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ID PMID Title PublicationDate abstract
21366908 Risk factors for ANA positivity in healthy persons. 2011 Mar 2 INTRODUCTION: The finding of antinuclear antibody (ANA) positivity in a healthy individual is usually of unknown significance and in most cases is benign. However, a subset of such individuals is at risk for development of autoimmune disease. We examined demographic and immunological features that are associated with ANA positivity in clinically healthy persons to develop insights into when this marker carries risk of progression to lupus. METHODS: Biological samples from healthy individuals and patients with systemic lupus erythematosus (SLE) were obtained from the Dallas Regional Autoimmune Disease Registry (DRADR). Measurements carried out on serum samples included ANA, extractable nuclear antibodies (ENA) and autoantibody profiling using an array with more than 100 specificities. Whole blood RNA samples from a subset of individuals were used to analyze gene expression on the Illumina platform. Data were analyzed for associations of high ANA levels with demographic features, the presence of other autoantibodies and with gene expression profiles. RESULTS: Overall, ANA levels are significantly higher in females than in males and this association holds in patients with the autoimmune diseases lupus and rheumatoid arthritis (RA) as well as in healthy controls (HC). Age was not significantly associated with ANA levels and the elevated ANA values could not be explained by higher IgG levels. Another autoantibody, anti- cyclic citrullinated peptide (CCP), did not show gender dimorphism in rheumatoid arthritis (RA) or healthy individuals. The autoantigen array showed significant elevations of other autoantibodies in high ANA HCs. Some of these autoantibodies were directed to antigens in skin and others were related to autoimmune conditions of kidney, thyroid or joints. Gene expression analyses showed a greater prevalence of significantly upregulated genes in HCs with negative ANA values than in those with significant ANA positivity. Genes upregulated in high ANA HCs included a celiac disease autoantigen and some components of the Type I interferon (IFN) gene signature. CONCLUSIONS: Risks for ANA positivity include female gender and organ-specific autoimmunity. Upregulation of skin-specific autoantibodies may indicate that early events in the break of tolerance take place in cutaneous structures. Some of these changes may be mediated by Type I IFN. Blood profiling for expressed autoantibodies and genes has the potential to identify individuals at risk for development of autoimmune diseases including lupus.
21960560 A mixed treatment comparison of the efficacy of anti-TNF agents in rheumatoid arthritis fo 2012 Feb BACKGROUND: A number of tumour necrosis factor α (TNFα) antagonists (anti-TNFα) are available to treat rheumatoid arthritis. All of these have demonstrated considerable efficacy in placebo controlled trials, but few head-to-head comparisons exist to date. This work's objective is to estimate the relative efficacy among licensed anti-TNFs in patients who have had an inadequate response to methotrexate (MTX). Different outcome measures are used to highlight the advantages of continuous measures in such analyses. METHODS: A systematic review identified randomised controlled trials comparing the efficacy of licensed anti-TNFα agents with placebo at 24 weeks in patients who have had an inadequate response to MTX. Relative efficacy was estimated using Bayesian mixed treatment comparison (MTC) models. Three different outcome measures were used: RR of achieving an American College of Rheumatology (ACR) 20 and ACR50 response and the percentage improvement in Health Assessment Questionnaire (HAQ) score. RESULTS: 16 published trials were included in the analysis. All anti-TNFs show considerably improved efficacy over placebo. The MTC results also provide evidence of some differences in efficacy of the TNFα antagonists. Etanercept appears superior to infliximab and golimumab, and certolizumab to infliximab and adalimumab. ACR results indicate improved efficacy of certolizumab over golimumab. On HAQ analysis, adalimumab, certolizumab, etanercept and golimumab appear superior to infliximab, and etanercept shows improved efficacy compared with adalimumab. CONCLUSIONS: There are differences in efficacy among the TNFα antagonists. In a MTC, a continuous outcome measure has more strength to detect such differences than a binomial outcome measure because of its enhanced sensitivity to change.
22430489 A novel pathogenic role of the ER chaperone GRP78/BiP in rheumatoid arthritis. 2012 Apr 9 An accumulation of misfolded proteins can trigger a cellular survival response in the endoplasmic reticulum (ER). In this study, we found that ER stress-associated gene signatures were highly expressed in rheumatoid arthritis (RA) synoviums and synovial cells. Proinflammatory cytokines, such as TNF and IL-1β, increased the expression of GRP78/BiP, a representative ER chaperone, in RA synoviocytes. RA synoviocytes expressed higher levels of GRP78 than osteoarthritis (OA) synoviocytes when stimulated by thapsigargin or proinflammatory cytokines. Down-regulation of Grp78 transcripts increased the apoptosis of RA synoviocytes while abolishing TNF- or TGF-β-induced synoviocyte proliferation and cyclin D1 up-regulation. Conversely, overexpression of the Grp78 gene prevented synoviocyte apoptosis. Moreover, Grp78 small interfering RNA inhibited VEGF(165)-induced angiogenesis in vitro and also significantly impeded synoviocyte proliferation and angiogenesis in Matrigel implants engrafted into immunodeficient mice. Additionally, repeated intraarticular injections of BiP-inducible factor X, a selective GRP78 inducer, increased synoviocyte proliferation and angiogenesis in the joints of mice with experimental OA. In contrast, mice with Grp78 haploinsufficiency exhibited the suppression of experimentally induced arthritis and developed a limited degree of synovial proliferation and angiogenesis. In summary, this study shows that the ER chaperone GRP78 is crucial for synoviocyte proliferation and angiogenesis, the pathological hallmark of RA.
22040886 Dihydrotestosterone inhibits interleukin-1α or tumor necrosis factor α-induced proinflam 2011 Rheumatoid arthritis (RA) is a disease with significant gender differences in its prevalence and clinical features. Interleukin (IL)-1 and tumor necrosis factor (TNF) α produced by synoviocytes are principle inflammatory and destructive mediators of RA. We found that a potent androgen, 5α-dihydrotestosterone (DHT) inhibits IL-1α-induced production and mRNA expression of IL-8, IL-6 and IL-1β from RA patient-derived fibroblast-like synovial cell line MH7A. Promoter analysis of the IL-8 gene revealed that nuclear factor (NF)-κB activation is critical for its transcriptional activation by IL-1α, and DHT inhibited the IL-1α-induced NF-κB activation in a manner dependent on the androgen receptor (AR). DHT also inhibited the effects of TNFα on the cells overexpressed with AR, indicating that sufficient expression level of functional AR was necessary for the inhibitory effect of DHT on TNFα. These results suggest that androgen contributes to the prevention against RA and its gender difference by inhibiting IL-1α or TNFα-induced proinflammatory cytokine production from synovial fibroblast-like cells by inhibiting NF-κB activation in a manner depending on AR.
21931942 Early aggressive intervention with tocilizumab for rheumatoid arthritis increases remissio 2012 Jun The goal of treating rheumatoid arthritis (RA) should be remission, for which a new definition was proposed in 2011. To determine which patients can achieve the new Boolean-based definition of remission in clinical practice, we analyzed factors associated with remission in 123 patients who received tocilizumab for 52 weeks. We found that patients with short disease duration (<4.8 years) had a significantly higher rate of remission (31.7%) than those with longer disease duration, and patient global assessment was the most important factor for achieving remission. Multivariate analysis revealed the following predictors of remission: short disease duration [<4.8 years; odds ratio (OR) 2.5, 95% confidence interval (CI) 1.4-4.7] and lower disease activity [28-joint disease activity score-erythrocyte sedimentation rate (DAS28-ESR) <5.23; OR 2.5, 95% CI 1.2-5.1). In this study, we showed that remission, as newly defined using a Boolean approach, is a realistic goal for patients treated with tocilizumab with short disease duration in real-world clinical practice.
21732349 Role of insulin-like growth factors (IGFs), their receptors and genetic regulation in the 2012 May Growth of the mandibular condylar cartilage (MCC) is reviewed as a function of genetic and epigenetic factors. The growth centers around the differential spatial concentration of the chondrocytes, influence of growth factors like TGF-β and heterogeneity in the number of IGF receptors, control the action of IGF. Besides these factors, growth of the mandibular condyle is influenced by differential response of chondrocytes as a function of their source/ageing, which in turn is regulated by TGF-β, BMPs and IGFs. While IGF-1 promotes proteoglycan synthesis and survival of the chondrocytes to maintain cartilage homeostasis, TGF-β synergistically catalysed the effect of IGF-1, while BMPs catalysed proteolysis as and when physiologically needed. To understand these processes, role of IGF-1 and its six receptors is at the center to a number of physiological processes being regulated by its mode of application for the growth and differentiation. Probing deeper, biological functions of IGFs seemed to depend on their level of free status rather than bound status to respective IGF-binding proteins (IGF-BPs), considered prerequisite to modulate their biological functions. Genetic regulation of their secretion has thrown light on their insulin-like structural homology, level and response in osteo-arthritis (OA), rheumatic arthritis (RA) and diabetes type-II. Biochemistry and spatial distribution of IGF receptors in different domains exerts control on IGF-1 activities. In ultimate analysis, IGF-axis conserved during the evolution to regulate cell growth and proliferation affect nearly every organ in the body as judged from the techniques determining skeletal maturity and decision making dependent on it for orthodontic, orthognathic/orthopedic and dental implant applications.
22519396 Discovery of selective small molecular TACE inhibitors for the treatment of rheumatoid art 2012 Rheumatoid arthritis (RA) is a chronic, inflammatory disease that afflicts 1-2% of the world population, characterized by an immune mediated inflammatory synovitis that leads to joint destruction, functional impairment, and reduced quality of life. The treatment goals of RA should be longterm substantial relief of pain, arrested joint inflammation and damage, and improved function. Current treatment can be divided into four classes, namely general analgesics and non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, disease modifying anti-rheumatic drugs (DMARDs) and biological agents (tumor-necrosis factor modifiers). However, gastrointestinal (GI) side effects of NSAIDs cannot be neglected, direct joint injections of glucocorticoids cannot be injected more than once every 3 months, synthetic DMARDs is far from optimal and only minority of patients achieved longterm remission, the biologics are very expensive to manufacture, need to be injected, and can cause allergic reactions. An alternative and good approach to the treatment of this disease is to lower the levels of tumour necrosis factor-α (TNF-α) in RA, which can be achieved by selectively inhibiting the tumour necrosis factor-α converting enzyme (TACE) that generate these cytokines using cheaper small molecules. This review focuses on the current status of selective small molecule inhibitors of TACE, with respect to lead compound search, inhibitors design approach, structure-activity relationship (SAR) and pharmacological studies in animals and humans. Through these methods, new hope is emerging for the treatment of RA through selective inhibition of TACE.
21523342 Association of Rsa polymorphism of the estrogen receptor-β gene with rheumatoid arthritis 2012 Jul To investigate the possible influence of the single nucleotide polymorphism (SNP) of the estrogen receptor-β gene, rs1256049 (Rsa) in exon 5, on the frequency of rheumatoid arthritis (RA), 263 RA patients and 174 control subjects with osteoarthritis (OA) were recruited. Rsa polymorphism was detected using a PCR-RFLP, Polymerase Chain Reaction-Restriction Fragment Length Polymorphism method. The occurrence of both mutant allele (G) and genotype (GG) were significantly higher in RA than in OA patients (allele P = 0.008, OR: 1.501, 95%CI: 1.12-2.02). In RA patients, GG genotype frequency was higher in severe RA patients than mild RA patients. Moreover, there was significant difference between severe RA patients and OA patients (P = 0.009), also the allele distribution was significant different between severe RA, mild RA, and OA patients (P = 0.025, 95%CI = 0.61-0.93). With respect to gender, GG genotype was statistically more frequent in female RA patients than that of OA, while such an association was not observed in men. Above all, the presence of the GG genotype could be a risk factor for RA and such trend might be different in gender, although additional larger scale study is needed.
22785189 Nocardia neocaledoniensis [corrected] as a cause of skin and soft tissue infection. 2012 Sep Nocardia neocaledoniensis was introduced as a new environmental species of Nocardia in 2004. We present the first case of human skin and soft tissue infection caused by this species in a patient with rheumatoid arthritis receiving prednisone and methotrexate therapy.
22942082 Genomic dissection and prioritizing of candidate genes of QTL for regulating spontaneous a 2012 Aug Rheumatoid arthritis is a heterogeneous disease with clinical and biological polymorphisms. IL-1RN is a protein that binds to interleukin-1 (IL-1) receptors and inhibits the binding of IL-1-alpha and IL-1-beta. IL-1RN levels are elevated in the blood of patients with a variety of infectious, immune, and traumatic conditions. Balb/c mice deficient in IL-1ra (mouse gene of IL-1RN) develop spontaneous autoimmune arthritis while DBA/1 mice deficient in IL-1ra do not. Previously, we identified a major QTL that regulates the susceptibility to arthritis in Balb/c mice with IL-1ra deficiency. In this study, we found that the QTL may contain two peaks that are regulated by two sets of candidate genes. By haplotype analysis, the total genomic regions of candidate genes were reduced from about 19 Mbp to approximately 9 Mbp. The total number of candidate genes was reduced from 208 to 21.
21354359 Prospective study of a new total wrist arthroplasty: short term results. 2011 Feb We present early results (average 32 months follow-up, minimum 12 months) of a prospective study of the ReMotionâ„¢ total wrist arthroplasty in a series of 20 wrists (19 patients) with end-stage arthritic wrists (of whom 13 were rheumatoid). Overall there were no intra-operative complications, dislocations or reoperations. We observed one carpal and one radial loosening--both in rheumatoid patients. Neither was symptomatic enough to warrant reoperation. In the rheumatoid group of 13 wrists there was an average of 41% clinical score improvement. According to the Meuli score there were seven excellent, five good and one poor result. In the non-rheumatoid group of seven wrists there was an average of 27% clinical score improvement. According to the Meuli score there were two excellent, two good, two fair and one poor result. In the short term follow-up of this series, the ReMotionâ„¢ total wrist arthroplasty provided better results and less devastating complications than the old generation total wrist arthroplasties. Longer follow-up is needed to validate these early results.
21390051 Fine mapping the TAGAP risk locus in rheumatoid arthritis. 2011 Jun A common allele at the TAGAP gene locus demonstrates a suggestive, but not conclusive association with risk of rheumatoid arthritis (RA). To fine map the locus, we conducted comprehensive imputation of CEU HapMap single-nucleotide polymorphisms (SNPs) in a genome-wide association study (GWAS) of 5,500 RA cases and 22,621 controls (all of European ancestry). After controlling for population stratification with principal components analysis, the strongest signal of association was to an imputed SNP, rs212389 (P=3.9 × 10(-8), odds ratio=0.87). This SNP remained highly significant upon conditioning on the previous RA risk variant (rs394581, P=2.2 × 10(-5)) or on a SNP previously associated with celiac disease and type I diabetes (rs1738074, P=1.7 × 10(-4)). Our study has refined the TAGAP signal of association to a single haplotype in RA, and in doing so provides conclusive statistical evidence that the TAGAP locus is associated with RA risk. Our study also underscores the utility of comprehensive imputation in large GWAS data sets to fine map disease risk alleles.
22281925 Rheumatoid nodules: evaluation of the therapeutic response to intralesional fluorouracil a 2011 Nov Rheumatoid nodules are the most common extra-articular manifestation of rheumatoid arthritis and are present in around 20-25% of patients. Their etiology is unknown and although the nodules may undergo spontaneous remission during the treatment of rheumatoid arthritis, they usually constitute a therapeutic challenge. The present paper describes a case in which the response of rheumatoid nodules was evaluated by ultrasound following infiltration of triamcinolone acetonide and 5-fluorouracil.
22389040 2012 Provisional classification criteria for polymyalgia rheumatica: a European League Aga 2012 Apr The objective of this study was to develop European League Against Rheumatism/American College of Rheumatology classification criteria for polymyalgia rheumatica (PMR). Candidate criteria were evaluated in a 6-month prospective cohort study of 125 patients with new-onset PMR and 169 non-PMR comparison subjects with conditions mimicking PMR. A scoring algorithm was developed based on morning stiffness >45 minutes (2 points), hip pain/limited range of motion (1 point), absence of rheumatoid factor and/or anti-citrullinated protein antibody (2 points), and absence of peripheral joint pain (1 point). A score ≥4 had 68% sensitivity and 78% specificity for discriminating all comparison subjects from PMR. The specificity was higher (88%) for discriminating shoulder conditions from PMR and lower (65%) for discriminating RA from PMR. Adding ultrasound, a score ≥5 had increased sensitivity to 66% and specificity to 81%. According to these provisional classification criteria, patients ≥50 years old presenting with bilateral shoulder pain, not better explained by an alternative pathology, can be classified as having PMR in the presence of morning stiffness >45 minutes, elevated C-reactive protein and/or erythrocyte sedimentation rate, and new hip pain. These criteria are not meant for diagnostic purposes.
22034096 Interleukin-22 promotes osteoclastogenesis in rheumatoid arthritis through induction of RA 2012 Apr OBJECTIVE: To examine the regulatory role of interleukin-22 (IL-22) in the expression of RANKL and induction of osteoclastogenesis in rheumatoid arthritis (RA). METHODS: Concentrations of IL-22 and RANKL in the serum and synovial fluid of RA patients were measured using enzyme-linked immunosorbent assay. RA synovial fibroblasts were treated with recombinant human IL-22 (rhIL-22), and the expression of RANKL messenger RNA (mRNA) and protein was measured using real-time polymerase chain reaction, Western blotting, and intracellular immunostaining. Human monocytes were cocultured with IL-22-prestimulated RA synovial fibroblasts and macrophage colony-stimulating factor, and osteoclastogenesis was assessed by counting the multinucleated cells (those staining positive for tartrate-resistant acid phosphatase). RESULTS: The IL-22 concentration in the synovial fluid was higher in RA patients than in patients with osteoarthritis (OA). The serum IL-22 concentration was also higher in RA patients than in OA patients and healthy volunteers, and this correlated with serum titers of rheumatoid factor and anti-cyclic citrullinated peptide antibodies. In RA synovial fibroblasts treated with rhIL-22, the expression of RANKL mRNA and protein was increased in a dose-dependent manner. IL-22-induced RANKL expression was down-regulated significantly by the inhibition of p38 MAPK/NF-κB or JAK-2/STAT-3 signaling. In human monocytes cocultured with IL-22-prestimulated RA synovial fibroblasts in the absence of exogenous RANKL, the monocytes differentiated into osteoclasts, but this osteoclastogenesis decreased after p38 MAPK/NF-κB or JAK-2/STAT-3 signaling was inhibited. CONCLUSION: These results show that IL-22 up-regulates RANKL expression in RA synovial fibroblasts and induces osteoclastogenesis. These effects are mediated by the p38 MAPK/NF-κB and JAK-2/STAT-3 signaling pathways.
22910140 Adiponectin: a biomarker for rheumatoid arthritis? 2013 Feb Recent achievements in the biology and the function of adipose tissue have regarded white adipose tissue (WAT) as an important endocrine and secretory organ. Releasing a series of multiple-function mediators, WAT is involved in a wide spectrum of diseases, including not only cardiovascular and metabolic complications, such as atherosclerosis and type 2 diabetes, but also inflammatory- and immune-related disorders, such as rheumatoid arthritis (RA) and osteoarthritis (OA). A large number of these mediators, called adipokines, such as tumor necrosis factor alpha (TNF-α), leptin, adiponectin, resistin, chemerin, interleukin-6 (IL-6), visfatin, and so on have been identified and studied widely. Important advances related to these proteins shed new insights into the pathophysiological mechanisms of many complicated diseases, although details of which remain unclear. Adiponectin, one of the most widely investigated adipokine, has been shown to possess both anti- and pro-inflammatory effects. RA is a chronic systemic inflammatory-related autoimmune disease. Accumulated evidence has demonstrated that cytokines and adipokines play an important role in the pathogenesis of RA. In this review, we have summarized the most recent advances in adiponectin research in the context of RA, focusing primarily on its effect on RA-related cells, its regulation on pro-inflammatory cytokines, as well as its validation as a biomarker for RA.
23200852 MeCP2 modulates the canonical Wnt pathway activation by targeting SFRP4 in rheumatoid arth 2013 Mar Rheumatoid arthritis (RA) is an autoimmune disease characterized by the rheumatoid factor and anti-citrullinated peptide antibody (ACPA) against common autoantigens that are widely expressed within and outside the joints. Many factors participate in the pathogenesis of RA, such as cytokine imbalance, Wnt pathway activation, matrix production, and osteoprotegerin on osteoclasts. Fibroblast-like synoviocytes (FLS) activation has an important role in RA pathogenesis. The methyl-CpG-binding protein (MeCP2) which promoted repressed chromatin structure was selectively detected in synovium of diseased articular in rats. Overexpression of this protein results in an up-regulation of global methylation levels and transcriptional suppression of specific genes. There were increased MeCP2 and decreased secreted frizzled-related protein 4 (SFRP4) in synovium as well as the FLS isolated from the synovium of RA rats. Knockdown of MeCP2 using siRNA technique enhanced SFRP4 expression in both mRNA and protein levels in FLS. These results indicated that epigenetic modification was involved in differential expression of SFRP4. To further explore the underlying molecular mechanisms, we hypothesized that the SFRP4 down-regulation in synovium was caused by DNA methylation. Treatment of FLS with DNA methylation inhibitor 5-Aza-2'-deoxycytidine (5-azadC) blocked the cell proliferation and increased the SFRP4 expression. Increased SFRP4 down-regulated the key gene β-catenin, the downstream effectors gene ccnd1 and fibronectin expression in canonical Wnt pathway at the same time. MeCP2 and DNA methylation may provide molecular mechanisms for canonical Wnt pathway activation in RA. Combination of 5-azadC and MeCP2 may be a promising treatment strategy for individuals with RA in which SFRP4 is inactivated.
23202712 [Lung carcinoma in a patient with rheumatoid arthritis treated with tumor necrosis factor 2012 Dec A 65-year-old male was referred to our department because of an abnormal shadow on chest X-ray. He had been suffering from rheumatoid arthritis for 10 years. He had been treated with tumor necrosis factor antagonist(etanercept)for the past 3 years and 6 months. Computed tomography of the chest revealed an irregular shaped pulmonary nodule with the longest diameter of 4.3 cm in the left upper lobe. The diagnosis of lung carcinoma was made. He underwent video-assisted left upper lobectomy with lymph node dissection. Histological examination revealed poorly differentiated squamous cell carcinoma. The tumor was classified as stage â…¢A with T4(pm2)N1M0. No adjuvant chemotherapy was performed because he had recurrent arthralgia after operation and new anti-rheumatic-drug was required. He is free from disease with a follow-up period of 11 months.
21226240 Surgical synovectomy decreases density of sensory nerve fibers in synovial tissue of non-i 2011 Feb Surgical synovectomy is a technique to treat synovitis and pain in patients with rheumatoid arthritis (RA) resistant to DMARDs or therapy with biologics. Indication to synovectomy is subject to tight cooperation of orthopaedic surgeons and rheumatologists. It was thought that synovectomy leads to a reduction of sensory nerve fibers, called sensory denervation. Since sensory denervation after synovectomy has never been histologically tested, we aimed to investigate sensory and sympathetic innervation in synovial tissue before and after synovectomy. Eight non-inflamed control subjects and eight patients with RA were included in this study with a two-stage synovectomy approach (interval 40–50 days). Nerve fibers and cells in synovial tissue were detected and counted using immunofluorescence. Density of sympathetic nerve fibers did not change after synovectomy, whereas density of sensory nerve fibers decreased in all control subjects and seven of eight patients with RA. In parallel, the density of synovial cells increased after synovectomy in all control subjects and six of eight RA patients, which is indicative of a wound healing response. In one female RA patient, density of sensory nerve fibers increased and a very marked rise of cellular density was observed, too. This indicates that probably not all patients profit from surgical synovectomy. The majority of patients (94%) demonstrated sensory denervation after surgical synovectomy accompanied by a wound healing cell response. This study can help to explain the positive effects of surgical synovectomy which usually leads to pain reduction and improved mobility.
21816071 Incorporation of n-3 PUFA and γ-linolenic acid in blood lipids and red blood cell lipids 2011 Aug 4 BACKGROUND AND AIM: Marine n-3 fatty acids and γ-linolenic acid both have anti-inflammatory effects and may be useful to help treat inflammatory diseases. The effects of these alone or combined were examined in patients with arthritis in a randomized controlled trial. DESIGN: Patients with rheumatoid arthritis or psoriatic arthritis were randomized into four groups in a double-blind, placebo-controlled parallel designed study. Patients received the respective capsules (1: 3.0 g n-3 LC-PUFA/d; 2: 3.2 g γ-linolenic acid/d; 3: 1.6 g n-3 LC-PUFA + 1.8 g γ-linolenic acid/d; 4: 3.0 g olive oil) for a twelve week period. Clinical status was evaluated and blood samples were taken at the beginning and at the end of the period. Differences before and after intervention were tested with paired t-test or with Wilcoxon test for non-normal data distribution. RESULTS: 60 patients (54 rheumatoid arthritis, 6 psoriatic arthritis) were randomised, 47 finished per protocol. In group 1, the ratio of arachidonic acid (AA)/eicosapentaenoic acid (EPA) decreased from 6.5 ± 3.7 to 2.7 ± 2.1 in plasma lipids and from 25.1 ± 10.1 to 7.2 ± 4.7 in erythrocyte membranes (p ≤ 0.001). There was no significant influence on AA/EPA ratio due to interventions in group 2-4. In group 2, the intake of γ-linolenic acid resulted in a strong rise of γ-linolenic acid and dihomo-γ-linolenic acid concentrations in plasma lipids, cholesteryl esters, and erythrocyte membranes. The combination of n-3 LC-PUFA and γ-linolenic acid (group 3) led to an increase of γ-linolenic acid and dihomo-γ-linolenic acid concentrations in plasma lipids, cholesteryl esters, and erythrocyte mem-branes. This increase was only half of that in group 2. CONCLUSIONS: Incorporation of eicosanoid precursor FAs was influenced by an intake of n-3 LC-PUFA and γ-linolenic acid suggesting a possible benefit for therapy of chronic inflammatory diseases. TRIAL REGISTRATION: ClinicalTrials NCT01179971.