[Show abstract][Hide abstract] ABSTRACT: Introduction: To determine whether the PTPN22 (protein tyrosine phosphatase nonreceptor 22)/CSK (c-src tyrosine kinase) pathway is implicated in the susceptibility and clinical heterogeneity of Henoch-Schönlein purpura (HSP) in the largest series of Caucasian HSP patients ever assessed for genetic studies. Methods: A set of 329 Spanish patients diagnosed with HSP fulfilling the American College of Rheumatology and the Michel et al. classification criteria and 515 sex and ethnically matched controls were recruited in this study. Two well-known CSK (CSK rs34933034 and CSK rs1378942) and two functional PTPN22 (PTPN22 rs2476601 (R620W) and PTPN22 rs33996649 (R263Q)) polymorphisms, previously associated with autoimmunity, were genotyped with TaqMan single nucleotide polymorphism (SNP) genotyping assays. Results: No significant differences in the genotype and allele frequencies between HSP patients and controls were observed when the CSK rs34933034, CSK rs1378942, PTPN22 rs2476601 (R620W) and PTPN22 rs33996649 (R263Q) polymorphisms were analyzed independently. In keeping with this observation, no significant differences were found when we assessed these polymorphisms combined conforming haplotypes. In addition, there were no differences in the allele or genotype frequencies when HSP patients were stratified according the age at disease onset, sex, presence of arthralgia/arthritis, nephritis or gastrointestinal manifestations. Conclusions: Our results do not support association between PTPN22/CSK and HSP.
[Show abstract][Hide abstract] ABSTRACT: Objectives:
To determine whether the interleukin-33 (IL-33)-interleukin-1 receptor like 1 (IL-1RL1) signaling pathway is implicated in the risk of subclinical atherosclerosis in patients with rheumatoid arthritis (RA).
A total of 576 Spanish RA patients from Northern Spain were genotyped for 6 well-known IL33-IL1RL1 polymorphisms (IL33 rs3939286, IL33 rs7025417, IL33 rs7044343, IL1RL1 rs2058660, IL1RL1 rs2310173 and IL1RL1 rs13015714) by TaqMan genotyping assay. The presence of subclinical atherosclerosis was determined by the assessment of carotid intima-media thickness (cIMT) by carotid ultrasound (US).
RA patients carrying the TT genotype of the IL33 rs3939286 polymorphism had lower cIMT values than those homozygous for the CC genotype (mean ± standard deviation (SD): 0.71 ± 0.14 mm versus 0.76 ± 0.16 mm, respectively) while patients carrying the CT genotype had intermediate cIMT values (mean ± SD: 0.73 ± 0.17 mm). Moreover, RA patients carrying the mutant allele T of the IL33 rs3939286 polymorphism exhibited significantly lower cIMT values than those carrying the wild allele C (mean ± SD: 0.72 ± 0.16 mm versus 0.75 ± 0.18 mm respectively; p = 0.04). The association of both genotype and allele frequencies of IL33 rs3939286 and cIMT levels remained statistically significant after adjustment for sex, age at the time of US study, follow-up and center (p = 0.006 and p = 0.0023, respectively), evidencing that the potential effect conferred by IL33 rs3939286 may be independent of confounder factors. No association with other IL33-IL1RL1 genetic variants was observed.
In conclusion, our results may suggest a potential protective effect of the IL33 rs3939286 allele T in the risk of subclinical atherosclerosis in patients with RA.
PLoS ONE 11/2015; 10(11):e0143153. DOI:10.1371/journal.pone.0143153 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Endothelial dysfunction can be detected by the presence of elevated levels of biomarkers of endothelial cell activation. In this study, we aimed to establish whether correlations of these biomarkers with characteristics of patients with ankylosing spondylitis (AS) exist. We also studied the effect of anti-TNF-α therapy on these biomarkers. Serum sE-selectin, MCP-1 and sVCAM-1 levels were measured by ELISA in 30 non-diabetic AS patients undergoing anti-TNF-α therapy, immediately before and after an infusion of infliximab. Correlations of these biomarkers with clinical features, systemic inflammation, metabolic syndrome and other serum and plasma biomarkers of cardiovascular risk were studied. Potential changes in the concentration of these biomarkers following an infliximab infusion were also assessed. sE-selectin showed a positive correlation with CRP (p = 0.02) and with other endothelial cell activation biomarkers such as sVCAM-1 (p = 0.019) and apelin (p = 0.008). sVCAM-1 negatively correlated with BMI (p = 0.018), diastolic blood pressure (p = 0.008) and serum glucose (p = 0.04). sVCAM-1 also showed a positive correlation with VAS spinal pain (p = 0.014) and apelin (p < 0.001). MCP-1 had a negative correlation with LDL cholesterol (p = 0.026) and ESR (p = 0.017). Patients with hip involvement and synovitis and/or enthesitis in other peripheral joints showed higher levels of MCP-1 (p = 0.004 and 0.02, respectively). A single infliximab infusion led to a significant reduction in sE-selectin (p = 0.0015) and sVCAM-1 (p = 0.04). Endothelial dysfunction correlates with inflammation and metabolic syndrome features in patients with AS. A beneficial effect of the anti-TNF-α blockade on endothelial dysfunction, manifested by a reduction in levels of biomarkers of endothelial cell activation, was observed.
Rheumatology International 07/2015; 74(Suppl 2). DOI:10.1007/s00296-015-3314-1 · 1.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine whether the human leukocyte antigen (HLA) B alleles are implicated in the susceptibility to Henoch-Schönlein purpura (HSP) in the largest series of Caucasian HSP patients ever assessed for genetic studies.
The study population was composed of 349 Spanish patients diagnosed with HSP fulfilling the American College of Rheumatology and the Michel et al. classification criteria, and 335 sex and ethnically matched controls. HLA-B phenotypes were determined by sequencing-based typing (SBT) and analyzed by chi-square or Fisher exact test.
A statistically significant increase of HLA-B*41:02 allele in HSP patients when compared with controls was found (8.3% versus 1.5% respectively; p = 0.0001; OR (odds ratio) =5.76 [2.15-19.3]). These results remained statistically significant after adjusting for Bonferroni correction (p = 0.0028). An internal validation also confirmed the susceptibility effect on HSP associated with HLA-B*41:02 (OR = 5.70 [1.98-16.44]). Since a former study described an association between HLA-DRB1*01:03 and HSP susceptibility, we also evaluated the implication of HLA-B*41:02 independently of HLA-DRB1*01:03. Interestingly, the association remained statistically significant (p = 0.0004, OR = 4.97 [1.8-16.9]). No HLA-B association with specific HSP clinical features was found.
Our study indicates that HLA-B*41:02 is associated with the susceptibility to HSP in Spanish patients irrespective of HLA-DRB1 status.
[Show abstract][Hide abstract] ABSTRACT: Like rheumatoid arthritis, ankylosing spondylitis (AS) is also an inflammatory disease associated with accelerated atherosclerosis and the presence of metabolic syndrome (MeS) features. AS patients often display osteoporosis as well as new bone formation. Insulin-like growth factor 1 (IGF-1) is a protein involved in both inflammation and bone metabolism. In the present study we assessed whether disease activity, systemic inflammation, MeS features, adipokines, and biomarkers of endothelial activation were associated with IGF-1 and insulin-like growth factor binding protein-3 (IGFBP-3) levels in a series of 30 nondiabetic AS patients without CV disease undergoing TNF-α antagonist-infliximab therapy. All determinations were made in the fasting state, immediately before an infliximab infusion. Although no association of IGF-1 and IGFBP-3 levels with angiopoietin-2 or osteopontin was found, an inverse correlation between IGF-1 levels and asymmetric dimethylarginine (ADMA), an endogenous endothelial nitric oxide synthase inhibitor that impairs nitric oxide production and secretion promoting endothelial dysfunction, was found (r = -0.397; P = 0.04). However, no significant association was found between IGF-1 and IGFBP-3 levels and disease activity, systemic inflammation, metabolic syndrome features, or adipokines. In conclusion, in nondiabetic patients with AS undergoing periodic anti-TNF-α therapy, IGF-1 and ADMA are inversely correlated.
BioMed Research International 09/2014; 2014:671061. DOI:10.1155/2014/671061 · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives:
Osteoprotegerin (OPG) has been associated with increased risk and severity of atherosclerotic disease in the general population. Since ankylosing spondylitis (AS) is a chronic inflammatory disease associated with accelerated atherosclerosis, we aimed to assess whether OPG levels correlate with disease activity, systemic inflammation, metabolic syndrome, adipokines and biomarkers of endothelial cell activation in patients with AS undergoing TNF-α antagonist therapy.
We assessed OPG plasma concentration in 30 non-diabetic AS patients without cardiovascular disease undergoing TNF-α antagonist-infliximab therapy. OPG levels were measured immediately before and after an infliximab infusion. Correlations of OPG levels with disease activity, clinical characteristics, systemic inflammation, metabolic syndrome features, adipokines and biomarkers of endothelial activation were assessed. Changes in OPG concentration following an infusion of anti-TNF-α monoclonal antibody-infliximab were also analysed.
We found a positive correlation between OPG levels and markers of disease activity such as BASDAI and VAS spinal pain (r=0.497, p=0.01; r=0.390; p=0.04, respectively). No differences in OPG levels according to specific clinical features of the disease were seen. An inverse correlation between OPG levels and total cholesterol and LDL-cholesterol was also found (r=-0.451; p=0.02 and r=-0.411; p=0.03, respectively). A correlation between OPG and asymmetric dimethylarginine, a biomarker of endothelial cell activation, was also disclosed (r=0.533; p=0.01). No correlation between OPG level and insulin resistance was observed. An infliximab infusion did not lead to a significant reduction in OPG levels.
OPG shows a correlation with markers of disease activity and endothelial activation in non-diabetic ankylosing spondylitis patients undergoing TNF-α antagonist therapy.
Clinical and experimental rheumatology 09/2014; 32(5). · 2.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction
Rheumatoid arthritis is an inflammatory disease with high incidence of cardiovascular disease due to accelerated atherosclerosis. Osteoprotegerin (OPG) has been associated with increased risk of atherosclerotic disease in the general population. Several polymorphisms in the OPG gene with functional effects on cardiovascular disease in non-rheumatic individuals have been described. Therefore, we aimed to analyze the effect of three of these functional OPG polymorphisms on the risk of cardiovascular disease in a large and well-characterized cohort of Spanish patients with rheumatoid arthritis.
Three OPG gene variants (rs3134063, rs2073618 and rs3134069) were genotyped by TaqMan assays in 2027 Spanish patients with rheumatoid arthritis. Anti-cyclic citrullinated peptide (anti-CCP) antibody testing was positive in 997 of 1714 tested. Also, 18.3% of the whole series had experienced cardiovascular events, including 5.4% with cerebrovascular accidents. The relationship between OPG variants and cardiovascular events was assessed using Cox regression.
No association between OPG gene variants and cardiovascular disease was observed in the whole group of rheumatoid arthritis patients or in anti-CCP positive patients. Nevertheless, a protective effect of CGA haplotype on the risk of cardiovascular disease in general, and specifically in the risk of cerebrovascular complications after adjusting for sex, age at disease diagnosis and traditional cardiovascular risk factors was disclosed in anti-CCP negative patients (HR = 0.54; 95%CI: 0.31–0.95; p = 0.032 and HR = 0.17; 95%CI: 0.04–0.78; p = 0.022, respectively).
Our results indicate a protective effect of the OPG CGA haplotype on cardiovascular risk, mainly due to a protective effect against cerebrovascular events in anti-CCP negative rheumatoid arthritis patients.
PLoS ONE 09/2014; 9(9):e106823. DOI:10.1371/journal.pone.0106823 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction
Rheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis and increased cardiovascular (CV) disease risk. Interferon regulatory factor 5 (IRF5) is a regulator of type I interferon induction. Recently, researchers have described an association between multiple single-nucleotide polymorphisms of the IRF5 gene and some rheumatic disorders. In this study, we aimed to evaluate whether three different haplotype blocks within the IRF5 locus which have been shown to alter the protein function are involved in the risk of CV events occurring in Spanish RA patients.
Three IRF5 polymorphisms (rs2004640, rs2070197 and rs10954213) representative of each haplotype group were genotyped by performing TaqMan assays using a 7900HT Fast Real-Time PCR System with tissue from a total of 2,137 Spanish patients diagnosed with RA. Among them, 390 (18.2%) had experienced CV events. The relationship of IRF5 genotypes and haplotypes to CV events was tested using Cox regression.
Male sex, age at RA diagnosis and most traditional risk factors (hypertension, dyslipidemia and smoking habit) were associated with increased risk for CV events in the RA population. Interestingly, a protective effect of both IRF5 rs2004640 GG and IRF5 rs10954213 GG genotypes against the risk for CV events after adjusting the results for sex, age at RA diagnosis and traditional CV disease risk factors was observed (hazard ratio (HR) = 0.6, 95% confidence interval (CI) = 0.38 to 0.92, P = 0.02; and HR = 0.58, 95% CI = 0.36 to 0.95, P = 0.03, respectively). Moreover, we detected a protective effect of the GTG haplotype against the risk for CV events after adjusting the results for potential confounding factors (HR = 0.72, 95% CI = 0.56 to 0.93, P = 0.012).
Our results reveal that IRF5 gene variants are associated with risk of CV events in patients with RA.
[Show abstract][Hide abstract] ABSTRACT: Background Rheumatoid arthritis (RA) is an autoimmune inflammatory disease associated with accelerated atherosclerosis and increased cardiovascular (CV) disease. A genetic component has been implicated in atherosclerosis. Recently, the ABO rs579459, PPAP2B rs17114036, ADAMTS7 rs3825807 polymorphisms have been associated with coronary artery disease  and the PIK3CG rs17398575, EDNRA rs1878406 variants with carotid plaques in general population .
Objectives We aimed to determine the potential role of these 5 polymorphisms and cIMT, presence/absence of carotid plaques and CV events in RA.
Methods Polymorphisms were analyzed in 2140 Spanish RA patients by TaqMan assays. Subclinical aterosclerosis was determined by carotid ultrasonography (US) in 620 patients.
Results No statistical significant differences were observed when the ABO rs579459, PPAP2B rs17114036 and ADAMTS7 rs3825807 polymorphisms and CV events were compared. It was also the case when PIK3CG rs17398575 and EDNRA rs1878406 polymorphisms and cIMT and carotid plaques were analyzed.
Conclusions Our results do not confirm an association of these 5 polymorphisms and subclinical atherosclerosis and CV in RA.
Acknowledgements This study was supported by European Union FEDER funds and “Fondo de Investigaciόn Sanitaria” (PI06/0024, PS09/00748 and PI12/00060) from `Instituto de Salud Carlos III” (ISCIII, Spain). It was also partially supported by RETICS Programs RD12/0009/0013 and RD12/0009/0004 (RIER) from ISCIII and by grants from the European IMI BTCure Program. RLM is a recipient of a Sara Borrell postdoctoral fellowship from ISCIII (CD12/00425). FG and BU are supported by funds from the RETICS Program (RIER). MGB is a beneficiary of a grant from Fundaciόn Española de Reumatología (FER).
Disclosure of Interest None declared
[Show abstract][Hide abstract] ABSTRACT: Objective:
TRAIL is a potential biomarker of cardiovascular (CV) disease. Ankylosing spondylitis (AS) is a chronic inflammatory disease associated with metabolic syndrome (MeS) and accelerated atherosclerosis. We assessed whether disease activity, systemic inflammation, and MeS features were associated with circulating TRAIL levels in AS patients undergoing TNF-α antagonist infliximab therapy and if infliximab infusion modified TRAIL levels.
We measured TRAIL serum levels in 30 nondiabetic AS patients without CV disease undergoing anti-TNF-α therapy, immediately before and after an infliximab infusion, and in 48 matched controls. Correlations of TRAIL levels with disease activity, systemic inflammation and MeS features, adipokines, and biomarkers of endothelial activation were evaluated. Changes in TRAIL levels following anti-TNF-α infusion were analyzed.
TRAIL levels were higher in AS patients than controls. TRAIL levels displayed an inverse correlation with total and LDL cholesterol. We observed an inverse correlation with QUICKI and a marginal association with HOMA-IR. We also found an inverse correlation with resistin and a marginal association with apelin and OPN. Anti-TNF-α infusion did not change TRAIL levels after 120'.
Elevated TRAIL levels in AS patients may be the result of a compensatory mechanism to reduce CV risk in these patients.
Mediators of Inflammation 05/2014; 2014(4):798060. DOI:10.1155/2014/798060 · 3.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Xq28 region, containing IRAK and MECP2, represent a common susceptibility locus for a high number of autoimmune diseases. Our aim in the present study was to evaluate the influence of the IRAK1 and MECP2 autoimmunity-associated genetic variants in the giant cell arteritis (GCA) susceptibility and its clinical subphenotypes.
We analysed a total of 627 female biopsy-proven GCA patients and 1,520 female healthy controls of Spanish Caucasian origin. Two polymorphisms, rs1059702 and rs17345, located at IRAK1 and MECP2, respectively, were genotyped using TaqMan® allelic discrimination assays.
No association with any of the analysed polymorphisms was evident when genotype and allele frequencies were compared between GCA patients and controls (rs1059702: allelic p-value=0.699, OR=0.96, CI 95% 0.80-1.17; rs17435: allelic p-value=0.994, OR=1.00, CI 95% 0.84-1.19). Likewise, the subphenotype analysis yield similar negative results.
We have assessed for the first time the possible role of IRAK1 and MECP2 autoimmune disease-associated polymorphisms in GCA. Our data suggest that IRAK1 rs1059702 and MECP2 rs17435 genetic variants do not play a significant role in GCA susceptibility or severity.
[Show abstract][Hide abstract] ABSTRACT: Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease associated with accelerated atherosclerosis and increased risk of cardiovascular (CV) disease. AS patients also display a high prevalence of features clustered under the name of metabolic syndrome (MeS). Anti-TNF- α therapy was found to be effective to treat AS patients by suppressing inflammation and also improving endothelial function. Previously, it was demonstrated that a short infusion of anti-TNF- α monoclonal antibodyinfliximab induced a rapid and dramatic reduction in serum insulin levels and insulin resistance along with a rapid improvement of insulin sensitivity in nondiabetic AS patients. The role of adipokines, MeS-related biomarkers and biomarkers of endothelial cell activation and inflammation seem to be relevant in different chronic inflammatory diseases. However, its implication in AS has not been fully established. Therefore, in this review we summarize the recent advances in the study of the involvement of these molecules in CV disease or MeS in AS. The assessment of adipokines and biomarkers of endothelial cell activation and MeS may be of potential relevance in the stratification of the CV risk of patients with AS.
[Show abstract][Hide abstract] ABSTRACT: Osteoprotegerin (OPG) may contribute to the link between systemic inflammation and increased cardiovascular risk. We investigated the relationship of OPG concentrations with endothelial activation and carotid atherosclerosis in rheumatoid arthritis (RA).
OPG concentrations and those of endothelial activation molecules were measured by using ELISA in 34 patients who were treated with infliximab (IFX), both immediately before and after an IFX infusion. Carotid intima-media thickness (CIMT) and plaque were determined by ultrasound in 27 of the study participants.
Median (interquartile range) OPG concentrations decreased from 4.8 pmol/l (2.8-6.5) to 4.4 pmol/l (2.9-6.1; p = 0.04) upon IFX infusion. Baseline OPG concentrations were inversely associated with those of total and low-density lipoprotein (LDL) cholesterol (partial R = -0.50, p = 0.004, and R = -0.48, p = 0.007, respectively). Prior to IFX administration, OPG concentrations were associated with those of intercellular adhesion molecule (ICAM)-1 (partial R = 0.34, p = 0.05), CIMT (partial R = 0.51 to 0.52, p < 0.009), and plaque (OR = 1.52, 95% CI 1.01-2.29 to OR = 1.61, 95% CI 1.03-2.51; p < 0.04), independent of conventional risk factors and C-reactive protein concentrations or disease activity. Except for the OPG concentrations-plaque association (p = 0.09), these relationships remained significant subsequent to IFX administration (p < 0.05). Reductions in OPG levels related to those in vascular cell adhesion molecule (VCAM)-1 concentrations (partial R = 0.35, p = 0.04) and had borderline significance (p = 0.09) with those in ICAM-1 (partial R = 0.29) concentrations.
OPG concentrations are independently associated with endothelial activation and carotid atherosclerosis in RA. Reductions in OPG concentrations upon IFX administration are associated with decreased endothelial activation. OPG may be involved in increased cardiovascular disease risk and may improve its stratification in patients with RA.
The Journal of Rheumatology 02/2014; 41(3). DOI:10.3899/jrheum.131037 · 3.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with high risk of cardiovascular (CV) disease (1). Besides classic CV risk factors, “high-grade” systemic inflammation and immune dysregulation play a crucial role in the development of accelerated atherosclerosis observed in RA (2-5). IFN-γ is a pleiotropic soluble cytokine with antiviral and anti-tumor properties. This cytokine is found in RA patients’ synovium and synovial fluid (6), and polymorphisms within its gene sequence may be biologically plausible candidates for influencing the incidence and severity of RA (7).
Objectives In this study we assessed the potential association of the IFNG functional gene variant rs2430561 with CV disease in RA patients.
Methods 1406 patientsfulfilling the 1987 ACR classification criteria for RA were genotyped for the IFNG (rs2430561, +874A/T) polymorphism by ARMS-PCR method followed by gel electrophoresis analysis. Patients were stratified according to the presence of CV events or not. Logistic regression models to explain the presence of CV disease according to the IFNG rs2430561allele distribution were performed. The potential influence of this variant in the development of subclinical atherosclerosis was also analyzed in a subgroup of patients with no history of CV events to determine endothelial function (Flow-Mediated endothelium-dependent, FMD) (n=128) and carotid artery intima-media thickness (IMT) (n=108), respectively.
Results Adjusted logistic regression model disclosed that presence of the minor allele T was associated with increased risk of suffering CV events in RA patients (p=0.022, OR 1.63 [95% CI 1.07-2.49]). This increased risk was also observed in the subgroup of patients with heart failure (p=0.025, OR 2.45 [95% CI 1.12-5.37]). Also, higher carotid IMT and lower FMD values were found in RA patients carrying IFNG rs2430561 variant allele T, although differences did not achieve statistical significance.
Conclusions IFNG rs2430561 (+874A/T) gene functional variant may influence the development of CV disease in patients with RA.
Acknowledgements Supported by two grants from Fondo de Investigaciones Sanitarias PI06-0024 and PS09/00748 (Spain). This work was partially supported by RETICS Program, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII), within the VI PN de I+D+i 2008-2011 (FEDER). MGB is a recipient of a grant from Fundaciόn Española de Reumatología (FER).
Disclosure of Interest None Declared
Annals of the Rheumatic Diseases 01/2014; 71(Suppl 3):476-476. DOI:10.1136/annrheumdis-2012-eular.2964 · 10.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background CD226 genetic variants have been associated with a number of autoimmune diseases.
Objectives The aim of this study was to investigate the potential implication of the CD226 loci in the susceptibility to and main clinical manifestations of giant cell arteritis (GCA).
Methods A Spanish Caucasian cohort of 455 patients diagnosed with biopsy-proven
GCA and 1414 healthy controls were included in the study. Three CD226 polymorphisms, rs727088, rs34794968 and rs763361, were genotyped using the TaqMan® allelic discrimination technology. PLINK software was used for the statistical analyses.
Results No significant association between the CD226 polymorphisms and susceptibility to GCA was found (rs727088: P=0.92, OR=1.01 CI 95% 0.86-1.18; rs34794968: P=0.61, OR=1.04 CI 95% 0.89-1.22; rs763361: P=0.88, OR=0.99 CI 95% 0.84-1.16). Similarly, when patients were stratified according to the specific clinical features of GCA such as polymyalgia rheumatica, visual ischemic manifestations or irreversible occlusive disease, no association was observed either between the case subgroups and the control set or between GCA patients with and without the specific features of the disease. Furthermore, the haplotype analysis revealed no significant association with the disease.
Conclusions Our results show that the CD226 gene does not play a relevant role in the susceptibility to GCA and clinical manifestations of this vasculitis.
Disclosure of Interest None Declared
Annals of the Rheumatic Diseases 01/2014; 71(Suppl 3):637-637. DOI:10.1136/annrheumdis-2012-eular.07 · 10.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
Clinical and experimental rheumatology 12/2013; 32(2). · 2.72 Impact Factor