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ID PMID Title PublicationDate abstract
20556817 Efficacy and safety of a selective estrogen receptor β agonist, ERB-041, in patients with 2010 Nov OBJECTIVE: Selective estrogen receptor β (ERβ) agonists have demonstrated relevant antiinflammatory effects in different animal models. This study aimed to compare the efficacy and safety of one of these agonists, ERB-041, in subjects with rheumatoid arthritis (RA). METHODS: A total of 291 patients with active RA receiving stable doses of methotrexate were randomized to receive 5, 25, or 75 mg of ERB-041 or placebo for 12 weeks. The primary end point was the American College of Rheumatology 20% improvement criteria (ACR20) at 12 weeks. Secondary end points included the ACR 50% improvement criteria (ACR50) and the ACR 70% improvement criteria (ACR70) responses, health outcomes measures, C-reactive protein (CRP) levels, and potential exposure-response relationships. Medical history, physical examination, and laboratory values were obtained at screening, baseline, and weeks 2, 4, 8, and 12. RESULTS: No statistically significant difference for the ACR20 was found between the ERB-041 treatment and placebo groups (P = 0.518). Nor was a significant difference observed for ACR50 and ACR70 responses, health outcomes measures, CRP levels, and overall incidence of adverse events among all groups. Forty-four subjects (15.1%) discontinued the study and the rate of discontinuation was similar among the treatment groups. The most commonly reported treatment-emergent adverse events were headache (7.6%), nausea (6.2%), infection (4.8%), and bronchitis (4.1%). None of the adverse events was considered treatment related. CONCLUSION: Although well tolerated and safe, ERB-041 failed to demonstrate antiinflammatory efficacy in RA patients, despite evidence of strong activity in preclinical arthritis models. These results suggest that selective ERβ agonists would not have effects on regulating inflammatory response in RA. Nevertheless, further studies are warranted to establish their efficacy in inflammatory arthritis.
19966089 Tumour necrosis factor alpha -308G->A polymorphism is not associated with response to TNFa 2010 Jun BACKGROUND: There is a need for biomarkers that can predict anti-tumour necrosis factor (anti-TNF) treatment outcome in patients with rheumatoid arthritis (RA). Several studies have suggested that the rare A allele of the tumour necrosis factor alpha (TNFA) -308G-->A polymorphism could be associated with a poorer response to anti-TNF therapy. Nevertheless, these results remain controversial. OBJECTIVE: To determine by a meta-analysis whether the TNFA -308G-->A polymorphism is associated with response to anti-TNF treatment in patients with RA. METHODS: A bibliographic search identified studies in which the TNFA -308G-->A gene polymorphism was investigated in Caucasian patients with RA treated with anti-TNF agents. Complementary data were requested when the 28-joint count Disease Activity Score (DAS28) was not used as the primary outcome measure. Odds ratios (ORs) for response based on DAS28 and standardised mean difference (SMD) for mean improvement of DAS28 were calculated to assess the potential association between TNFA -308 genotypes and response to anti-TNF agents. RESULTS: The bibliographic search yielded 12 studies that met the inclusion criteria, which were supplemented with the data from a large Dutch cohort (n=426). The OR based on the 12 studies including 1721 patients was 1.24 (95% CI 0.98 to 1.56) and the SMD based on 11 studies including 2579 patients was -0.18 (95% CI -0.36 to 0.1). Subgroup analysis based on the two classes of anti-TNF agents did not demonstrate any association between TNFA -308 genotypes and anti-TNF treatment outcome. CONCLUSION: According to this meta-analysis, the TNFA -308 polymorphism is not a predictor of the clinical response to anti-TNF treatment in RA.
19771491 A meta-analysis of the efficacy and safety of using infliximab for the treatment of rheuma 2009 Dec Infliximab is a chimeric monoclonal antibody. Published studies indicate that its use in patients with rheumatoid arthritis can be efficient in providing long-term benefits. The aim of this study is to evaluate the efficacy and safety of using infliximab for the treatment of rheumatoid arthritis. A systematic review was performed to search for randomized clinical trials that compared intravenous administration of 3 mg/kg body weight infliximab or placebo in patients concomitantly using methotrexate. Only studies of moderate or high quality were included. A meta-analysis was conducted to assess the efficacy (based on changes of American College of Rheumatology (ACR) criteria) and the safety (based on serious adverse events, serious infections, malignancy, and deaths) of infliximab use. Withdrawals due to adverse events or lack of efficacy were also evaluated in both infliximab-treated and control groups. Seven trials met the inclusion criteria, comprising 2,129 patients. In the efficacy meta-analysis, a greater number of infliximab-treated patients relative to those in the placebo group achieved ACR20, ACR50, and ACR70 values from 14 weeks to 2 years of treatment. For safety analysis, there were no statistically significant differences between the groups. Withdrawals due to adverse events were higher in the infliximab group relative to the placebo group, and withdrawals due to lack of efficacy were higher in the placebo group relative to the infliximab-treated group. This meta-analysis shows a higher efficacy of infliximab relative to placebo without significant safety differences between the infliximab-treated and control groups.
19822062 Treatment of rheumatoid arthritis and ankylosing spondylitis. 2009 Jul The treatment of the two most frequent inflammatory rheumatic diseases rheumatoid arthritis (RA) and ankylosing spondylitis (AS) has some similarities but in total more differences. Thus, therapy with non-steroidal anti-inflammatory agents (NSAIDs), conventional disease modifying anti-rheumatic drugs (DMARDs) and biologic agents has a different role in the management and different efficacy in AS and RA. This implies signs and symptoms, function, and structural damage. This is in part due to the different pathogenesis: (i) while the synovium is an important target in RA it is rather the bone in AS and (ii) while the pathology in RA is rather osteodestructive to cartilage and bone presenting with erosions, it is predominantly osteoproliferative in AS as indicated by syndesmophytes and ankylosis. Biologic agents targeting tumor necrosis factor (TNF-alpha) work clinically well in both diseases but, while they clearly inhibit structural damage in RA, they do not seem to have much influence on new bone formation in AS. DMARDs are efficacious in RA but less so in AS. NSAIDs are efficacious in both RA and AS, but they are considered first line of therapy in AS while they are rather adjunctive agents in RA. In AS, NSAIDs, potentially especially coxibs, may even prevent new bone formation due to their inhibitory effect on cyclooxygenase-2.
20345981 A role for human endogenous retrovirus-K (HML-2) in rheumatoid arthritis: investigating me 2010 Jun Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections within the human genome. These molecular fossils draw parallels with present-day exogenous retroviruses and have been linked previously with immunopathology within rheumatoid arthritis (RA). Mechanisms of pathogenesis for HERV-K in RA such as molecular mimicry were investigated. To clarify a role for HERVs in RA, potential autoantigens implicated in autoimmunity were scanned for sequence identity with retroviral epitopes. Short retroviral peptides modelling shared epitopes were synthesized, to survey anti-serum of RA patients and disease controls. A novel real-time polymerase chain reaction (PCR) assay was also developed to quantify accurately levels of HERV-K (HML-2) gag expression, relative to normalized housekeeping gene expression. Both serological and molecular assays showed significant increases in HERV-K (HML-2) gag activity in RA patients, compared to disease controls. The real-time PCR assay identified significant up-regulation in HERV-K mRNA levels in RA patients compared to inflammatory and healthy controls. Exogenous viral protein expression and proinflammatory cytokines were also shown to exert modulatory effects over HERV-K (HML-2) transcription. From our data, it can be concluded that RA patients exhibited significantly elevated levels of HERV-K (HML-2) gag activity compared to controls. Additional factors influencing HERV activity within the synovium were also identified. The significant variation in RA patients, both serologically and transcriptionally, may be an indication that RA is an umbrella term for a number of separate disease entities, of which particular HERV polymorphisms may play a role in development.
19117247 Rheumatoid arthritis in UK primary care: incidence and prior morbidity. 2009 May OBJECTIVES: To estimate the incidence of rheumatoid arthritis (RA) in primary care and to investigate associations with consultation behaviour, risk factors, and comorbidities, using the UK General Practice Research Database (GPRD). METHODS: Subjects with a first-ever diagnosis of RA between 1 January 1996 and 31 December 1997 (n = 579) were identified from a cohort of 1 206 918 subjects aged 20-79 years without cancer. Controls from the same cohort were frequency-matched to the RA group by age, sex, and calendar year (n = 4234). Odds ratios (ORs) and 95% confidence intervals (CIs) of being diagnosed with RA in association with a range of factors were estimated using logistic regression analysis. RESULTS: RA incidence was 0.15 per 1000 person-years, was higher in women than in men, and increased with age in both sexes. Consultations and use of non-steroidal anti-inflammatory drugs (NSAIDs) prior to diagnosis were increased in subjects with RA. An increased risk of RA was observed in association with anaemia in the previous year (OR 2.63, 95% CI 1.54-4.48) and with smoking (1.33, 1.07-1.67). A decreased risk of RA was observed in association with infectious diseases (0.68, 0.50-0.94) and pregnancy in the previous year (0.22, 0.06-0.77), diabetes (0.45, 0.26-0.78), and hypertension (0.74, 0.57-0.94). We found no association with alcohol intake, obesity, or use of low-dose aspirin, oral contraceptives, or hormone replacement therapy (HRT). CONCLUSIONS: Smoking was identified as the only significant lifestyle-related risk factor for RA. Infection in the previous year was associated with a reduced likelihood of RA.
19267774 Is it possible to identify early predictors of the future cost of chronic arthritis? The V 2009 Feb This study was conducted to identify early predictors of the total cost of inflammatory arthritis (IA). One hundred and eighty patients affected by undifferentiated arthritis (UA) or rheumatoid arthritis (RA) were included in the French Very Early rheumatoid Arthritis (VErA) cohort between 1998 and 2001. Health economic data for 2003 were collected using a patient self-questionnaire. Results were analysed in terms of direct, indirect and total costs in 2003 euros (2003euro) for the population as a whole and in diagnostic subgroups. A payor perspective (the French National Health Insurance, in this case) was adopted. Multiple linear regression models were used to identify predictors of total cost from among the criteria assessed on recruitment. Results of the study showed that for the study population as a whole, the mean total cost was euro4700 per patient. The costs attributable to the RA and UA sub-groups were euro5928 and euro2424 per patient, respectively. In a univariate analysis, certain parameters were significantly correlated with a higher cost of illness. In the multivariate analysis, some of these parameters were further identified as being predictive of higher cost. Two strong significant, early predictors of total cost were identified: higher pain (P = 0.002) and the presence of rheumatoid factor (P = 0.004). In the RA sub-group, lower grip strength of the dominant hand (P = 0.039) was another predictor of the illness's subsequent economic impact. In conclusion, our data show that simple clinical and laboratory parameters can be used early in the course of IA to predict the condition's impact on healthcare budgets.
20470953 Medical imaging and radiographic analysis of the rheumatoid patient. 2010 Apr According to the Arthritis Foundation, approximately 1.3 million Americans have rheumatoid arthritis (RA), while an estimated 300,000 children are diagnosed with the disease each year. The disease is 2- to 4-times more common in women than in men and is least common in young men. Current practices in the treatment of RA center on the early detection of the various disease manifestations, specifically joint destruction. The goal of early detection is the implementation of disease-modifying drugs before articular destruction and deformity set in. Advancements in medical imaging have led to methods that facilitate earlier detection and beneficial treatment in the course of RA. Because standard radiographic interpretation assists with diagnosis of later-stage arthritis after articular destruction has occurred, magnetic resonance imaging has proven to be the most effective study for early signs of RA. Other imaging modalities such as ultrasonography and contrast-enhanced computed tomography have also been shown to detect early signs of RA. In conjunction with laboratory testing, these imaging modalities are essential for the early detection and subsequent treatment of RA. Pedal imaging is used by most rheumatologists to detect and monitor disease progression, and by most podiatric surgeons to help direct treatment and plan surgical intervention.
19347182 Simultaneous evaluation of in vivo glucocorticoid sensitivity and expression of glucocorti 2009 Feb OBJECTIVES: To analyze glucocorticoid (GC) sensitivity using intravenous very low dose dexamethasone suppression test (IV-VLD-DST) in patients with rheumatoid arthritis (RA) and its correlation with glucocorticoid receptor alpha-isoform (GRalpha) gene expression. METHODS: We evaluated 20 healthy controls and 32 RA patients with Health Assessment Questionnaire (HAQ) and Disease Activity Score 28 joints (DAS) scores and IV-VLD-DST and GRalpha expression in mononuclear cells. RESULTS: Basal cortisol and the percentage of cortisol reduction after IV-VLD-DST were lower in RA patients than in controls, whereas GRalpha expression was similar among groups. In the RA group there was an inverse correlation between GRalpha expression and the percentage of cortisol suppression that was not observed in controls. There was a direct relationship between DAS and GRalpha expression. CONCLUSIONS: Mechanisms involved in GC resistance observed in patients with RA are possibly not at the level of GRalpha gene expression, since it was similar among groups and GRalpha increased with disease activity.
20444757 Profound invariant natural killer T-cell deficiency in inflammatory arthritis. 2010 Oct OBJECTIVES: Data from rodent models indicate that invariant natural killer T (iNKT) cells are key regulators of many immune responses including autoimmune arthritis, but their role in human diseases is unclear. The aims of this study are to determine whether iNKT cell frequency and function are altered in patients with rheumatoid arthritis (RA), and the clinical significance of such iNKT cell abnormalities. METHODS: Peripheral blood iNKT cell frequency and proliferative response to an iNKT cell-specific agonist, α-galactosylceramide were measured in 46 RA patients (including 23 untreated, newly diagnosed patients), 22 healthy controls and 27 patients presenting with recent-onset joint pain. The relationship between iNKT cell frequency and clinical characteristics and the effects of immunosuppressive treatment was examined. RESULTS: Compared with healthy controls, RA patients had a decreased frequency of peripheral blood iNKT cells (median 0.001% vs 0.021%, p<0.001) and the proliferative response of this subset to α-galactosylceramide was also diminished in the patient group (median fold-expansion 31 vs 121, p=0.037). These abnormalities preceded the initiation of disease-modifying or immunosuppressive therapy, whose effect was to increase the circulating iNKT cell frequency (p=0.037). Furthermore, iNKT cell frequency correlated inversely with the systemic inflammatory marker, C-reactive protein (p=0.008). Finally, in patients presenting with recent-onset joint symptoms, normal peripheral blood iNKT cell frequency predicted a non-inflammatory cause of joint pain. CONCLUSION: iNKT cell deficiency is present in patients with RA and other inflammatory arthropathy. Normal iNKT cell frequency predicts non-inflammatory causes of joint pain.
21089442 [Distribution of allelic variants of promotor sites of cytokine genes and endothelial grow 2010 The article reports results of the first study of cytokine gene polymorphic sites and analysis of distribution of their complexes among healthy subjects and patients with rheumatoid arthritis (RA) representative of the Russian Europeoid population; their possible prognostic significance is evaluated. Comprehensive analysis of the frequency of allelic variants of cytokine genes IL1B C-31T, IL6 G-174C, TNFA A-238G, TNFA A-308G, TNFA A-863C, IL4 C-590T, IL10 A-592C and VEGF C-2578A was performed for 513 residents of the Novosibirsk region showing no obvious signs of any diseases and 125 RA patients. The results suggest association of RA with certain alleles of pro- and anti-inflammatory cytokine genes. Complex indices reflecting combinations of genotypes of two, three, four, five, six and seven loci of the explored cytokine genes found in individual patient demonstrate their high specificity for RA. It is supposed that these findings can be used in further clinical studies for the development of algorithm designed to detect risk groups among clinically healthy subjects.
20189875 Current aspects of anti-CD20 therapy in rheumatoid arthritis. 2010 Jun Although B cells represent major contributors to rheumatoid arthritis (RA) pathogenesis, their precise roles in the induction and maintenance of abnormal immune activation in this entity remains poorly understood. As proof of principle, rituximab, a chimeric B cell depleting anti-CD20-antibody, has demonstrated that depletion of B cells can substantially improve signs and symptoms as well as physical function and inhibit radiologic progression that led to the approval of this agent to treat patients with moderate to severe RA lacking response to TNF-alpha blocking agents in 2006. Placebo-controlled clinical trials as well as subsequent studies and experiences further contributed to our understanding of the mechanism of action of rituximab, but a number of open questions remain. This review summarizes some lessons learned from B cell depletion in RA including particular safety aspects. Of importance using this therapy is that it apparently provides the highest likelihood of response in seropositive RA patients. This observation differentiates it from other currently available therapies and closes the conceptual loop that the underlying immunopathogenesis involves B cells requiring 'targeted' therapy.
20022305 Rituximab treatment overcomes reduction of regulatory iNKT cells in patients with rheumato 2010 Mar Invariant natural killer T (iNKT) cells are a subset of T cells that recognize glycolipid antigens presented by the CD1d molecule. Accumulating evidences showed that iNKT cells are implicated in the regulatory mechanisms that control autoimmunity. We evaluated the number of circulating iNKT cells in patients with rheumatoid arthritis (RA) by flow cytometry and performed a longitudinal analysis of iNKT cell frequency in RA patients who were given an anti-CD20 therapy. Significantly lower iNKT cell numbers were measured in the blood from RA patients compared to healthy individuals (p<0.0001) and low iNKT cell frequencies were rather associated with an active disease. In RA patients who received rituximab treatment, iNKT cell number was increased in relation to the clinical outcome. We demonstrated that the number of iNKT cells is altered in RA patients and that following rituximab therapy, clinical remission of RA is associated with an increase of iNKT cell frequency.
18713784 Effects of infliximab therapy on biological markers of synovium activity and cartilage bre 2009 Jul BACKGROUND: Defining the remission criteria of rheumatoid arthritis (RA) remains a critical issue. Markers of synovium activity, urinary glucosyl-galactosyl-pyridinoline (Glc-Gal-PYD) and of cartilage destruction, urinary C-terminal crosslinking telopeptide of type II collagen (CTX-II) have been shown to reflect disease activity and joint damage progression in RA. METHODS: The prospective study cohort comprised 66 RA patients treated with infliximab and methotrexate and 76 healthy controls. Measurements of urinary Glc-Gal-PYD and CTX-II were performed at baseline and at 1 year of infliximab therapy. RESULTS: At baseline, urinary Glc-Gal-PYD and CTX-II levels were increased in patients with RA and correlated with modified Sharp scores and progression of joint damage. Patients with more progressive joint destruction had higher Glc-Gly-PYD and CTX-II baseline levels. CONCLUSION: These markers reflected bone erosion evolution and might be useful for treatment monitoring and evaluation of RA. Markers remained high even in clinical responders after infliximab, suggesting persistence of synovitis.
20648402 Swiss consensus statement: Recommendations for optimising re-treatment with MabThera (ritu 2010 Rituximab is an effective treatment of rheumatoid arthritis (RA), which has been approved for the treatment of moderate to severe disease in patients with an inadequate response to anti-TNF therapies. Rituximab differs from other available biological agents for RA by way of its unique mode of action and unrivalled long dosing interval. The efficacy of rituximab subsides progressively over time and re-therapy is generally required to maintain long term disease control. The timing of re-treatment is currently not well established and varies widely in clinical practice. The present document is a concise recommendation regarding re-treatment with rituximab, based on validated outcomes such as the DAS28 and the EULAR response criteria. The recommendation was established through consensus between practitioners familiar with rituximab therapy in RA. Optimisation of the rituximab re-treatment schedule may improve patient outcomes and balance risks and benefits for the individual patient.
19627016 [Predictive values of anti-cyclic citrullinated peptide antibody, antikeratin antibody and 2009 May OBJECTIVE: To explore the diagnostic significance of anti-cyclic citrullinated peptide (CCP) antibody (anti-CCP), antikeratin antibody (AKA) and rheumatoid factor (RF) for predicting articular erosions in patients with rheumatoid arthritis (RA). METHODS: One hundered and fifty eight RA patients were devided into 2 groups [limited radiographic damage group (Group 1) and severe radiographic damage group (Group 2)] based on the Larsen's score system. Enzyme linked immunosorbent assay, indirect immunofluorescence and rate naphelometry were used to measure anti-CCP, AKA and RF, respectively. RESULTS: The sensitivity and specificity of Anti-CCP, AKA and RF for detecting RA were 49% and 94%, 50% and 93%, and 79% and 67%, respectively. The specificity increased when any two markers were combined. The patients with severe radiographic damage had higher positive rates of these three antibodies than the patients with limited radiographic damage. Anti-CCP had the highest OR (6.71) for predicting articular erosions in RA patients. The logistic regression analysis showed a strong correlation between anti-CCP, AKA, CRP or cutaneous nodules and the severity of articular erosions. Anti-CCP had the strongest correlation with the severe radiographic damages. CONCLUSION: Anti-CCP has advantages over the other two antibodies in diagnosing RA. However, the diagnostic accuracy can be improved when anti-CCP is combined with AKA or RF. Anti-CCP and AKA have strong correlations with severe articular erosions, which will be helpful for predicting the outcomes of RA.
20549518 Identification of HAVCR1 gene haplotypes associated with mRNA expression levels and suscep 2010 Aug Human HAVCR1 gene maps on 5q33.2, a region linked with susceptibility to allergic and autoimmune diseases. The aims of the present study were to define the haplotypes of HAVCR1 gene taking into account both HapMap Project SNP haplotypes and exon 4 variants, to investigate a possible relationship between these haplotypes and mRNA expression levels, and to assess whether HAVCR1 gene is involved in susceptibility to rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Genotyping of three ins/del variants in the exon 4 was performed by fragment length analysis. Five tag SNPs genotypes and mRNA levels were determined using TaqMan assays. We defined four major haplotypes in our population: the two major haplotypes (named haplotypes A and B) bear both the 5383_5397del variant and the two most common SNP sets found in the CEU population. Quantification analysis revealed that genotype B/B had the highest median of mRNA expression levels (vs. BX + XX, p < 0.0001). Additionally, frequency of the genotype BB was significantly higher in RA patients than in controls (12.3 vs. 5.9% in controls, p = 0.0046, p (c) = 0.014, OR = 2.23, 95% CI 1.23-4.10). Our results support a relationship between HAVCR1 haplotypes and mRNA expression levels, and suggest an association of this gene with autoimmune diseases.
20547657 Epstein-Barr virus in bone marrow of rheumatoid arthritis patients predicts response to ri 2010 Oct OBJECTIVES: Viruses may contribute to RA. This prompted us to monitor viral load and response to anti-CD20 therapy in RA patients. METHODS: Blood and bone marrow from 35 RA patients were analysed for CMV, EBV, HSV-1, HSV-2, parvovirus B19 and polyomavirus using real-time PCR before and 3 months after rituximab (RTX) treatment and related to the levels of autoantibodies and B-cell depletion. Clinical response to RTX was defined as decrease in the 28-joint disease activity score (DAS-28) >1.3 at 6 months. RESULTS: Before RTX treatment, EBV was identified in 15 out of 35 patients (EBV-positive group), of which 4 expressed parvovirus. Parvovirus was further detected in eight patients (parvo-positive group). Twelve patients were negative for the analysed viruses. Following RTX, EBV was cleared, whereas parvovirus was unaffected. Eighteen patients were responders, of which 12 were EBV positive. The decrease in the DAS-28 was significantly higher in EBV-positive group compared with parvo-positive group (P = 0.002) and virus-negative patients (P = 0.04). Most of EBV-negative patients that responded to RTX (75%) required retreatment within the following 11 months compared with only 8% of responding EBV-positive patients. A decrease of RF, Ig-producing cells and CD19(+) B cells was observed following RTX but did not distinguish between viral infections. However, EBV-infected patients had significantly higher levels of Fas-expressing B cells at baseline as compared with EBV-negative groups. CONCLUSIONS: EBV and parvovirus genomes are frequently found in bone marrow of RA patients. The presence of EBV genome was associated with a better clinical response to RTX. Thus, presence of EBV genome may predict clinical response to RTX.
19473561 Anti-TNF-alpha therapy does not modulate leptin in patients with severe rheumatoid arthrit 2009 Mar OBJECTIVE: The adipocytokine leptin regulates weight centrally and participates in the regulation of the immune and inflammatory responses. Chronic systemic inflammation is of major importance in the development of atherosclerosis in rheumatoid arthritis (RA). In the present study we investigated whether inflammation, obesity or both of these characteristics are potential determinants of circulating leptin concentrations in a group of RA patients on periodical treatment with the TNF-alpha-blocker-infliximab due to severe disease. We also assessed whether the infusion of infliximab may alter circulating leptin concentrations in patients with severe RA. METHODS: We investigated 33 patients with RA on periodical treatment with infliximab. Serum leptin levels were determined immediately prior to and after infliximab infusion. RESULTS: There was a positive correlation between body mass index of RA patients and baseline serum level of leptin (rho=0.665, p<0.001). Apart from a significant correlation with VCAM-1 (rho=0.349, p=0.04), no significant correlations between baseline leptin levels and the age at the time of the study or at the onset of the disease, disease duration, ESR and CRP levels, DAS28, lipids, insulin sensitivity, adhesion molecules, resistin, adiponectin, ghrelin or the cumulative prednisone dose at the time of the study were found. Leptin levels did not change upon infliximab infusion (p=0.48). CONCLUSION: In RA patients on TNF-alpha blocker treatment, circulating leptin levels are unrelated to disease activity but constitute a manifestation of adiposity. The beneficial effect of anti-TNF-alpha therapy on cardiovascular mortality in RA does not seem to be mediated by reduction in serum levels of leptin.
19646340 Interleukin-12 gene polymorphisim in patients with giant cell arteritis, polymyalgia rheum 2009 Jan OBJECTIVE: The cytokine profile suggests that giant cell arteritis (GCA) is a Th1-driven disease, in which local IFN-gamma plays a critical role in the development of a systemic arteritis. IL-12 is a potent inducer of IFN-gamma and is critically involved in biasing an immune response towards a Th1 pathway. The purpose of this study was to investigate whether there was an association between an IL-12 gene polymorphism (-1188 A/C 3UTR) and disease susceptibility for GCA and two other age-related inflammatory conditions, such as polymyalgia rheumatica (PMR) and elderly-onset rheumatoid arthritis (EORA). Furthermore, we attempted to correlate such polymorphism with in vitro IL-12 production. MATERIALS AND METHODS: We analyzed genotypes at -1188 in the 3UTR of the IL-12 promoter by PCR-RFLP in 68 GCA, 138 PMR, and 72 EORA patients as well as in 465 healthy controls (HC). IL-12p70 levels in culture supernatants after stimulation with PMA+Ionomycin was assessed by ELISA. RESULTS: All groups were in Hardy-Weinberg equilibrium. Allelic and gen-omic distribution was not significantly different among the study groups. None of the genetic variants was associated with disease severity. Although the differences were not statistically significant, HC genotypes were associated with distinct IL-12 p70 production. CONCLUSIONS: The IL-12 (-1188 A/C 3UTR) gene polymorphism is not associated with disease susceptibility or severity in three age-related chronic inflammatory syndromes. The production of IL-12 p70 is dependent on the genetic background in HC, although in patients such association may be biased by other unknown factors.