Insulin resistance in non-diabetes patients with spondyloarthritis.

Objectives: Insulin resistance (IR) constitutes a major underlying abnormality driving cardiovascular disease in the general population and has been linked to inflammatory diseases. In this study, we aimed to determine the prevalence of IR in patients with spondyloarthritis (SpA) and whether IR can be explained by disease-related features in such cases. Method: The study included 577 subjects: 306 patients diagnosed with SpA according to Assessment of SpondyloArthritis international Society criteria and 271 controls. Insulin and C-peptide serum levels, IR and ß-cell function (%B) indices by homoeostatic model assessment (HOMA2), and lipid profiles were assessed in patients and controls. A multivariable regression analysis was performed to evaluate the differences in IR indices between patients and controls and to determine how IR is associated with disease-related characteristics in SpA patients. Results: HOMA2-%B and HOMA2-IR scores, both calculated with insulin or C-peptide, had significantly higher values in SpA patients compared to controls in multivariable analysis adjusted for age, gender, traditional IR-related factors, and glucocorticoid intake. Disease activity, functional status, and metrological SpA indices were positively related to IR, but only in univariable analysis. Disease duration and positivity for human leucocyte antigen-B27 were independently associated with a higher HOMA2-%B after multivariable analysis. Conclusion: Patients with SpA have an increased IR compared to controls. SpA disease-related data are independently associated with ß-cell dysfunction.

Insulin resistance in hidradenitis suppurativa: a case-control study.

BACKGROUND: The association between chronic inflammatory diseases, such as rheumatoid arthritis and psoriasis, and insulin resistance (IR) has been well established. Hidradenitis suppurativa (HS) is a chronic inflammatory cutaneous disease that affects the apocrine gland-bearing areas of the body. OBJECTIVE: We aimed to determine the prevalence of IR in patients with HS. METHODS: This cross-sectional, case-control study enrolled 137 subjects, 76 patients with HS and 61 age- and gender-matched controls. Demographic data, clinical examination of HS patients, anthropometric measures, cardiovascular risk factors and laboratory studies were recorded. The homeostasis model assessment of IR (HOMA-IR) was calculated in all participants by measuring fasting plasma glucose and insulin levels. RESULTS: The median (IQR) HOMA-IR value in HS patients was significantly higher [2.0 (1.0-3.6)] than in controls [1.5 (0.9-2.3)] (P = 0.01). The prevalence of IR was significantly higher in cases (43.4%) compared with controls (16.4%) (P = 0.001). In the linear regression multivariable analysis after adjusting for age, sex and body mass index (BMI), HS remained as a significant factor for a higher HOMA-IR [2.51 (0.18) vs 1.92(0.21); P = 0.04]. The HOMA-IR value and the prevalence of IR did not differ significantly among HS patients grouped by severity of the disease. CONCLUSION: Our results show an increased frequency of IR in HS. Thus, we suggest HS patients to be evaluated for IR and managed accordingly.

EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update.

Patients with rheumatoid arthritis (RA) and other inflammatory joint disorders (IJD) have increased cardiovascular disease (CVD) risk compared with the general population. In 2009, the European League Against Rheumatism (EULAR) taskforce recommended screening, identification of CVD risk factors and CVD risk management largely based on expert opinion. In view of substantial new evidence, an update was conducted with the aim of producing CVD risk management recommendations for patients with IJD that now incorporates an increasing evidence base. A multidisciplinary steering committee (representing 13 European countries) comprised 26 members including patient representatives, rheumatologists, cardiologists, internists, epidemiologists, a health professional and fellows. Systematic literature searches were performed and evidence was categorised according to standard guidelines. The evidence was discussed and summarised by the experts in the course of a consensus finding and voting process. Three overarching principles were defined. First, there is a higher risk for CVD in patients with RA, and this may also apply to ankylosing spondylitis and psoriatic arthritis. Second, the rheumatologist is responsible for CVD risk management in patients with IJD. Third, the use of non-steroidal anti-inflammatory drugs and corticosteroids should be in accordance with treatment-specific recommendations from EULAR and Assessment of Spondyloarthritis International Society. Ten recommendations were defined, of which one is new and six were changed compared with the 2009 recommendations. Each designated an appropriate evidence support level. The present update extends on the evidence that CVD risk in the whole spectrum of IJD is increased. This underscores the need for CVD risk management in these patients. These recommendations are defined to provide assistance in CVD risk management in IJD, based on expert opinion and scientific evidence.

Corticoids synergize with IL-1 in the induction of LCN2.

OBJECTIVE: Lipocalin-2 (LCN2) is an adipokine that was first identified in neutrophil granules. In the last years it was recognized as a factor that could impair chondrocyte phenotype, cartilage homeostasis as well as growth plate development. Both pro-inflammatory cytokines and glucocorticoids (GCs) modulate LCN2 expression. Actually, GCs were found to be LCN2 inducers, suggesting that part of the negative actions exerted by these anti-inflammatory drugs at cartilage level could be mediated by this adipokine. So, in this study we wanted to investigate whether corticoids were able to act in synergy with IL-1 in the induction of LCN2 and the signaling pathway involved in this process. MATERIALS AND METHODS: For the realization of this work, ATDC5 mouse chondrogenic cell line was used. We determined the mRNA and protein expression of LCN2 by real-time reverse transcription-polymerase chain reaction (RT-qPCR) and western blot respectively, after GC or mineralcorticoid treatment. Different signaling pathways inhibitors were also used. RESULTS: GC and mineralcorticoid were able to induce the expression of LCN2 in ATDC5 cells. Interestingly, both corticoids synergized with IL-1 in the induction of LCN2. The effect of these corticoids on the expression of LCN2 occurred through GC or mineralcorticoid receptors and the kinases PI3K, ERK1/2 and JAK2. CONCLUSIONS: Prolonged use of corticoids may have detrimental effects on cartilage homeostasis. Based on our results, we conclude that corticoids could increase the negative actions exerted by IL-1 by increasing the expression of LCN2.

Thyroid autoimmunity in patients with hidradenitis suppurativa: a case-control study.

The aetiopathogenesis of hidradenitis suppurativa (HS) is not fully understood; however, increasing evidence suggests that it may be an immune-mediated disorder. Autoimmune thyroid disease (AITD) has classically been considered as the 'paradigm' of autoimmunity, and it has been linked to a variety of skin disorders. To our knowledge, the prevalence of AITD has not been investigated in patients with HS. The aim of the present study was to assess and compare, for the first time, the prevalence of thyroid autoimmunity in 70 patients with HS and in 70 age- and sex-matched controls. In all participants, thyroid autoantibodies and thyroid function tests were analysed. No statistically significant difference was detected between patients with HS and controls, either for the prevalence of thyroid antibodies or for thyroid function parameters. This lack of an association between HS and thyroid autoimmunity suggests that conventional autoimmune mechanisms may not be implicated in the pathogenesis of HS.

Anti-TNF-α therapy reduces retinol-binding protein 4 serum levels in non-diabetic patients with psoriasis: a 6-month prospective study.

BACKGROUND: Retinol-binding protein-4 (RBP4), an adipokine considered as an emerging cardiometabolic risk factor, is increased in patients with moderate-to-severe psoriasis. OBJECTIVE: In this study, we aimed to establish the effect of anti-TNF-α therapy on RBP4 levels in patients with moderate-to-severe psoriasis. We also assessed if RBP4 levels correlate with metabolic syndrome features and disease severity in these patients. METHODS: Prospective study on a series of consecutive non-diabetic patients with moderate-to-severe psoriasis who completed 6 months of therapy with adalimumab. Patients with kidney disease, hypertension or body mass index ≥ 35 kg/m(2) were excluded. Metabolic and clinical evaluation was performed at the onset of treatment (time 0) and at month 6. RESULTS: Twenty-nine patients were assessed. Statistically significant reduction (P = 0.0001) of RBP4 levels was observed after 6 months of therapy (RBP4 at time 0: 55.7 ± 21.4 µg/mL, vs. 35.6 ± 29.9 µg/mL at month 6). No significant correlation between basal RBP4 levels and metabolic syndrome features or disease severity was found. Nevertheless, although RBP4 levels did not correlate with insulin resistance, a negative and significant correlation between RBP4 levels obtained after 6 months of adalimumab therapy and other metabolic syndrome features such as abdominal perimeter and body mass index were observed. At that time, a negative and significant correlation between RBP4 levels and disease activity scores and ultrasensitive CRP levels was also disclosed. CONCLUSION: Our results support an influence of the anti-TNF-α blockade on RBP4 serum levels. This finding is of potential relevance due to increased risk of cardiovascular disease in patients with psoriasis.

Cutaneous vasculitis associated with severe bacterial infections. A study of 27 patients from a series of 766 cutaneous vasculitis.

OBJECTIVES: To assess the clinical spectrum of severe bacterial infections presenting as cutaneous vasculitis (CV) in a defined population. METHODS: Unselected series of 766 patients with CV diagnosed at a single university referral center. RESULTS: An underlying severe bacterial infection was diagnosed in 27 (22 men/5 women; mean age ± standard deviation [SD]: 53 ± 18 years) of 766 cases presenting with CV (3.5%). These infections were: pneumonia (n=8), endocarditis (n=6), meningitis (n=4), intra-abdominal infections (n=3), septic arthritis (n=2), septicaemia (n=2), septic bursitis (n=1), and urinary tract infection (n=1). All the patients were admitted for suspected CV. The median delay from admission to the diagnosis of infection was 4 days. A typical palpable purpura without relevant visceral vasculitic involvement was the main clinical manifestation. Patients with severe bacterial infections were older, with male predominance, had more frequently fever, constitutional symptoms, focal infectious features, and leukocytosis with left shift and anaemia than the remaining patients with CV. Although antibiotics were prescribed in all the patients, seven also required the use of low-dose corticosteroids to achieve complete resolution of the cutaneous lesions. Most patients experienced full recovery but two of them underwent prosthetic cardiac valve replacement, and another two died due to infection-related complications. CONCLUSIONS: CV may be the presenting manifestation of a severe underlying bacterial infection. Physicians should keep in mind this fact to make an early diagnosis of infection and, consequently, prevent life-threatening complications.

Non-infectious aortitis: a report of 32 cases from a single tertiary centre in a 4-year period and literature review.

OBJECTIVES: Non-infectious aortitis often presents with non-specific symptoms leading to inappropriate diagnostic delay. We intend to describe the clinical spectrum and outcome of patients with aortitis diagnosed at a single centre. METHODS: We reviewed the clinical charts of patients diagnosed with non-infectious aortitis between January 2010 and December 2013 at the Rheumatology Division from a 1.000-bed tertiary teaching hospital from Northern Spain. The diagnosis of aortitis was usually based on FDG-PET-CT scan, and also occasionally on CT or MRI angiography or helical CT-scan. RESULTS: During the period of assessment 32 patients (22 women and 10 men; mean age 68 years [range, 45-87]) were diagnosed with aortitis. The median interval from the onset of symptoms to the diagnosis was 21 months. FDG-PET CT scan was the most common tool used for the diagnosis of aortitis. The underlying conditions were the following: giant cell arteritis (n=13 cases); isolated polymyalgia rheumatica (PMR) (n=11); Sjögren's syndrome (n=2), Takayasu arteritis (n= 1); sarcoidosis (n=1), ulcerative colitis (n=1), psoriatic arthritis (n=1), and large-vessel vasculitis that also involved the aorta (n=2). The most common clinical manifestations at diagnosis were: PMR features, often with atypical clinical presentation (n=23 patients, 72%); diffuse lower limb pain (n=16 patients, 50%); constitutional symptoms (n=12 patients, 37%), inflammatory low back pain (n=9 patients, 28%) and fever (n=7 patients, 22%). Acute phase reactants were increased in most cases (median erythrocyte sedimentation rate 46 mm/1st hour, and a median serum C-reactive protein 1.5 mg/dL). CONCLUSIONS: Aortitis is not an uncommon condition. The diagnosis is often delayed. Atypical PMR features, unexplained low back or limb pain, constitutional symptoms along with increased acute phase reactants should be considered 'red flags' to suspect the presence of aortitis.

Applicability of the 2006 European League Against Rheumatism (EULAR) criteria for the classification of Henoch-Schönlein purpura. An analysis based on 766 patients with cutaneous vasculitis.

OBJECTIVES: In 2006 the European League Against Rheumatism (EULAR) proposed new classification criteria for Henoch-Schönlein purpura (HSP). We aimed to establish the applicability of these criteria in patients with primary cutaneous vasculitis (CV). We also compared these criteria with previously established classification criteria for HSP. METHODS: A series of 766 (346 women/420 men; mean age 34 years) consecutive unselected patients with CV was assessed. One hundred and twenty-four of them with secondary CV or with CV associated with other well defined entities were excluded from the analysis. The 2006 EULAR criteria for HSP were tested in the remaining 642 patients with primary CV. Two sets of criteria for HSP were used for comparisons: a) the 1990 American College of Rheumatology (ACR-1990), and b) the ACR modified criteria proposed by Michel et al. in 1992 (Michel-1992). RESULTS: 451 (70.2%) of 642 patients were classified as having HSP according to the EULAR-2006 criteria, 405 (63.1%) using the ACR-1990 criteria, and 392 (61.1%) by the Michel-1992 criteria. However, only 336 patients (52.3%) met at the same time the EULAR-2006 and the ACR-1990 criteria, and only 229 patients (35.7%) fulfilled both the EULAR-2006 and Michel-1992 criteria. It is noteworthy that only 276 (43%) patients met the three set of criteria. Children fulfilled all the sets of criteria more commonly than adults (215 [66.6%] of 323 vs. 61 [19%] of 319, respectively; p<0.0001). CONCLUSIONS: According to our results, the EULAR-2006 criteria show low concordance with previous sets of classification criteria used for HSP.

Anti-TNF-α therapy improves insulin sensitivity in non-diabetic patients with psoriasis: a 6-month prospective study.

OBJECTIVE: Psoriasis is a chronic inflammatory disease associated with increased risk of cardiovascular death. Several studies have shown a beneficial effect of anti-TNF-α therapy on the mechanisms associated with accelerated atherogenesis in patients with inflammatory arthritis, including an improvement of insulin sensitivity. In this study, we aimed to determine for the first time whether the anti-TNF-α monoclonal antibody adalimumab may improve insulin sensitivity in non-diabetic patients with psoriasis. METHODS: Prospective study on a series of consecutive non-diabetic patients with moderate to severe psoriasis seen at the Dermatology Division of Hospital Universitario Marques de Valdecilla (Northern Spain) who completed 6 months of therapy with adalimumab (80 mg at week 0 followed by 40 mg every other week, starting 1 week after the initial dose). Patients with chronic kidney disease, hypertension or body mass index ≥ 35 kg/m(2) were excluded. Metabolic and clinical evaluation including assessment of insulin sensitivity using the Quantitative Insulin Sensitivity Check Index (QUICKI) was performed at the onset of the treatment (time 0) and at month 6. RESULTS: Twenty-nine patients (52% women; 38.6 ± 10.7 years) with moderate to severe psoriasis [body surface area (BSA) 37.9 ± 16.3%], Psoriasis Area and Severity Index [(PASI) 18.9 ± 7.8] were assessed. Statistically significant improvement (P=0.008) of insulin sensitivity was observed after 6 months of adalimumab therapy (QUICKI at time 0: 0.35 ± 0.04 vs. 0.37 ± 0.04 at month 6). Significant improvement of erythrocyte sedimentation rate, ultrasensitive C-reactive protein, BSA, PASI, Nail Psoriasis Severity Index, physician global assessment and psoriatic arthritis screening and evaluation questionnaire was also observed at month 6 (P < 0.05 for each variable). CONCLUSION: Our results support a beneficial effect of the anti-TNF-α blockade on the mechanisms associated with accelerated atherogenesis in patients with psoriasis.

Relationship of leptin with adiposity and inflammation and resistin with disease severity in psoriatic patients undergoing anti-TNF-alpha therapy.

BACKGROUND: Altered secretion patterns of proinflammatory adipokines may influence the increased risk of cardiovascular mortality observed in patients with chronic inflammatory diseases. OBJECTIVE: To determine whether two adipokines, leptin and resistin, correlate with metabolic syndrome features and disease severity in psoriatic patients who underwent anti-TNF-α therapy. METHODS: Prospective study of consecutive non-diabetic patients with moderate-to-severe psoriasis who completed 6 months of therapy with anti-TNF-α- adalimumab. Patients with kidney disease, hypertension or body mass index ≥35 Kg/m(2) were excluded. Metabolic and clinical evaluation was performed at the onset of anti-TNF-α treatment and at month 6. RESULTS: Twenty-nine patients were assessed. A correlation between adiposity and leptin was observed (waist circumference and leptin levels after 6 months of therapy: r = 0.43; P = 0.030). Leptin concentration also correlated with blood pressure before adalimumab onset (systolic: r = 0.48; P = 0.013 and diastolic blood pressure: r = 0.50; P = 0.010 ). A marginally significant negative correlation between insulin sensitivity (QUICKI) and leptin levels was also observed. CRP levels correlated with leptin prior to the onset of adalimumab (r = 0.45; P = 0.020) and with resistin both before (r = 0.45; P = 0.020) and after 6 months of therapy (r = 0.55; P = 0.004). A positive association between parameters of disease activity such as BSA (r = 0.60; P = 0.001) and PASI (r = 0.63; P = 0.001) prior to the onset of adalimumab therapy and resistin concentrations was also disclosed. No significant changes in leptin and resistin concentrations following the 6-month treatment with adalimumab were seen. CONCLUSION: In patients with moderate-to-severe psoriasis leptin correlates with metabolic syndrome features and inflammation whereas resistin correlate with inflammation and disease severity.

Influence of the IL17A locus in giant cell arteritis susceptibility.

OBJECTIVE: Different lines of evidence have highlighted the role of IL-17A in the inflammatory process occurring in giant cell arteritis (GCA). The aim of the present study was to assess whether the IL17A locus influences GCA susceptibility and its clinical subphenotypes. METHODS: We carried out a large meta-analysis including a total of 1266 biopsy-proven GCA patients and 3779 healthy controls from four European populations (Spain, Italy, Germany and Norway). Five IL17A polymorphisms (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909) were selected by tagging and genotyped using TaqMan assays. Allelic combination and dependency tests were also performed. RESULTS: In the pooled analysis, two of the five analysed polymorphisms showed evidence of association with GCA (rs2275913: PMH=1.85E-03, OR=1.17 (1.06-1.29); rs7747909: PMH=8.49E-03, OR=1.15 (1.04-1.27)). A clear trend of association was also found for the rs4711998 variant (PMH=0.059, OR=1.11 (1.00-1.23)). An independent effect of rs2275913 and rs4711998 was evident by conditional regression analysis. In addition, the haplotype harbouring the risk alleles better explained the observed association than the polymorphisms independently (likelihood p value <10(-05)). CONCLUSIONS: Polymorphisms within the IL17A locus show a novel association with GCA. This finding supports the relevant role of the Th17 cells in this vasculitis pathophysiology.

Assessment of aortitis by semiquantitative analysis of 180-min 18F-FDG PET/CT acquisition images.

PURPOSE: The aim of this study was to evaluate the contribution of semiquantitative analysis of 180-min (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT images for the assessment of aortitis in cases of suspected large vessel vasculitis (LVV) and to establish a threshold index for application in the clinical setting. METHODS: This prospective study included 43 patients (mean age 67.5 ± 12.9 years) with suspicion of LVV (25 with a final diagnosis of aortitis). (18)F-FDG PET/CT scan was acquired 180 min after injection of 7 MBq/kg of (18)F-FDG. A semiquantitative analysis was performed calculating the aortic wall maximum standardized uptake value (SUVmax) (T), the lumen SUVmax (B) and the target to background ratio (TBR). These results were also compared with those obtained in a control population. RESULTS: The mean aortic wall SUVmax was 2.00 ± 0.62 for patients with aortitis and 1.45 ± 0.31 for patients without aortitis (p < 0.0001). The TBR was 1.66 ± 0.26 for patients with aortitis and 1.24 ± 0.08 for patients without aortitis (p < 0.0001). The differences were also statistically significant when the patients with aortitis and controls were compared. Receiver-operating characteristic (ROC) analysis revealed that the area under the curve was greater for the TBR than for the aortic wall SUVmax (0.997 vs 0.871). The highest sensitivity and specificity was obtained for a TBR of 1.34 (sensitivity 100%, specificity 94.4%). CONCLUSION: Semiquantitative analysis of PET/CT images acquired 180 min after (18)F-FDG injection and the TBR index of 1.34 show very high accuracy and, therefore, are strongly recommended for the diagnosis of aortitis in the clinical setting.

Cardiovascular risk assessment in rheumatoid arthritis: impact of the EULAR recommendations on a national calibrated score risk index.

OBJECTIVES: To evaluate the impact of the application of the EULAR task force recommendations in the cardiovascular (CV) risk assessment of rheumatoid arthritis (RA) patients according to a national calibrated SCORE. METHODS: Two hundred and one consecutive RA patients seen at the rheumatology outpatient clinics of the University Hospital 'San Cecilio', Granada, Southern Spain, were studied. Information on demographic, classic CV risk factors, history of CV events and disease clinical features were obtained. Both the systematic coronary risk evaluation (SCORE) risk index and the modified SCORE (mSCORE) following the EULAR recommendations were performed. RESULTS: Based on the classic CV risk factors the mean ± standard deviation SCORE was 2.2 ± 2.6 (median 2). Twenty-two (11%) patients were above the threshold of high risk for the Spanish population. Following the EULAR recommendations 52 of the 124 patients (41.93%) initially classified as having intermediate risk were reclassified as having high CV risk. Therefore, the mean mSCORE was 3.3 ± 4 (median 3) and, due to this, 74 (36.8%) patients were above the threshold of high CV risk for the Spanish population. As expected, patients who had experienced CV events were older, had more CV risk factors and higher mSCORE than those without CV events. CONCLUSIONS: These observations support the claim that the mSCORE should be specifically adapted to the population to be assessed. However, the use of additional tools should be considered in an attempt to fully identify high-risk RA patients.

Anti-TNF-α therapy in the management of severe neurosarcoidosis: a report of five cases from a single centre and literature review.

Neurologic manifestations are found in 5-15 % of patients with sarcoidosis. This granulomatous disease may affect any part of the peripheral or the central nervous system, being potentially severe and difficult to treat. Corticosteroids are the cornerstone of therapy in sarcoidosis. However, some patients become resistant or experience side effects to corticosteroids. In these patients, second line therapies including immunosuppressive drugs such as methotrexate, azathioprine, mycophenolate, cyclophosphamide and leflunomide have been used. Anti-TNF-α drugs have been proposed as a therapeutic option for those who are refractory to immunosuppressive drugs or initially in cases of severe sarcoidosis. We report on 5 patients with neurosarcoidosis treated with anti-TNF-α drugs in our center. A literature review of patients with neurosarcoidosis treated with anti-TNF-α drugs was conducted. In our series successful response to anti-TNF-α therapy was achieved. However, the high frequency of relapses following anti-TNF-α discontinuation makes necessary a close follow-up of these patients when the biologic agent is stopped.

Gelsolin levels are decreased in ankylosing spondylitis patients undergoing anti-TNF-alpha therapy.

OBJECTIVES: To determine whether circulating gelsolin (GSN) levels in patients with ankylosing spondylitis (AS) undergoing TNF-α antagonist-infliximab-therapy are altered compared with controls and to establish whether disease activity, systemic inflammation and metabolic syndrome are potential determinants of circulating GSN levels in these patients. METHODS: We assessed GSN serum concentrations in a series of 30 non-diabetic AS patients without cardiovascular (CV) disease undergoing TNF-α antagonist-infliximab therapy and 48 matched controls. GSN levels were measured immediately before and after an infliximab infusion. Correlations of GSN serum levels with disease activity, systemic inflammation and metabolic syndrome were assessed. Potential changes in GSN concentration following an infusion of anti-TNF-α monoclonal antibody-infliximab were also analysed. RESULTS: Although at the time of the study AS patients undergoing anti-TNF-α therapy had adequate control of the disease (mean BASDAI 2.94), they showed lower GSN serum levels than healthy controls (mean±SD: 38660.42±23624.6 ng/ml versus 68975.43±31246.79 ng/ml; p<0.0001). When AS patients were stratified according to sex, we observed that GSN levels were significantly lower in men than in women (p=0.032). However, no differences in GSN levels according to the specific clinical features of the disease were seen. No association was found between GSN concentration and adipokines or biomarkers of endothelial cell activation. However, correlation between basal GSN levels and insulin resistance was observed. A single infliximab infusion did not lead to significant changes in GSN levels. CONCLUSIONS: GSN concentration is reduced in AS patients undergoing periodical anti-TNF-α therapy and low disease activity. Potential association with some metabolic syndrome features seems to exist.

Correlation between two biomarkers of atherosclerosis, osteopontin and angiopoietin-2, in non-diabetic ankylosing spondylitis patients undergoing TNF-α antagonist therapy.

OBJECTIVES: To determine whether circulating osteopontin (OPN) levels in patients with ankylosing spondylitis (AS) undergoing TNF-α antagonist-infliximab-therapy are increased compared with controls and to establish whether disease activity, systemic inflammation, metabolic syndrome, adipokines and biomarkers of atherosclerosis are potential determinants of circulating OPN levels in these patients. METHODS: We assessed OPN serum concentrations in a series of 30 non-diabetic AS patients without cardiovascular disease undergoing TNF-α antagonist-infliximab therapy and 48 matched controls. OPN levels were measured immediately before and after an infliximab infusion, at time 0 and at time 120 minutes respectively. Correlations of OPN serum levels with clinical features, disease activity, systemic inflammation, metabolic syndrome and several biomarkers of atherosclerosis were assessed. Potential changes in OPN concentration following an infusion of anti-TNF-α monoclonal antibody-infliximab were also analysed. RESULTS: At the time of the study AS patients undergoing anti-TNF-α therapy had low disease activity (mean BASDAI 2.94) and they showed similar OPN serum levels to healthy controls. No differences in OPN levels according to the specific clinical features of the disease were seen. Also, no correlation between OPN concentration and insulin resistance and adipokines was observed. However, a positive correlation between OPN and angiopoietin-2 (Angpt-2) serum levels was found (r=0.397; p=0.04). In addition, a single infliximab infusion led to a marginal statistically significant reduction in OPN levels (24112.19±14608.73 pg/ml at time 0 versus 21806.62±11390.83 pg/ml at time 120'; p=0.05). CONCLUSIONS: OPN and Angpt-2 serum levels are correlated in non-diabetic AS patients undergoing TNF-α antagonist therapy.

No evidence of association between functional polymorphisms located within IL6R and IL6ST genes and Henoch-Schönlein purpura.

Henoch-Schönlein purpura (HSP) is the most common type of primary small-sized blood vessel vasculitis in children and an uncommon condition in adults. Interleukin (IL)-6 is a proinflammatory cytokine whose effect is controlled by the IL-6 receptor (IL-6R). IL-6 transducer (IL-6ST/gp130) is the signal-transducing subunit of the IL-6R. Two hundred and eighty five Spanish HSP patients and 877 sex and ethnically matched controls were genotyped for the IL6R rs2228145 and IL6ST/gp130 rs2228044 functional polymorphisms. No significant differences in the genotype and allele frequencies between HSP patients and controls were observed. Moreover, there were no differences between HSP patients according to the age at disease onset, presence of nephritis or gastrointestinal manifestations. Our results do not confirm association of IL6R rs2228145 and IL6ST/gp130 rs2228044 polymorphisms with HSP.