Evaluation of serum omentin-1 and apelin concentrations in patients with hidradenitis suppurativa.

INTRODUCTION: Recent studies suggest a role of adipokines in the pathogenesis of hidradenitis suppurativa (HS). Omentin-1 and apelin are two recently identified adipokines that have been involved in the regulation of metabolic and inflammatory responses. AIM: To investigate serum omentin-1 and apelin levels in patients with HS and to assess their associations with metabolic parameters, disease severity and HS risk. MATERIAL AND METHODS: This case-control study included 139 non-diabetic individuals (78 HS patients and 61 ageand sex-matched controls). Serum concentrations of omentin-1 and apelin and the homeostasis model assessment of insulin resistance (HOMA-IR) were measured in all participants. RESULTS: Serum omentin-1 concentrations were significantly higher in HS patients compared to controls, whereas apelin serum levels did not significantly differ between both groups. These differences in omentin-1 concentrations remained significant even after adjusting for age, sex, and body mass index (BMI). The results of logistic regression analysis showed that increased omentin-1 plasma levels were an independent risk factor for HS. However, we found no association between serum levels of both omentin-1 and apelin with HS severity. CONCLUSIONS: Our results show that patients with HS have raised omentin-1 serum levels, which are associated with HS risk.

Association of retinol binding protein4 (RBP4) and ghrelin plasma levels with insulin resistance and disease severity in non-diabetic patients with hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease associated with insulin resistance (IR). Retinol binding protein 4 (RBP4) and ghrelin are two bioactive proteins that have been involved in glucose metabolism and IR, but also in the regulation of immune and inflammatory processes. The aim of this study was to determine the serum levels of RBP4 and ghrelin in patients with HS, and to assess the possible relationship between these levels and IR, disease severity and HS risk. A total of 137 subjects (77 HS patients and 60 controls) without diabetes mellitus were enrolled in this cross-sectional study. Patients with HS had significantly higher RBP4 but lower ghrelin plasma levels than controls, independently of body mass index (BMI). Serum RBP4 levels were positively correlated to disease severity and IR in HS patients. However, we found no association between ghrelin levels and any clinical or laboratory parameters. Moreover, high serum RBP4 and low ghrelin levels were associated with an increased risk for HS. Our results suggest that high RBP4 levels may be a surrogate biomarker for IR in patients with HS. Moreover, increased RBP4 and decreased ghrelin levels could also be independent risk factors for the development of HS.

Cardiovascular risk stratification in axial spondyloarthritis: carotid ultrasound is more sensitive than coronary artery calcification score to detect high-cardiovascular risk axial spondyloarthritis patients.

OBJECTIVES: To determine the ability of Coronary Artery Calcification Score (CACS) and carotid ultrasonography (US) to detect high cardiovascular (CV) risk axial spondyloarthritis (ax-SpA) patients. METHODS: CACS and carotid plaques were assessed in 66 consecutive ax-SpA patients (51 fulfilling criteria for ankylosing spondylitis and 15 for non-radiological ax-SpA) without history of CV events. The Systematic Coronary Risk Evaluation (SCORE) calculated using total cholesterol (TC-SCORE) was assessed in 64 patients without diabetes mellitus or chronic kidney disease. RESULTS: The mean age of the patients and the median disease duration since the onset of symptoms were 49.3 and 14.5 years. HLA-B27 was positive in 47 (75%) patients. CV risk was categorised according to the TC-SCORE as low (<1%; n=33), moderate (≥1% and<5%; n=30) and high/very high risk (≥5%; n=1). Most patients with low TC-SCORE (27/33; 82%) had normal CACS (zero), and only 1/33 had CACS >100. However, carotid plaques were observed in patients with CACS=0 (12/37; 32%) and CACS 1-100 (10/16; 62%). The sensitivity to detect high/very high CV risk using only the TC-SCORE was very low as the algorithm only detected 1/33 (3%) of patients with high/very high CV risk. Ten of 33 (30%) high/very high CV risk patients were identified using a chart TC-SCORE risk ≥5% plus the presence of CACS ≥100 in patients with moderate TC-SCORE. The replacement of CACS with carotid US identified a higher number of high/very high CV risk patients (22/33; 67%). CONCLUSIONS: Carotid US is more sensitive than CACS for the detection of high CV risk in ax-SpA patients.

Carotid ultrasound in the cardiovascular risk stratification of patients with ankylosing spondylitis: results of a population-based study.

OBJECTIVES: To determine if the use of carotid ultrasonography (US) may improve the cardiovascular (CV) risk stratification in patients with ankylosing spondylitis (AS). METHODS: A set of 127 consecutive patients without history of CV events, diabetes mellitus or chronic kidney disease that fulfilled definitions for AS according to the 1984 modified New York criteria were recruited to assess carotid intima-media thickness and presence of plaques. CV risk was calculated according to the systematic coronary risk evaluation (SCORE), the Framingham Risk Score (FRS) and the Reynolds Risk Score (RRS). RESULTS: Men outnumbered women (61.4%). The mean±SD age at the time of the study was 44.5±11.6 years. The median (interquartile range-IQR) disease duration was 13 (7-22) years. The median (IQR) BASDAI at the time of the study was 3.65 (1.7- 4.9). HLA-B-27 was positive in 77.2%, and syndesmophytes were present in 38.9%. Carotid plaques were found in 43 (33.9%). Regardless of the algorithm used for CV risk stratification, more than 50% of the patients classified as having moderate CV risk had carotid plaques. Moreover, 20.8%, 24.6% and 53.3% of AS that fulfilled the category of low CV risk according to the total cholesterol (TC)-SCORE, FRS and RRS, respectively had carotid plaques. A model that included patients with a chart TC-SCORE ≥5% or TC-SCORE ≥1% <5% plus carotid plaques or TC-SCORE <1% and CRP >3 mg/L at diagnosis plus syndesmophytes and carotid plaques or TC-SCORE <1% and CRP >3 mg/L at diagnosis plus extraarticular manifestations plus carotid plaques yielded the highest sensitivity (93.0%) for high/very high CV risk in these patients. The presence of syndesmophytes was associated with increased risk of carotid plaques in AS that fulfilled definitions for low CV risk according to the TC-SCORE (OR 8.75 [95% CI 2.11-36.40]; p=0.002). CONCLUSIONS: Our results support the use of carotid US in the assessment of CV risk in patients with AS.

Increased prevalence of subclinical atherosclerosis in patients with hidradenitis suppurativa (HS).

BACKGROUND: Chronic inflammatory diseases have been associated with increased prevalence of subclinical atherosclerosis. Hidradenitis suppurativa (HS) is a chronic inflammatory disease involving intertriginous skin. OBJECTIVE: We sought to investigate the potential association between HS and subclinical atherosclerosis. METHODS: This study included 68 patients with HS and 136 age- and sex-matched healthy control subjects. Patients with history of cardiovascular events, diabetes mellitus, chronic kidney disease, or another concomitant inflammatory condition were excluded. Carotid intima-media thickness and carotid plaques were measured by carotid ultrasonography. Adjustments were made for age, sex, and traditional cardiovascular risk factors. RESULTS: Patients had greater carotid intima-media thickness values than control subjects (0.615 ± 0.097 vs 0.578 ± 0.098 mm; P = .012). Carotid plaques were also more frequent in patients than in control subjects (30.9% vs 22.1%). In the multivariable regression model adjusted for age, sex, and traditional cardiovascular risk factors, HS was significantly related to the presence of carotid plaques (odds ratio 2.99, 95% confidence interval 1.26-7.13; P = .013). LIMITATIONS: Causality could not be assessed. CONCLUSIONS: These results indicate an increased frequency of subclinical atherosclerosis in patients with HS. Accordingly, HS should be considered a disease associated with potentially increased cardiovascular risk.

Coexistence of Hidradenitis Suppurativa with Autoimmune Thyroiditis: Report of Three Cases.

Hidradenitis suppurativa (HS) is a chronic, relapsing inflammatory skin disease affecting terminal hair follicles in apocrine-gland-bearing skin. The pathogenesis of HS is still unknown, although increasing evidence suggests that the immune system plays an important role. Herein we describe 3 patients with HS coexisting with autoimmune (Hashimoto's) thyroiditis (AT). To our knowledge, the co-occurrence of these two diseases has not previously been described. The coexistence of HS with autoimmune disorders, such as AT, may support the hypothesis on dysregulation of the immune system's function as implicated in the pathogenesis of HS. Based on our findings, we feel that an assessment of thyroid function and antithyroid antibodies should be performed in patients with HS.

Atherosclerotic disease in axial spondyloarthritis: increased frequency of carotid plaques.

OBJECTIVES: To establish whether subclinical atherosclerosis is increased in patients with axial spondyloarthritis (ax-SpA). METHODS: A set of 149 consecutive patients with no history of cardiovascular disease that fulfilled the Assessment of SpondyloArthritis International Society classification criteria for ax-SpA was studied by carotid ultrasonography. Carotid intima-media thickness (cIMT) and plaques were assessed. A series of 181 community-based controls with no cardiovascular disease were studied for comparison. To establish whether ax-SpA might have a direct effect on the risk of carotid plaques or an indirect effect via its putative influence on hypertension, dyslipidaemia or obesity, we obtained adjusted odds ratios (OR) for each clinical factor by the development of adjusted models. RESULTS: cIMT was increased in patients (0.621±0.123 mm) when compared to controls (0.607±0.117 mm) but the difference was not significant (p=0.30). Nevertheless, carotid plaques were more commonly observed in patients with ax-SpA than in controls (41.6% vs. 26.4%; p=0.003). Patients with plaques had longer duration of the disease than those without plaques (20.5±11.2 years vs. 12.0±8.6 years; p<0.001). Plaques were more frequent in patients with hip involvement (crude odds ratio 3.15, 95% confidence interval [CI] 1.02-9.75; p=0.05), syndesmophytes (crude OR 4.94, 95% CI 2.14-11.4; p<0.001), in patients with higher functional limitation and mobility index measured by BASFI (crude OR 1.16, 95% CI 1.02-1.33; p=0.03) and BASMI (crude OR 1.45, 95% CI 1.19-1.77; p<0.001), and in those with psoriasis (crude OR 3.94, 95% CI 1.31-11.84; p=0.02. However, except for psoriasis that continued being a strong risk factor for plaques after adjustment, the relationship between other clinical features of ax-SpA and carotid plaques disappeared in the adjusted models. CONCLUSIONS: Our results confirm the presence of subclinical atherosclerosis in patients with ax-SpA.

Influence of interleukin 10 promoter polymorphisms in polymyalgia rheumatica: disease susceptibility and functional consequences.

OBJECTIVES: To investigate the functional consequences of IL10 (-592C/A and -1082A/G) gene polymorphisms and their association with susceptibility to, and disease phenotype, in patients with polymyalgia rheumatica (PMR). METHODS: A total number of 168 with PMR and 124 age-matched controls were genotyped using allele-specific primers and restriction fragment length polymorphism analysis. The levels of circulating IL10 and the production of IL10 by PBMCs after in vitro stimulation were studied by Cytometric Bead Array. RESULTS: No significant differences were observed in genotype or allele frequency distribution between patients and controls. The clinical characteristics and prognosis of these patients were also unrelated to the presence of these polymorphisms. No significant differences between PMR patients with low ESR (<40 mm/hr) and classic PMR (>40 mm/hr) were found. Furthermore, we did not observe any influence of circulating IL10 with the intensity of the acute phase response. In both, PMR patients and age-matched controls, no differences in circulating IL10 levels or IL10 production were observed depending on the genotypes of the IL10 gene. CONCLUSIONS: These results do not support the impact of IL10 variants in susceptibility or clinical phenotype of PMR patients. In this aged population no functional association was found between IL10 gene variants and IL10 production.

Revisiting clinical differences between hypersensitivity vasculitis and Henoch-Schönlein purpura in adults from a defined population.

OBJECTIVES: Hypersensitivity vasculitis (HV) and Henoch-Schönlein purpura (HSP) are the most common entities included within the category of cutaneous vasculitis (CV). Palpable purpura and histological changes characterised by the presence of leukocytoclastic vasculitis are common in both conditions. Therefore, considerable overlap between them is often seen. It is especially true when the CV occurs in adults. To further establish clinical differences between these two conditions, in the present study we assessed the main clinical differences between HV and HSP in a wide and unselected series of adults with CV from a defined population. METHODS: We reviewed the clinical records of 297 consecutive adults (age >20 years) seen at a single centre between January 1975 and December 2012 that were classified as having HSP or HV according to the criteria proposed by Michel et al. (J Rheumatol 1992; 19: 721-8). RESULTS: Based on the inclusion criteria, 102 adult patients (71 men/31 women) were classified as HSP and 195 (104 men/91 women) as HV. The mean age was similar in both groups (55.8±16.5 years in HSP and 56.8±18.3 years in HV). Precipitating events, usually an upper respiratory tract infection and/or drug intake, were more frequently observed in HV. Both at the beginning of the disease and when the CV was established clinical manifestations were more frequent in patients with HSP than in those with HV. It was the case for gastrointestinal (57.4% vs. 6.8%; p<0.001), joint (51.5% vs. 36.6%; p=0.01) and renal involvement (86.3% vs. 18.3%; p<0.001). Corticosteroid (56.7% vs. 22%; p<0.001) and cytotoxic drug (19.4% vs. 3.2%; p<0.001) use was also more common in patients with HSP. After a median follow-up of 15.5 (interquartile range- IQR; 3-37) months in HSP and 4 (IQR; 2-12) months in HV, the outcome was better in HV than in HSP. In this regard, complete recovery (72.6% vs. 85.4%; p=0.01) was more commonly observed in HV while residual renal involvement (15.3% vs. 4.2%; p<0.001) was more common in HSP. The disease relapsed in 35.3% of patients with HSP and in 24.4% with HV (p=0.07). CONCLUSIONS: Our results confirm the claim that these two diseases presenting with similar cutaneous involvement are certainly two separate entities with greater systemic involvement and less favourable outcome in HSP.

Tocilizumab in refractory aortitis: study on 16 patients and literature review.

OBJECTIVES: Non-infectious aortitis is often refractory to standard immunosuppressive therapy. Since IL-6 has been implicated in the pathogenesis of aortitis, we assessed the efficacy of the anti-IL6 receptor monoconal antibody tocilizumab (TCZ) in a series of patients with refractory non-infectious aortitis. METHODS: Review of 16 patients (14 women/2 men) with refractory aortitis diagnosed by imaging (CT angiography, MR angiography, and/or PET) that were treated with TCZ. RESULTS: The mean age±SD was 51.4±20.1 years. The underlying conditions were: Takayasu arteritis (TakA) (n=7 cases), giant cell arteritis (GCA) (n=7), relapsing polychondritis (RP) (n=1), and aortitis associated with retroperitoneal fibrosis (n=1). TCZ was the first biologic drug used in all patients with GCA and in the patient with aortitis associated with retroperitoneal fibrosis but in only 2 of 7 TakA patients. In the remaining cases anti-TNF inhibitors were prescribed before TCZ (standard dose was 8 mg/kg/iv/4 weeks). After a mean±SD follow-up of 11.8±6.6 months most patients experienced clinical improvement, showing reduction of erythrocyte sedimentation rate from 43±36 mm/1st h to 5±4 mm/1st h at last visit. At TCZ onset, 25% of patients had fever and 19% polymyalgia rheumatica. These manifestations disappeared after 3 months of TCZ therapy. A corticosteroid sparing effect was also achieved (from 27.3±17.6 mg/day of prednisone at TCZ onset to 4.2±3.8 mg/day at last visit). TCZ had to be discontinued in a patient because of severe neutropenia. CONCLUSIONS: TCZ appears to be effective and relatively safe in patients with inflammatory aortitis refractory to corticosteroids or to other biologic immunosuppressive drugs.

Organotypic 3D Cell-Architecture Impacts the Expression Pattern of miRNAs-mRNAs Network in Breast Cancer SKBR3 Cells.

BACKGROUND: Currently, most of the research on breast cancer has been carried out in conventional two-dimensional (2D) cell cultures due to its practical benefits, however, the three-dimensional (3D) cell culture is becoming the model of choice in cancer research because it allows cell-cell and cell-extracellular matrix (ECM) interactions, mimicking the native microenvironment of tumors in vivo. METHODS: In this work, we evaluated the effect of 3D cell organization on the expression pattern of miRNAs (by Small-RNAseq) and mRNAs (by microarrays) in the breast cancer SKBR3 cell line and analyzed the biological processes and signaling pathways regulated by the differentially expressed protein-coding genes (DE-mRNAs) and miRNAs (DE-microRNAs) found in the organoids. RESULTS: We obtained well-defined cell-aggregated organoids with a grape cluster-like morphology with a size up to 9.2 × 105 µm3. The transcriptomic assays showed that cell growth in organoids significantly affected (all p < 0.01) the gene expression patterns of both miRNAs, and mRNAs, finding 20 upregulated and 19 downregulated DE-microRNAs, as well as 49 upregulated and 123 downregulated DE-mRNAs. In silico analysis showed that a subset of 11 upregulated DE-microRNAs target 70 downregulated DE-mRNAs. These genes are involved in 150 gene ontology (GO) biological processes such as regulation of cell morphogenesis, regulation of cell shape, regulation of canonical Wnt signaling pathway, morphogenesis of epithelium, regulation of cytoskeleton organization, as well as in the MAPK and AGE-RAGE signaling KEGG-pathways. Interestingly, hsa-mir-122-5p (Fold Change (FC) = 15.4), hsa-mir-369-3p (FC = 11.4), and hsa-mir-10b-5p (FC = 20.1) regulated up to 81% of the 70 downregulated DE-mRNAs. CONCLUSION: The organotypic 3D cell-organization architecture of breast cancer SKBR3 cells impacts the expression pattern of the miRNAs-mRNAs network mainly through overexpression of hsa-mir-122-5p, hsa-mir-369-3p, and hsa-mir-10b-5p. All these findings suggest that the interaction between cell-cell and cell-ECM as well as the change in the culture architecture impacts gene expression, and, therefore, support the pertinence of migrating breast cancer research from conventional cultures to 3D models.

Sex differences in cardiovascular and disease-related features in axial spondyloarthritis. A multicenter study of 912 patients.

OBJECTIVES: To determine the potential impact of sex-specific disease-related characteristics on cardiovascular (CV) disease in axial spondyloarthritis (axSpA). METHODS: Cross-sectional study of the Spanish AtheSpAin cohort to study CV disease in axSpA. Data on carotid ultrasound and CV disease and disease-related features were collected. RESULTS: 611 men and 301 women were recruited. Classic CV risk factors were significantly less prevalent in women, who also showed a lower frequency of carotid plaques (p = 0.001), lower carotid intima-media thickness (IMT) values ​​(p<0.001) and CV events (p = 0.008). However, after adjustment for classic CV risk factors, only the differences with respect to carotid IMT remained statistically significant. Women showed higher ESR at diagnosis (p = 0.038), and more active disease (ASDAS, p = 0.012, and BASDAI, p<0.001). They had shorter disease duration (p<0.001), lower prevalence of psoriasis (p = 0.008), less structural damage (mSASSS, p<0.001), and less mobility limitation (BASMI, p = 0.033). To establish whether these findings could lead to sex differences in CV disease burden, we compared the prevalence of carotid plaques in men and women with the same level of CV risk stratified according to the Systematic Coronary Risk Evaluation (SCORE). Men included in the low-moderate CV risk SCORE category had more carotid plaques (p = 0.050), along with longer disease duration (p = 0.004), higher mSASSS (p = 0.001) and psoriasis (p = 0.023). In contrast, in the high-very high-risk SCORE category, carotid plaques were observed more frequently in women (p = 0.028), who were characterized as having worse BASFI (p = 0.011), BASDAI (p<0.001) and ASDAS (p = 0.027). CONCLUSION: Disease-related features may influence the expression of atherosclerosis in patients with axSpA. This may be especially applicable to women at high CV risk, characterized by greater disease severity and more severe subclinical atherosclerosis than men, suggesting a stronger interaction between disease activity and atherosclerosis in women with axSpA.

Status of vitamin D in children with sickle cell disease living in Madrid, Spain.

UNLABELLED: Patients with sickle cell disease have vitamin D deficiency and poor bone health which makes them prone to have an increased risk of fractures and osteoporosis in adulthood. We performed a prospective, cross-sectional study in children diagnosed with sickle cell disease living in Madrid, Spain. The purpose of this study was to evaluate the status of vitamin D of these children. Patients 0-16 years old were enrolled between 2008 and 2011. We studied demographics, calcium metabolism, and bone health, especially by measuring levels of 25-hydroxyvitamin D (25(OH)D), during different seasons of the year, and bone densitometry (beyond 4 years of age). Seventy-eight children were included in the study. Mean age was 4.8 ± 4.3 years, and mean serum 25(OH)D level was 21.50 ± 13.14 ng/ml, with no differences in 25(OH)D levels within different seasons. Fifty-six percent of children had levels of 25(OH) vitamin D of <20 ng/ml, whereas 79 and 18 % of them had levels of <30 and <11 ng/ml, respectively. Secondary hyperparathyroidism was observed in 25 % of children. Densitometry was performed in 33 children, and an abnormal z-score was seen in 15.2 % of them with no correlation with levels of 25(OH)D. CONCLUSIONS: Vitamin D deficiency is highly prevalent in children with sickle cell disease, who are residing in Madrid, Spain, and it is detected at a young age. We propose that early intervention may increase the possibility of an adequate bone density later in life.

The influence of traffic noise on vertebrate road crossing through underpasses.

Noise produces multiple effects on ecosystems and it influences habitat use by vertebrates near roads. Thus, it may reduce the effectiveness of mitigation measures installed on roads to alleviate population fragmentation. This study analyses the effects of noise on the use by vertebrates of 19 underpasses at a motorway. It employs generalised linear models to test the effect of three noise indicators at the underpasses and in their vicinity on the crossing frequency of eight animal species. The results show that the road crossings are subjected to high and variable noise levels. Nevertheless, there is no consistent response to noise by vertebrates. This suggests that wildlife use of underpasses is determined more by habitat characteristics than by the levels of noise tolerated. The conclusion is that noise abatement measures on roads in areas of faunal sensitivity should focus on general noise reduction rather than on making individual crossing places quieter.

Biomarkers of endothelial dysfunction and atherosclerosis in hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease associated with an increased prevalence of subclinical atherosclerosis and cardiovascular risk. Angiopoietin-2 (Ang-2), asymmetric dimethylarginine (ADMA), and osteoprotegerin (OPG) are molecules related to endothelial dysfunction (ED) and atherosclerosis, but also to disease severity in patients with chronic inflammatory disorders. In this case-control study, we aimed to investigate serum Ang-2, ADMA, and OPG levels in patients with HS, and to assess the potential relationship between these levels and disease severity. Seventy-five patients with HS and 60 controls were assessed. Serum Ang-2, ADMA, and OPG concentrations were determined in all participants. HS patients had significantly higher Ang-2 and ADMA levels than controls after adjusting for confounders. Besides, Ang-2 concentrations positively correlated with disease severity in the adjusted multivariable analysis. Nevertheless, serum OPG levels did not significantly differ between HS patients and controls. Our results indicate that serum Ang-2 and ADMA levels are significantly increased in patients with HS. Furthermore, Ang-2 might be a suitable marker of HS severity.

Irisin as a Novel Biomarker of Subclinical Atherosclerosis, Cardiovascular Risk and Severe Disease in Axial Spondyloarthritis.

Introduction: Patients with axial spondyloarthritis (axSpA) have a high disease burden mainly due to the rheumatic disease itself, and also exhibit accelerated atherosclerosis, that leads to a higher incidence of cardiovascular (CV) disease. Accordingly, the identification of biomarkers of CV risk and inflammation in axSpA patients is clinically relevant. In this sense, given the beneficial functions exerted by the adipomyokine irisin in processes related to CV disease and inflammation, our aim was to assess, for the first time, the role of irisin as a genetic and serological biomarker of subclinical atherosclerosis, CV risk and disease severity in axSpA patients. Methods: A large cohort of 725 Spanish patients with axSpA was included. Subclinical atherosclerosis (presence of plaques and abnormal carotid intima-media thickness values) was evaluated by carotid ultrasound. Four irisin polymorphisms (rs16835198 G/T, rs3480 A/G, rs726344 G/A, and rs1570569 G/T) were genotyped by TaqMan probes. Additionally, serum irisin levels were determined by ELISA. Results: Low irisin levels were linked to the presence of plaques (p=0.002) and atherogenic index values ≥4 (p=0.01). Serum irisin were positively correlated with C-peptide levels (p<0.001) and negatively correlated with visual analogue scale and Bath Ankylosing Spondylitis Metrology Index (p<0.05 in all the cases). Moreover, lower irisin levels were observed in patients with sacroiliitis and in those with a negative HLA-B27 status (p<0.001 and p=0.006, respectively), as well as in those treated with non-steroidal anti-inflammatory drugs and conventional disease-modifying antirheumatic drugs (p<0.001 and p=0.002, respectively). Interestingly, the TT genotype and the T allele of rs16835198 were less frequent in axSpA patients with ASDAS >2.1 (Odds Ratio (OR): 0.48 [0.28-0.83] and OR: 0.73 [0.57-0.92], respectively, p=0.01 in both cases). Additionally, the frequency of rs1570569 T allele was higher in these patients (OR: 1.46 [1.08-1.97], p=0.01). Furthermore, the GGGT haplotype was more frequent in patients with ASDAS values >2.1 (OR: 1.73 [1.13-2.66], p=0.01). Conclusions: Our results indicate that low serum irisin levels could be indicators of the presence of subclinical atherosclerosis, high CV risk and more severe disease in axSpA patients. In addition, irisin may also constitute a genetic biomarker of disease activity in axSpA.

Expression and function of toll-like receptors in peripheral blood mononuclear cells of patients with polymyalgia rheumatica and giant cell arteritis.

OBJECTIVE: To investigate the expression and function of the Toll-like receptor (TLR) family in peripheral blood mononuclear cells (PBMCs) of patients with polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). METHODS: The authors analysed 70 patients with PMR, 20 with GCA, and 24 healthy controls (HC). TLR expression was assessed by flow cytometry. TLR function was assessed by stimulating PBMCs with specific ligands. RESULTS: A significantly increased expression of TLR7 in PBMCs of patients with active disease compared with HC was found. Despite increased expression of TLR7, circulating monocytes from patients showed a significantly lower in vitro response to TLR7 agonists. No amino acid substitutions predicted to be functionally damaging were found in TLR7. A normal response to specific TLR7 agonists in patients in complete remission eliminated a genetic defect. TLR expression and function were also affected to some degree in other diseases characterised by a strong acute phase response. CONCLUSION: These data suggest activation of TLR7 during the active phase of PMR and GCA which resolves with complete disease remission. Whether this finding is the consequence of the marked inflammatory process in these disorders or activation by natural ligands remains to be explored.

Lack of association between Toll-like receptor 4 gene polymorphisms and giant cell arteritis.

OBJECTIVE: Coding variants in Toll-like receptor 4 (TLR4) have been reported to be associated with inflammatory diseases. The aim of this study was to determine whether two of these polymorphisms (+896 A/G and +1196 C/T) are associated with susceptibility and clinical features of GCA. We also attempted to correlate the functional consequences of these polymorphisms. METHODS: A total of 72 patients with GCA and 126 age-matched controls were genotyped using allele-specific PCR and restriction fragment length polymorphism analysis. TLR4 expression was studied on peripheral blood mononuclear cells by flow cytometry and TLR4 function was assessed by stimulating monocytes in vitro with a specific ligand. RESULTS: There was no significant difference in allele frequency or genotype of TLR4 (+896 A/G and +1196 C/T) between GCA patients and controls. The clinical characteristics of these patients were unrelated to the presence of these polymorphisms. Furthermore, we did not observe an association with TLR4 expression or a distinct phenotype of TLR4 response with the +896 A/G and +1196 C/T genotypes. CONCLUSION: Our results do not support the association of these TLR4 variants with GCA. Studies including a larger number of patients and patient populations from different geographical origin are needed.