Rituximab therapy in pericarditis associated with rheumatoid arthritis.

In rheumatoid arthritis, pericarditis is commonly asymptomatic, but rarely, it progresses to a morbid complication, like cardiac tamponade or restrictive pericarditis. Current studies have indicated that conventional drugs have limited ability to reverse these lethal conditions. To date, invasive surgical measures remain the only definitive therapy for patients who are unresponsive to drugs. Recently, anti-tumor necrosis factor-α and anti-interleukin-1 antibody-based drugs have shown limited success. Consequently, given the importance of pericarditis, we need new treatment methods. Here, we describe a patient with rheumatoid arthritis and effusive pericarditis, which progressed to life-threatening cardiac tamponade. The patient responded very well to rituximab. Thus, rituximab represents a potential new therapy for this rarely treated complication of rheumatoid arthritis.

Glomerulonephritis and Coombs-positive hemolytic anemia mimicking scleroderma renal crisis in an overlap of systemic lupus erythematosus and diffuse systemic sclerosis.

Systemic sclerosis (SSc) may overlap frequently with other rheumatic diseases, including systemic lupus erythematosus (SLE), which can require high-dose steroids depending on the clinical presentation. We present a case involving this overlap in which the patient concomitantly developed lupus nephritis and Coombs (+) hemolytic anemia, which was confused with scleroderma renal crisis. In this condition, assessing for lupus nephritis with timely renal biopsy and lupus serology can aid in guiding the appropriate treatment. We discuss the clinical features and challenging management of this case with a review of the English-language literature for SSc and SLE overlap with glomerulonephritis.

Osteoprotegrin interacts with biomarkers and cytokines that have roles in osteoporosis, skin fibrosis, and vasculopathy in systemic sclerosis: A potential multifaceted relationship between OPG/RANKL/TRAIL and Wnt inhibitors.

Objectives: We explored the interactions of osteoprotegerin (OPG) with biomarkers of bone turnover and cytokines, including soluble receptor activator for nuclear factor kappa beta ligand (sRANKL), tumor necrosis factor-related apoptosis-induced ligand (TRAIL), and Wnt inhibitors in osteoporosis, vasculopathy and fibrosis related to systemic sclerosis (SSc). Methods: The study included 46 SSc patients and 30 healthy controls. Skin thickness, pulmonary fibrosis and/or hypertension, digital ulcers, and calcinosis cutis of SSc patients were assessed. We determined bone mineral density (BMD), and OPG, sRANKL, TRAIL, secreted frizzled-related protein 1 (sFRP-1), Dickkopf-related protein 1 (DKK-1), sclerostin in the serum of both patients and controls. Results: OPG, sclerostin, and sFRP-1 levels were similar between patients and controls (P > 0.05). Femoral neck and lumbar spine BMD and vitamin D levels were lower, and the OC, NTX, sRANKL, DKK1 and TRAIL levels were significantly higher, in patients than in controls (p < 0.05). In subgroup analysis, patients with higher modified Rodnan skin score (mRodnan) had higher DKK-1, sclerostin, and TRAIL levels (p < 0.05); those with diffuse SSc subtype had lower BMD values than those with limited SSc (p < 0.05). Skin and pulmonary fibrosis linked negatively with BMD measures. Conclusion: we showed that sRANKL levels were higher and correlated with bone turnover markers. It may be related to osteoporosis in SSc. The OPG level was unaltered in SSc patients. Higher TRAIL levels associated with skin thickness may indicate vascular dysfunction or injury. Higher DKK-1 and sclerostin levels may be related to a reactive increase in cells and be prominently linked to fibrosis in SSc.

Parenchymal neuro-Behçet disease with erectile dysfunction and micturition disturbances: case report and literature review.

Parenchymal neuro-Behçet disease (NBD) is a serious clinic condition with a sub-acute or chronic disease course that results in incapability through pyramidal tract involvement. Though well-known consequences can deter a patient's life, both urinary symptoms and sexual dysfunction are underestimated complications of NBD and closely related in timing. Here, we report the case of a young male patient with parenchymal NBD who developed urinary incontinence and erectile dysfunction in addition to widespread pyramidal tract signs and symptoms. We discuss clinical features, prognosis and treatment of the case. A review of English literature was conducted for cases of concurrent urinary or sexual dysfunction complicating parenchymal-NBD.

Epidemiology of Takayasu's arteritis in Turkey.

OBJECTIVES: To estimate the prevalence and incidence of Takayasu arteritis (TA) among the residents of the city of Izmir, the third largest metropolis in Turkey. METHODS: Five tertiary care teaching hospitals, which were the only ones that provided rheumatology specialty care during the study period in the city of Izmir from 2006 through 2010, were invited to take part in the present study. A case search was performed electronically in the information systems of these hospitals using The International Classification of Diseases Tenth Revision (ICD-10) code for Takayasu arteritis (M31.4). The diagnosis was confirmed through chart review by a rheumatologist according to the 1990 American College of Rheumatology (ACR) criteria. Annual prevalence was calculated based on the number of patients that were alive at the end of 2010. Age- and sex-adjusted prevalence rates were standardised according to the 2010 Turkish population, based on 2010 Turkish Census. RESULTS: A total of 41 patients were confirmed to have TA and also to live within the targeted area. The annual prevalence was estimated as 12.8 (95% CI 12.0-13.6) per million; 23.5/million (95% CI 21.9-25.0) in females and 1.9/million (95% CI 1.5-2.4) in males. The prevalence was higher 8.8/million (95% CI 7.7-10.0) in the population >40 years of age. During the study period, the mean annual incidence of TA was estimated as 1.11/million (95% CI 0.54-1.67). CONCLUSIONS: The first epidemiologic study of TA in a Turkish population suggests that TA is a relatively common vasculitis in Turkey.

Bilateral orbital pseudotumor in a patient with Takayasu arteritis: a case report and review of the literature.

Inflammatory orbital pseudotumor is often associated with rheumatologic disorders. It has been reported commonly with ANCA-associated vasculitides, especially granulomatosis with polyangiitis (Wegener's granulomatosis). There are also a few cases of large vessel vasculitis such as giant cell arteritis and Behcet's disease. Here, we report a patient with undiagnosed Takayasu arteritis presenting with proptosis and diplopia, with later diagnosis of an inflammatory pseudotumor of the orbit. In this case, we believe extensive involvement of blood vessels, including bilateral pulmonary artery stenosis, and elevated inflammatory markers that show disease activity may be related to pseudotumor formation in Takayasu arteritis. Since this is an unusual and unreported presentation of the disease, better estimation of a causal relationship may be possible in the future with further information. In conclusion, although uncommon, this case highlights that orbital pseudotumor may be an important finding in Takayasu arteritis. For early diagnosis, better treatment, and good prognosis, it should be considered in patients presenting with ocular symptoms similar to the other vasculitides.

S1000A12, Chitotriosidase, and Resolvin D1 as Potential Biomarkers of Familial Mediterranean Fever.

Familial Mediterranean fever (FMF) is an auto-inflammatory disease characterised by periodic inflammatory attacks. We investigated changes in monocyte-granulocyte derived S10012A and chitotriosidase in both the attack and silent period of FMF for better estimation of inflammation. Endogenous resolvin was determined for utility to restrict inflammation. This study included 29 FMF patients (15 M/14 F) and 30 healthy controls (15 M/15 F). Serum levels of highly sensitive C-reactive protein, serum amiloid A (SAA), S100A12, chitotriosidase, and resolvin D1 were measured. Age, sex, body mass indexes, and lipids were similar between patients and controls. Biomarkers including hs-CRP, SAA, S100A12, chitotriosidase, and resolvin D1 were higher in the attack period of FMF patients compared to controls (P < 0.001). When FMF patients in the silent period were compared with their attack period, hs-CRP, SAA, and chitotriosidase were found elevated in the attack period (P < 0.001, P < 0.001, and P = 0.02 respectively). Serum levels of SAA, S100A12, chitotriosidase, and resolvin D1 in the silent period of FMF patients were still found elevated compared to healthy controls, indicating subclinical inflammation (P < 0.001, P < 0.001, P = 0.009, and P < 0.001 respectively ). In subgroup analysis, patients with M694V homozygote and heterozygote mutations had higher S10012A and hs-CRP compared to other mutation carriers. Our findings indicate that chitotriosidase and S10012A are useful in diagnosis and detection of subclinical inflammation and/or assessment of disease activity in FMF patients. They could be more informative for inflammation in various disease states compared to hsCRP and SAA. Resolvin D1 is elevated in both the attack and silent periods of FMF. It may be helpful to restrict inflammation.

Vasculitis and long standing ankylosing spondylitis in a patient with familial Mediterranean fever.

Coexistence of familial Mediterranean fever (FMF) and other inflammatory disorders has been frequently reported, but no specific underlying factor has been identified. We report a patient with FMF who is presented with long-standing ankylosing spondylitis (AS) and cutaneous leukocytoklastic vasculitis (LV) of the lower limbs. It is the first report on combination of FMF with AS and LV. The Mediterranean Fever (MEFV) gene mutation of heterozygote (R202Q/R726A) and HLA-B27 are detected in this case, and are believed to form genetic susceptibility to LV.

The cost of care of rheumatoid arthritis and ankylosing spondylitis patients in tertiary care rheumatology units in Turkey.

OBJECTIVES: To determine the direct and indirect costs due to rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients in Turkey. METHODS: An expert panel was convened to estimate the direct and indirect costs of care of patients with RA and AS in Turkey. The panel was composed of 22 experts chosen from all national tertiary care rheumatology units (n=53). To calculate direct costs, the medical management of RA and AS patients was estimated using 'cost-of-illness' methodology. To measure indirect costs, the number of days of sick leave, the extent of disability, and the levels of early retirement and early death were also evaluated. Lost productivity costs were calculated using the 'human capital approach', based on the minimum wage. RESULTS: The total annual direct costs were 2,917.03 Euros per RA patient and 3,565.9 Euros for each AS patient. The direct costs were thus substantial, but the indirect costs were much higher because of extensive morbidity and mortality rates. The total annual indirect costs were 7,058.99 Euros per RA patient and 6,989.81 for each AS patient. Thus, the total cost for each RA patient was 9,976.01 Euros and that for an AS patient 10,555.72 Euros, in Turkey. CONCLUSIONS: From the societal perspective, both RA and AS have become burden in Turkey. The cost of lost productivity is higher than the medical cost. Another important conclusion is that indirect costs constitute 70% and 66% of total costs in patients with RA and AS, respectively.

Evaluation of the T helper 17 axis in ankylosing spondylitis.

To evaluate the T helper 17 (Th17) axis and its relation to tumor necrosis factor (TNF) alpha blockage and disease activity in ankylosing spondylitis (AS). The study included 127 AS patients (100M/27F) and 38 (27M/11F) controls. Spinal mobility was assessed by the bath ankylosing spondylitis metrology index (BASMI). Patients were also evaluated with the bath ankylosing spondylitis functional (BASFI) and bath ankylosing spondylitis disease activity index. Cytokines including IL-6, IL-12, TGF-ß, IL-17A, and IL-23 were measured in serum sample using commercially available ELISA kits. Cytokines including IL-6, IL-12, TGF-ß, IL-17, and IL-23 were significantly higher in the AS patients than the controls (P < 0.05). The Th-17-related cytokines were not different between patients treated with anti-TNF and conventional therapies (P > 0.05). Cytokines were also similar between patients with active and inactive disease (P > 0.05). On correlation analysis, IL-17 was correlated with IL-23 and IL-12 (P < 0.05) and IL-23 showed correlations with IL-12 and BASMI (P < 0.05). We found serum levels of Th-17-related cytokines to be significantly increased in the sera of AS patients. Disease activity and treatment type did not affect the level of these cytokines.

Biomarkers and cytokines of bone turnover: extensive evaluation in a cohort of patients with ankylosing spondylitis.

BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory disease of spine and sacroiliac joints; it is characterized by new bone formation, and the disease processes can be accompanied by osteoporosis. In the present study, we investigated changes in bone mineral density (BMD) and in the levels of various bone turnover-related biomarkers and cytokines in a cohort of AS patients, with regard to clinical parameters, disease activity, and treatment regimen. METHODS: 55 AS patients and 33 healthy controls included in the study. Spinal mobility was assessed by the Bath Ankylosing Spondylitis Metrology Index (BASMI), and radiologic changes were scored by the Bath Ankylosing Spondylitis Radiologic Index (BASRI). Patients were also evaluated with the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Bone mineral density (BMD) assessed by dual energy X-ray absorptiometry. Various biomarkers and cytokines of bone turnover including osteoprotegerin (OPG), serum band 5 tartrate-resistant acid phosphatase (TRAP-5), soluble receptor activator of nuclear factor kappa-B ligand (sRANKL), secreted frizzled-related protein 1 (sFRP-1), Dickkopf-related protein 1 (DKK-1), and sclerostin were studied. RESULTS: The levels of TRAP-5, NTX, sRANKL, sclerostin, sFRP-1, DKK-1, and IFNγ, were similar between the patients and controls (p > 0.05), while BMD of femoral neck, and OPG levels were significantly lower in AS patients (p < 0.05). In a subgroup analysis, patients with active disease had significantly higher concentrations of OPG compared with the inactive group. Rest of the biomarkers and cytokines of bone turnover were similar between the active and inactive disease groups. Subgroup analysis of patients receiving anti-TNFα agents and conventional therapy revealed that OPG concentrations were significantly lower in the patients receiving biological drugs, while BAP and DKK-1 were significantly higher in the patients treated with conventional agents. CONCLUSIONS: In this cross-sectional study we showed that OPG levels were significantly lower in AS patients compared to healthy subjects. On the other hand, the levels of wingless (Wnt) signal pathway inhibitors seem not altered. Ectopic bone formation in AS may be related to dysfunction of these molecules at the cellular level.

Serum neudesin levels in patients with polycystic ovary syndrome.

OBJECTIVES: We aimed to investigate serum neudesin levels that has neural, metabolic functions in patients with polycystic ovary syndrome (PCOS). MATERIAL AND METHODS: The study included 180 women (age range, 18-44 years) with a diagnosis of PCOS and a control group that included 100 healthy females (age range, 18-46 years). Body mass index (BMI), waist circumference, Ferriman-Gallwey score, was evaluated and plasma glucose, lipid profile, estradiol, progesterone, total testosterone, prolactin, insulin, dehydroepiandrosterone sulfate (DHEA-S), FSH, LH, free T3, free T4, thyroid stymulating hormone (TSH), anti-thyroperoxidase (anti-TPO) antibody and neudesin levels were evaluated in all participants. RESULTS: BMI and waist circumference were similar between two groups. Ferriman-Gallwey score was significantly higher in the patient group. Fasting blood glucose, HbA1C, lipid parameters except triglyceride levels, free T3, free T4, TSH, anti-TPO were similar between the two groups. Triglyceride, insulin and HOMA values were significantly higher in PCOS patients. While follicle-stimulating hormone (FSH), estradiol, progesterone, prolactin and DHEAS levels were similar, LH was significantly higher in patients with PCOS. Serum neudesin level was significantly lower in PCOS patients with respect to controls (p = 0.015). Neudesin was positively correlated with insulin (r = 0.224, p = 0.037), and progesterone (r = 0.716, p = 0.001). Multiple regression analysis revealed that neudesin correlated with only progesterone (beta = 0.308, p = 0.001). CONCLUSIONS: Due to the association of decreased levels of neudesin with PCOS and correlation of neudesin with progesterone, neudesin may be related with one of patophysiologic pathways of PCOS. Still, it is not certain that decreased neudesin is involved in the pathogenesis of PCOS or is the result of the disorder.

Association of Leptin Levels and Disease Activity in Patients with Early Rheumatoid Arthritis.

OBJECTIVE: Previous studies have reported a link between metabolic parameters and disease activity in rheumatoid arthritis (RA), although the evidence is limited in early RA. We aimed to investigate the relationship between disease activity and adipocytokine levels in subjects with early RA. METHODS: Forty-seven patients with early RA (symptom duration ≤12 months) were enrolled. Disease activity was determined by DAS28-CRP. Patients were treated with DMARDs according to the EULAR recommendations. Subjects were tested before and five months after treatment. RESULTS: Early RA patients with high disease activity (DAS28-CRP > 4.9) had greater BMI (31.2 ± 6.8 kg/m2 vs. 26.7 ± 4.1 kg/m2; p = 0.006) and higher leptin levels (14.62 ± 15.60 ng/mL vs. 7.82 ± 8.00 ng/mL; p = 0.048). Levels of other adipocytokines were not significantly different. Leptin levels were similar in subjects with mild/moderate disease activity and controls. DAS28-CRP was correlated with leptin (r = 0.303, p = 0.039). Leptin levels decreased significantly after treatment (from 10.86 ± 12.34 ng/mL to 9.22 ± 9.29 ng/mL; p = 0.047) along with insulin levels (from 13.68 ± 21.90 mU/L to 7.09 ± 4.72 mU/L; p = 0.010) and HOMA-IR (from 4.39 ± 9.53 to 1.70 ± 1.38; p = 0.012). HDL cholesterol levels increased (from 41 ± 10 mg/dL48 ± 10 mg/dL; p <0.001). CONCLUSION: Leptin levels were associated with disease activity in patients with early RA and these levels decreased after treatment with DMARDs. Further research is needed to elicit leptin's role to regulate disease activity in early RA.

Efficacy of SLZ and MTX (alone or combination) on the treatment of active sacroiliitis in early AS.

Sacroiliitis is an important sign of spondylarthritis (SpA) of which the prototype disease is ankylosing spondylitis. The radiographic changes required for diagnosing AS occur as late as 8-11 years after the onset of clinical symptoms. Nonsteroid anti-inflammatory drugs (NSAIDs) have been the main treatment for spondylitis of AS. For patients refractory or intolerant to NSAIDs, disease-modifying antirheumatic drugs (DMARDs) have been used as a second-line approach. Sulphasalazine (SLZ) is known as the best DMARD in treatment of peripheral arthritis; also methotrexate (MTX) is currently one of the most widely used DMARDs. But there was no objective information about inflammation of sacroiliac joints during treatment with these DMARDS that are the first places of the beginning point of SpA. For this purpose, in this study, the effect of SLZ and MTX, which are used alone and combination in 6 months, on treatment of active sacroiliitis, which is shown by dynamic magnetic resonance and acute phase reactants in laboratory has been investigated. 55 patients (F:M = 34:21) with active sacroiliitis [mean age = 37.05 + 13.03 year (n = 55)] were evaluated and determined by dynamic magnetic resonance imaging in this study. The better response in the SLZ treatment group than the other two groups has been obtained. Nevertheless, those changes were not statistically found different. In conclusion, the ratio of treatment of active sacroiliitis, especially early period, with SLZ as a DMARD is better than MTX or MTX + SLZ, but this difference is not statistically significant. A prospective study of the treatment of active sacroiliitis by DMARDs may be more illustrative.

Oxidative stress and related factors in patients with ankylosing spondylitis.

OBJECTIVE: Ankylosing spondylitis (AS) is a chronic inflammatory disease of the spine and sacroiliac joints of unknown etiology. Recent studies have reported increased oxidative stress, which is implicated in the pathogenesis of a number of diseases, in AS. The purpose of this study was to investigate oxidative stress and related factors in AS. MATERIAL AND METHODS: Eighty-five patients with AS [36 (16-64) years; 65 male/20 female] and 56 healthy subjects [36 (21-63) years; 39 male/17 female] with no known cardiovascular risk factors were enrolled. Serum total oxidant status (TOS) and total anti-oxidant status (TAS) were studied. The Bath ankylosing spondylitis functional index (BASFI), Bath ankylosing spondylitis disease activity index (BASDAI), and Bath ankylosing spondylitis metrology index (BASMI) were calculated. A logistic regression model was used to identify the independent risk factors for TOS. RESULTS: No differences were observed in terms of demographic characteristics, laboratory findings, or TAS concentrations between the patient and control groups. However, the serum TOS levels were significantly higher in the AS group than in the controls (p=0.003). The comparison of cases of active (BASDAI ≥4) and inactive AS revealed significantly higher TOS levels in the active disease group. The TOS and TAS concentrations did not differ between patients treated with biological agents and those treated with conventional agents. Correlation analysis yielded significant correlations between TOS and TAS, BASMI, BASFI, BASDAI, erythrocyte sedimentation rate (ESR), and high-sensitive C-reactive protein (hs-CRP) (p<0.05; r values ranged from 0.291 to 0.452) and a positive correlation between TAS and BASMI (p<0.05; r=0.344). Based on regression analysis, BASDAI, BASMI, and hs-CRP independently predicted the TOS levels [p<0.05, R2: 0.262, and standard error of the estimate (SEE): 10.96]. CONCLUSION: Oxidative stress levels were higher in patients with AS than in healthy subjects. Patients with active disease status had significantly higher oxidative stress than patients with inactive disease status and healthy controls. Treatment status has no effect on TOS, and BASMI, BASDAI, and hs-CRP are independent variables associated with TOS. The TAS levels were found to be associated with only BASMI.

Is there a relationship between endothelial nitric oxide synthase gene polymorphisms and ankylosing spondylitis?

OBJECTIVE: Nitric oxide is produced by endothelial nitric oxide synthase, and its production can be influenced by polymorphisms of the endothelial nitric oxide synthase gene. Because candidate genes responsible for susceptibility to ankylosing spondylitis are mostly unknown and available data suggest that there may be problems related to the nitric oxide pathway, such as endothelial dysfunction and increased asymmetric dimethylarginine, this study aimed to assess the association of common endothelial nitric oxide synthase gene polymorphisms with ankylosing spondylitis. METHODS: One hundred ninety-four unrelated Turkish ankylosing spondylitis patients and 113 healthy without apparent cardiovascular disease, hypertension or diabetes mellitus were included. All individuals were genotyped by PCR-RFLP for two single-nucleotide polymorphisms, namely 786T>C (rs2070744, promoter region) and 786 Glu298Asp (rs1799983, exon 7). Variable numbers of tandem repeat polymorphisms in intron 4 were also studied and investigated by direct electrophoresis on agarose gel following polymerase chain reaction analysis. The Bath ankylosing spondylitis metrology index of the patients was calculated, and human leukocyte antigen B27 was studied. RESULTS: All studied polymorphisms satisfied Hardy-Weinberg equilibrium. Sex distributions were similar between the patient and control groups. No significant differences were found in the distributions of allele and genotype frequencies of the studied endothelial nitric oxide synthase polymorphisms between patients and controls. There were no correlations between endothelial nitric oxide synthase polymorphisms, disease duration, Bath ankylosing spondylitis metrology index or human leukocyte antigen B27. CONCLUSION: The results presented in this study do not support a major role of common endothelial nitric oxide synthase polymorphisms in Turkish ankylosing spondylitis patients.

Evaluation of various endothelial biomarkers in ankylosing spondylitis.

Atherosclerosis has been shown to be increased in chronic inflammatory diseases including ankylosing spondylitis (AS). Impaired endothelial function, the first step in atherosclerosis, may be reflected by changes in various endothelial biomarkers of hemostasis and the release of several cellular adhesion molecules or cytokines. In this study, we investigated changes in the levels of various possible markers with regard to disease activity and treatment regimen with/without anti-TNF-α drugs. Fifty-six AS patients (44 males) and 27 controls (19 males) with no known cardiovascular risk factors were included in the study. Spinal mobility was assessed by the Bath Ankylosing Spondylitis Metrology Index, and patients were evaluated with the Bath Ankylosing Spondylitis Functional Index and the Bath Ankylosing Spondylitis Disease Activity Index. Cytokines and various endothelial biomarkers were measured in serum samples using commercially available ELISA kits. Age, sex, BMI, waist circumference, fasting glucose, MAP, lipids are all similar between patients and controls. von Willebrand factor (vWF), soluble thrombomodulin (sTM), and urotensin (UT-II) were found to be significantly higher in the sera of the patients compared to the controls. Treatment with anti-TNF-α compared to conventional therapy and disease activity in AS patients seemed to have no effect on the blood levels of UT-II, sTM, CD146, vWF, plasminogen activator inhibitor-1, tissue plasminogen activator, or the thrombin-antithrombin complex. The increased UT-II, sTM, and vWF in AS patient sera regardless of treatment and disease activity suggest an increased tendency for atherosclerosis.

Evaluation of circulating endothelial and platelet microparticles in men with ankylosing spondylitis.

OBJECTIVE: To evaluate the profiles of endothelial microparticles (EMP) and platelet microparticles (PMP) in men with ankylosing spondylitis (AS) and healthy subjects. We also aimed to determine whether microparticles (MP) correlate with disease activity, function, and spinal mobility indices. METHODS: There were 82 men with AS and 53 healthy controls. Subjects with a history of chronic diseases including coronary artery disease, hypertension, diabetes mellitus, and dyslipidemia were excluded. MP were stained with monoclonal antibodies against platelets and endothelial cells and quantified using flow cytometry. MP that were positive for both CD42a+/CD31+ and total CD42a+ were identified as PMP; and MP consisting of CD42a-/CD31+ and total CD144+ were considered EMP. RESULTS: EMP and PMP were similar between the patient and control groups (p > 0.05). Comparison of patients with AS in the active disease state (BASDAI ≥ 4) and in the inactive state showed that EMP and PMP were not different between the groups (p > 0.05). Correlation analysis revealed no correlation with Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, or Bath Ankylosing Spondylitis Metrology Index. C-reactive protein was significantly correlated with PMP and CD42a-/CD31+ EMP (p < 0.05). Comparison of patients with AS treated with anti-tumor necrosis factor (anti-TNF) drugs, subjects treated conventionally, and healthy controls revealed that PMP and CD42a-/CD31+ EMP were significantly downregulated in patients receiving biological agents. CONCLUSION: Circulating EMP and PMP, known to be indicators and mediators of vascular injury, were not significantly altered in men with AS who did not have classical cardiovascular risk factors. Significantly downregulated MP in patients receiving biological agents suggested that anti-TNF treatment may have a beneficial effect on vascular function in AS.

Fetuin-A and interleukin-18 levels in ankylosing spondylitis.

AIM: Interleukin-18 (IL-18) and fetuin-A have been implicated in atherosclerosis. Preliminary evidence suggests that ankylosing spondylitis (AS) is associated with an increased risk of atherosclerosis. The aim of the present study was to investigate possible abnormalities in IL-18 and fetuin-A levels in AS. METHODS: Subjects without established cardiovascular (CV) risk factors were studied. Fasting glucose, serum lipids, high sensitive C-reactive protein (hsCRP), erythrocyte sedimentation rate, IL-18 and fetuin-A were assessed. Patients were also evaluated with the Bath Ankylosing Spondylitis Metrology Index, Bath Ankylosing Spondylitis Functional Index, and the Bath Ankylosing Spondylitis Disease Activity Index. RESULTS: Fourty-five patients with AS (37.4 +/- 9.7 years; 35M/10F) and 29 controls (35.5 +/- 11.1 years; 21M/8F) were studied. Fetuin-A levels were significantly higher in AS patients compared to controls (1023.5 +/- 171.6 vs. 856.9 +/- 207.9 microg/mL, P < 0.001). IL-18 levels were also higher in the AS group but the difference was not significant (184 +/- 186 vs. 140 +/- 115, P = 0.1). Significant but weak correlations were found between fetuin-A, IL-18, hsCRP, low density lipoprotein cholesterol, and triglyceride levels (P < 0.05; r = 0.4, 0.3, 0.2, and 0.3 respectively). Comparison of subjects with respect to the treatment type, disease activity and history of peripheral arthritis yielded no difference regarding fetuin-A and IL-18 between groups. CONCLUSION: Fetuin-A and IL-18 levels seem to be increased in AS patients regardless of disease activity and treatment type.

Increased levels of asymmetric dimethylarginine (ADMA) in patients with ankylosing spondylitis.

OBJECTIVE: Endothelial dysfunction is present in ankylosing spondylitis (AS). However, the etiology of events is still unclear. The aim of the present study was to investigate whether there are abnormalities in nitric oxide (NO) metabolism and endothelin-1 (ET-1) in AS patients. METHODS: Subjects without any classical cardiovascular (CV) risk factors were studied. Fasting glucose, serum lipids, high sensitive CRP (hsCRP), ESR, asymmetric dimethylarginine (ADMA) and ET-1 were studied. Patients were also evaluated with the Bath Ankylosing Spondylitis Metrology Index, Bath Ankylosing Spondylitis Functional Index, and the Bath Ankylosing Spondylitis Disease Activity Index. RESULTS: A total of 48 AS patients (38.6+/-10.6 years; 36M/12F) and 38 controls (36.4+/-11.1 years; 27M/11F) were studied. Acute phase reactants including hsCRP, and ESR were significantly increased in the patients group (p<0.05). Serum ADMA concentrations were also significantly higher in AS than in controls. Plasma levels of ET-1 did not differ between the groups (p>0.05). Comparison of three groups (conventional and anti-TNF treatment groups and controls) revealed that ADMA was significantly higher in the conventional treated AS than in controls. The levels of ADMA were not different between anti-TNF group and healthy subjects. Plasma ET-1 concentrations were similar between groups (p>0.05). Correlation analysis yielded significant correlations between ADMA, hsCRP, LDL cholesterol, HDL cholesterol and triglycerides (p<0.05). CONCLUSION: The increased ADMA levels obtained in a group of relatively young AS patients who did not have classical CV risk factors suggest that NO metabolism is impaired in AS. On the other hand, anti-TNF treatments may have a beneficial effect on vascular function in AS.