The overall prevalence of AAV in our region was 69.3/1,000,000 in individuals ≥16 years. Males had a similar prevalence (73.2/1,000,000) with females (65.4/1,000,000). The mean annual incidence rate was 8.1/million for all AAV. The annual incidence of AAV in females was 6.9/million; in males, it was 9.2/million. The annual incidence for GPA was calculated as 4.8/1,000,000, the incidence for MPA was 2.4/1,000,000, and the incidence for CSS was 0.8/1,000,000. Ten-year survival of patients with AAV was 65.3 %. The only independent poor prognostic factor in Cox’s multivariate analysis was advanced age at the time of diagnosis (OR 7.5, 95 % CI 10.6–526, p = 0.043). The frequency of all AAV in northwestern Turkey was similar to that in southern Europe; however, it was lower than the frequency in Northern Europe.

In our study, we compared the sensitivity and specificity of the new ACR/EULAR 2013 criteria to the ACR 1980 criteria in our systemic sclerosis (SSc) population. Three rheumatology centers from Turkey participated into this study. The medical records of SSc patients diagnosed between 2008 and 2014 were retrospectively reviewed, and their features at disease onset were recorded. Patients admitted to each center within the same time period for conditions other than SSc, in whom ANA was positive and was deemed necessary within the diagnostic workup, were included as controls. One hundred and ninety-seven SSc patients (174 females, 23 males) and 103 controls (96 females, 7 males) were included. Limited cutaneous SSc was present in 68 % of patients, and 30.5 % had diffuse SSc. The sensitivity of ACR/EULAR 2013 and ACR 1980 criteria were, respectively, 94.4 and 85.3 % (p = 0.003). The specificity of ACR/EULAR 2013 and ACR 1980 criteria were, respectively, 98.1 and 100 %. According to the new criteria, 13 patients were misclassified; however, according to the ACR 1980 criteria, 29 patients were misclassified (p = 0.005). The sensitivity of ACR/EULAR 2013 criteria was significantly better than that of the ACR 1980 criteria in limited cutaneous SSc group (94.8 vs. 82.8 %). In patients whose disease duration was <3 years, the new criteria had better sensitivity than the previous criteria (92.7 vs. 78.1 %, p = 0.006). The new ACR/EULAR 2013 criteria for SSc had better sensitivity in Turkish SSc patients, and less patients were misclassified.

Genetic polymorphisms of platelet endothelial cell adhesion molecule-1 (PECAM-1) were found to play roles in atherosclerotic events. We determined PECAM-1 polymorphisms, soluble PECAM-1, and CD40L levels in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and evaluated their associations with clinical atherosclerotic complications. We included 100 RA patients, 81 SLE patients, and 94 healthy controls. The clinical features about the patients were obtained from medical records. Past cardiovascular complications were recorded. The most frequent gene polymorphisms of PECAM-1 were studied in our genetics laboratory. Soluble PECAM-1 and CD40L levels in serum were determined with ELISA. The frequencies of 373C (rs668) and 1688A (rs12953) alleles were higher in RA patients when compared to controls (p values, 0.028 and 0.016). RA and SLE patients had significantly higher allele frequencies for 2008A (rs1131012) when compared to controls (p values, 0.016 and 0.001). SLE patients had significantly more frequent AA genotype for rs1131012 polymorphism than RA patients and controls (p values, 0.007 and p values p = 0.021). SLE patients with CC genotype (rs668) had a significantly lower frequency of atherosclerotic complications than those with CG genotype (p = 0.045). Nevertheless, in multivariate analysis, there was no association between genotype and atherosclerotic complications. We found associations between various PECAM-1 polymorphisms in RA and SLE; PECAM-1 and soluble CD40 ligand (sCD40L) levels were significantly higher in RA patients than in SLE and control groups. PECAM-1 polymorphisms in SLE were protective against atherosclerotic complications.

Objectives: We evaluated the frequency of clinical apparent amyloid deposition, clinical features and outcome in our rheumatoid arthritis (RA) patients. Methods: Medical records of 1415 RA patients were examined. During routine follow-up, RA patients with proteinuria on urinalysis, underwent rectal biopsy. Results: Eleven patients (0.78%) were diagnosed with clinical apparent amyloid deposition. While the mean annual incidence of AA amyloidosis between 2001 and 2005 was 0.2%, it was 0.13% between 2006 and 2011. At initial presentation, three RA-related AA amyloidosis patients had nephrotic-range proteinuria and renal insufficiency, four had only nephrotic-range proteinuria, three had non-nephrotic-range proteinuria, and one had non-nephrotic-range proteinuria and renal insufficiency. The mean age in RA patients with AA amyloidosis was 60.8 years and disease duration was 12 years. Ten of 11 cases had positive rheumatoid factor. Two RA patients with AA amyloidosis who had been diagnosed in the pre-anti-TNF era died. Of the rest nine patients with AA amyloidosis, eight were administered anti-TNF therapy and one was given rituximab. In four patients, anti-TNF therapy led to disappearance of clinical features, decrement in proteinuria and resulted in improvement of or at least stabilization of renal functions. One patient using anti-TNF therapy died because of tuberculosis. One patient discontinued anti-TNF therapy and developed end-stage renal disease. Two patients have been started to be given anti-TNF therapy recently. In one patient who was given rituximab, there was regression of proteinuria and improvement in renal functions. Conclusions: We diagnosed a 0.78% frequency of AA amyloidosis in RA. It seems that – other than the risks of infection, tuberculosis – anti-TNF drugs seem to be effective on RA disease activity and also have renoprotective effects in RA patients with AA amyloidosis.

In this study, we aimed to evaluate the relation between angiogenesis indicators and T helper 17 cytokine group in patients with systemic sclerosis (SSc) which is a disease characterized by impaired angiogenesis and autoimmune response. In our study, patients with SSc are compared with patients with primary Raynaud’s phenomenon (RP) and healthy controls. Forty SSc patients, 18 primary RP cases, and 20 healthy controls were included in our study. The demographic and clinical features of patients with SSc were recorded. The serum levels of vascular endothelial growth factor (VEGF), vascular endothelial (VE)-cadherin, interleukin (IL)-20, IL-22, and IL-23 were assessed. In the SSc group, IL-20 level was significantly lower than in both primary RP group and controls (p values 0.05). In SSc patients, IL-23 correlated negatively with VEGF (r = −0.36, p = 0.025) and positively with VE-cadherin (r = 0.55, p < 0.001). IL-20 levels in SSc patients correlated with disease duration (r = 0.32, p = 0.044). SSc patients with limited involvement had significantly higher VE-cadherin levels than SSc patients with diffuse involvement (p = 0.044). We observed that IL-20 which is an IL-10 group angiogenesis indicator was observed to be suppressed in SSc, suggesting abnormal angiogenesis.

We evaluated the roles of sociocultural status, distress and cognitive functions in rheumatoid arthritis (RA) patients who developed methotrexate (MTX)-related neutropenia. The data of 37 RA patients with MTX-related neutropenia who were being followed up at 3 centers were evaluated. The control group included 74 RA patients. The clinical features, biochemical tests and treatment modalities of the patients were obtained from hospital files. The mini-mental state examination (MMSE) test and the Hospital Anxiety and Depression Scale (HADS) were administered for all RA patients with neutropenia as well as the control group. The frequencies of male patients, illiterate patients, patients living alone, patients with serious visual impairment, those with low income, and patients with high creatinine were significantly higher among RA patients with MTX-related neutropenia than in controls (p values p values p < 0.001). Twenty-six of the 37 patients (70.3 %) developed neutropenia with daily dosing. Patients who used MTX daily were more likely to be living alone than those using weekly dosing (p = 0.011). Multivariate analysis showed that having probable dementia on the MMSE test (OR 52.6), low income level (OR 56.8) and age (OR 1.12) were independent risk factors for the development of MTX-related neutropenia. The presence of probable dementia on MMSE, low socioeconomical status and older age are associated with serious toxicity in RA patients using MTX. Measures should be taken to prevent wrong MTX dosing by the patients. Compliance and patient education is of major importance, in particular, in the patients presented in this study.

We evaluated the frequency of secondary amyloidosis, associated clinical features, and outcomes in ankylosing spondylitis (AS) patients diagnosed in the last decade. The medical records of AS patients diagnosed at single academic medical center were reviewed for clinical evidence of amyloidosis. During routine follow-up, routine urinalysis was performed at each visit; patients with significant proteinuria underwent rectal biopsy. We diagnosed 8 clinically apparent amyloidosis patients (1.1 %) in our cohort of 730 AS patients (508 males, 222 females). Four patients undergoing hemodialysis were diagnosed secondary amyloidosis. Three patients had nephrotic syndrome and renal dysfunction and one patient had non-nephrotic proteinuria. When AS patients with amyloidosis were compared to AS controls, it was observed that the amyloidosis group was older, had longer disease duration, higher initial BASDAI scores, and ESR values, and more frequent peripheral arthritis (p < 0.05). Logistic regression analysis revealed that the initial BASDAI level was an independent predictor for the development of secondary amyloidosis (OR:2.36). Six patients were administered anti-TNF therapy. The clinical findings resolved in these. In 2 patients with nephrotic syndrome and renal dysfunction, in addition to clinical improvement, there was a decrement in proteinuria; renal function improved or remained stable. Anti-TNF therapy is safe and effective in patients with renal failure, and at an earlier stage, appears effective in improving renal function. The development of proteinuria in AS patients should occasion a search for underlying amyloidosis.

We evaluated the incidence of subclinical atherosclerosis and associated factors in our gouty arthritis patients. We included 55 gouty arthritis patients diagnosed at our center within the last 4 years. The control group included 41 patients with rheumatoid arthritis (RA) and 34 patients with asymptomatic hyperuricemia (AHU). Atherosclerotic risk factors were determined in all subjects. Carotid intima-media thickness (IMT) and the presence of plaques were evaluated by B-mode ultrasonography. The carotid IMT in gouty arthritis patients (0.730 ± 0.19) was significantly higher than in AHU subjects (0.616 ± 0.12) (P = 0.004) and tended to be higher than the RA group (0.669 ± 0.17) (P = 0.1). Atheromatous plaques were significantly more frequent in gouty arthritis patients (16 cases, 29.1%) than in RA patients (5 cases, 12.2%) and AHU subjects (3 cases, 8.8%) (P values, 0.05 and 0.023). Gout patients with plaques were older (P = 0.006) and tended to have tophi more frequently (P = 0.06). Logistic regression analysis showed that age (OR: 1.3, 95% CI: 1.02–1.54) and the presence of tophi (OR: 12.5, 95% CI: 1.2–140) were independent risk factors for the presence of plaques. Gouty arthritis bears a higher risk of atherosclerosis than both RA and AHU.