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ID PMID Title PublicationDate abstract
22985259 Role of peroxynitrite-modified H2A histone in the induction and progression of rheumatoid 2012 OBJECTIVE: Rheumatoid arthritis (RA) is an autoimmune disease of complex aetiology and pathogenesis. In recent years it has become evident that apoptotically modified histones exert a central role in the induction of autoimmunity, for example in systemic lupus erythematosus (SLE) and RA. Because nitric oxide (NO)-related species have been found in inflamed joints of arthritis patients, we investigated whether nitrotyrosine is present in sera of RA patients, and whether peroxynitrite-modified H2A histone is likely to be involved in the induction and progression of RA. METHODS: Commercially available H2A histone was modified in vitro by peroxynitrite. The RA patients were divided into three groups on the basis of CRP, nitrite, total protein and IgG level. Sera of RA patients with high-titre rheumatoid factor (RF) were analysed for autoantibodies against native DNA and native and peroxynitrite-modified H2A histone. Binding characteristics and specificity of the autoantibodies were analysed by direct binding, inhibition enzyme-linked immunosorbent assay (ELISA), and band shift assay. RESULTS: Sera from control subjects contained almost negligible amounts of 3-nitrotyrosine (3-NT); lower levels were found in group 1 RA patients in comparison to group 2 and group 3 patients, where the level of nitrotyrosine was progressively higher. Enzyme immunoassay data showed preferential binding of RA autoantibodies to peroxynitrite-modified H2A histone in comparison with native H2A histone or native DNA. The results suggest that peroxynitrite modification of self-antigen(s) can generate neoepitopes capable of inducing RA characteristic autoantibodies. CONCLUSION: The preferential binding of peroxynitrite-modified histones by autoantibodies derived from RA sera indicates a role for oxidatively modified and nitrated proteins in the initiation/progression of RA.
23275387 Low-dose prednisolone in early rheumatoid arthritis inhibits collagen type I degradation b 2013 Apr OBJECTIVE: To study the effects of low-dose prednisolone on the osteoclast-regulating proteins osteoprotegerin (OPG) and RANK ligand (RANKL) and on markers of bone resorption, 1CTP generated by MMPs and CTX-1 generated by cathepsin K, in patients with early RA in relation to inflammation and joint destruction. METHODS: In 225 patients, who at the start of the first DMARD had been randomized to 7.5 mg prednisolone daily for 2 years, the P-group, or no prednisolone, the NoP-group, OPG and RANKL were analysed at 0-24 months and 1CTP and CTX-1 at 0-12 months. Radiographs of hands and feet were assessed at 0, 1 and 2 years using the modified Sharp-van der Heijde score and radiological progression defined as increase in total Sharp score above 5.8. Data were analysed with a mixed linear model and by the GENMOD procedure. RESULTS: In the P-group, RANKL and the ratio OPG/RANKL were stable between baseline and 24 months, whereas in the NoP-group, RANKL increased and the ratio OPG/RANKL decreased. CTX-1 decreased significantly more in the P-group. 1CTP decreased over time in both groups, but more in the P-group, P < 0.001, a difference also present in the subgroups of patients in remission. The decrease in 1CTP was associated with less radiological progression after 2 years and displayed a significant interaction with treatment. CONCLUSION: Low-dose prednisolone may inhibit progression of joint destruction by interfering with MMP activity, seen as a marked decrease in 1CTP, as well as by impairing osteoclast activation, shown by a stable OPG/RANKL ratio.
21792838 Nerve growth factor: A key local regulator in the pathogenesis of inflammatory arthritis. 2011 Nov OBJECTIVE: The effect of nerve growth factor (NGF) and its receptor (NGFR) in inflammatory diseases is a novel research field. The purpose of this study was to investigate the role of NGF/NGFR in human T cell subpopulations and fibroblast-like synovial cells (FLS) and examine its pathophysiologic significance in psoriatic arthritis (PsA) and rheumatoid arthritis (RA). METHODS: Expression of NGF/NGFR was examined in synovial fluid (SF), FLS, peripheral blood (PB)-derived T cells, and SF-derived T cells from patients with PsA, RA, and osteoarthritis (OA). NGF levels were determined by enzyme-linked immunosorbent assay. NGF-induced T cell/FLS proliferation was examined by MTT assay. Low-affinity (p75)/high-affinity (TrkA) NGFR expression was determined by high-dimensional fluorescence-activated cell sorting. A monochlorobimane assay was used to determine the effect of NGF on T cell survival. RESULTS: Levels of NGF were higher in SF samples from PsA and RA patients as compared to SF samples from OA patients. NGF-induced FLS proliferation was more marked in PsA and RA patients. TrkA was up-regulated on activated SF T cells from PsA (mean ± SD 22 ± 6.2%) and RA (8 ± 1.3%) patients, whereas in SF samples from OA patients, TrkA+CD3+ T cells were not detectable. NGF induced the proliferation of PB T cells, induced the phosphorylation of Akt in activated T cells, and consistent with known pAkt activity, inhibited tumor necrosis factor α-induced cell death in these T cells. CONCLUSION: Based on our findings, we propose a model in which NGF secreted by FLS into PsA and RA synovium promotes the survival of activated autoreactive T cells as well as FLS proliferation. Thus, NGF has the potential to sustain the chronic inflammatory cascades of arthritis of autoimmune origin.
22901757 Atorvastatin inhibits osteoclastogenesis by decreasing the expression of RANKL in the syno 2012 Aug 17 INTRODUCTION: Statins, hydroxymethylglutaryl-coenzyme A reductase inhibitors, have been reported to have antiinflammatory and/or immunomodulatory effects and prophylactic and therapeutic effects in collagen-induced arthritis, an experimental model of rheumatoid arthritis (RA). The authors undertook to determine the effect of atorvastatin on the expressions of osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) in RA fibroblast-like synoviocytes (FLSs), to identify the mechanisms responsible for these effects, and to determine whether the statin inhibits osteoclastogenesis. METHODS: FLSs isolated from five RA patients were cultured in the presence of 20 ng/ml of tumor necrosis factor-α (TNF-α) with or without atorvastatin. RANKL expressions were assayed with Western blotting and enzyme-linked immunosorbent assay. RANKL, RANK, and OPG expression were assayed with reverse transcription-polymerase chain reaction (RT-PCR). Osteoclast formation was assayed by counting cells after staining for tartrate-resistant acid phosphatase in cocultures of peripheral blood mononuclear cells (PBMCs) and RA FLSs. RESULTS: Atorvastatin inhibited the expression of RANKL in RA FLSs in a dose-dependent manner, and the suppression of RANKL was prevented by mevalonate. However, OPG expression was not affected by atorvastatin in RA FLSs, and atorvastatin did not affect RANK expression in CD14⁺ cells. Conversely, atorvastatin suppressed TNF-α-induced p38 phosphorylation in RA FLSs and significantly reduced TRAP-positive multinucleated osteoclast formation in the coculture of PBMCs and RA FLSs. CONCLUSION: These results suggest that atorvastatin inhibits osteoclastogenesis and bone destruction in RA patients.
22351097 K/BxN serum transfer arthritis as a model of inflammatory joint pain. 2012 In this chapter, we describe the usage of this rheumatoid arthritis model to investigate pain-like behavior in mice, including the assessment of clinical changes and the time-dependent changes in nociceptive behavior during disease progresses.
23223014 Whole-genome detection of disease-associated deletions or excess homozygosity in a case-co 2013 Mar 15 Unlike genome-wide association studies, few comprehensive studies of copy number variation's contribution to complex human disease susceptibility have been performed. Copy number variations are abundant in humans and represent one of the least well-studied classes of genetic variants; in addition, known rheumatoid arthritis susceptibility loci explain only a portion of familial clustering. Therefore, we performed a genome-wide study of association between deletion or excess homozygosity and rheumatoid arthritis using high-density 550 K SNP genotype data from a genome-wide association study. We used a genome-wide statistical method that we recently developed to test each contiguous SNP locus between 868 cases and 1194 controls to detect excess homozygosity or deletion variants that influence susceptibility. Our method is designed to detect statistically significant evidence of deletions or homozygosity at individual SNPs for SNP-by-SNP analyses and to combine the information among neighboring SNPs for cluster analyses. In addition to successfully detecting the known deletion variants on major histocompatibility complex, we identified 4.3 and 28 kb clusters on chromosomes 10p and 13q, respectively, which were significant at a Bonferroni-type-corrected 0.05 nominal significant level. Independently, we performed analyses using PennCNV, an algorithm for identifying and cataloging copy numbers for individuals based on a hidden Markov model, and identified cases and controls that had chromosomal segments with copy number <2. Using Fisher's exact test for comparing the numbers of cases and controls with copy number <2 per SNP, we identified 26 significant SNPs (protective; more controls than cases) aggregating on chromosome 14 with P-values <10(-8).
22751591 Dynamic contrast-enhanced magnetic resonance imaging of articular and extraarticular synov 2012 Jul OBJECTIVE: Dynamic, contrast-enhanced magnetic resonance imaging (DCE-MRI), the quantification of enhancement within the synovial membrane and bone by extracting curves using fast T1-weighted sequences during intravenous administration of contrast agent, evaluates synovitis and bone marrow edema in psoriatic arthritis (PsA). In this pilot study, we looked at possible differences between joint synovitis and tenosynovitis in PsA as compared with rheumatoid arthritis (RA). METHODS: Seven patients with PsA and 10 with RA were studied. After DCE-MRI was performed on 3 axial slices of the wrist, the enhancement ratio was calculated on 6 different regions of interest (ROI) of the synovial membrane outlined by the operator: the wrist compartment, 3 extensor tendon compartments, and 2 flexor compartments. DCE-MRI results were quantitatively analyzed using the Dynamika software, a computer-aided semiautomated method. RESULTS: In PsA, the area of the ROI outlined around the first and second extensor compartments was larger than in RA; the opposite was true for the extensor carpi ulnaris region. The volume of inflammation was significantly higher in RA than in PsA for all the extensor compartments except the second, and in the joint synovial membrane. The DCE-MRI indicators of the degree of inflammation were higher for PsA in the joint synovial membrane (p = 0.002 and p < 0.001, respectively). There was a significant correlation between volume of inflammation but not its degree and 28-joint Disease Activity Score at the level of the wrist joint (r = 0.6; p = 0.01). CONCLUSION: DCE-MRI can reveal useful and potentially clinically important information on the characteristics of different types of arthritis.
22996324 Herbal medicine for rheumatic diseases: promises kept? 2012 Dec Traditional healers throughout the world have relied on herbal medicines in their practices for millennia to treat a wide array of conditions, including arthritis. Present-day patients continue to seek care from complementary and alternative providers and more effective and less toxic treatments. A broad foundation of laboratory studies suggests that many herbal products have pertinent medicinal effects for the management of diseases like osteoarthritis and rheumatoid arthritis. However, few high quality clinical trials have yet been carried out to substantiate the safety and efficacy of herbal medicines. Some of the best research to date in this area is summarized in this review.
21391428 Dermatologic adverse events: golimumab, friend or foe? 2011 Jan Golimumab is a fully human anti-TNF-alpha blocker that has demonstrated its efficacy in the treatment of numerous kinds of diseases. Although it is generally safe and well tolerated, various adverse events have been reported. The present aim is to improve the understanding of dermatologic adverse events associated with golimumab following a search of various scientific databases. This systematic review and meta-analysis shows that golimumab is associated neither with severe injection-site reactions nor with injection-site erythema. We found no significant lupus-like syndromes, and no significant skin squamous cell carcinoma. We further suggest systematic dermatologic monitoring in clinical practice during golimumab therapy. Subsequent research should employ a larger cohort of patients to ensure clear and significant future conclusions.
22096433 Conical, radiographic, and patient-reported results of surface replacing proximal interpha 2011 The purpose of this study was to evaluate the one-year clinical, radiologic and patient-reported results of surface-replacing proximal interphalangeal joint arthroplasty (SR-PIP) of the hand. Fifteen patients with 18 joints underwent the procedure, and nine patients with 11 joints had follow-up of at least one year's duration. Of these joints, six had a diagnosis of osteoarthritis with no history of trauma, three had post-traumatic arthritis, one had psoriatic arthritis, and one had erosive arthritis. The mean clinical follow-up was at 3.3 years, and the mean radiographic follow-up was at 3.1 years. The average post-operative gain in range of motion at the PIP joint was 28 degrees and was statistically significant. Six patients completed self-reported questionnaires at a mean of 4.8 years post-operatively. The mean Disabilities of the Arm, Shoulder and Hand (DASH) score post-operatively was 17, and the Michigan Hand Questionnaire (MHQ) score for overall satisfaction was 70. There were three complications but only one reoperation. Seven of 11 joints showed some evidence of subsidence on follow-up radiographic examination. However, no joints were revised secondary to loosening. Longer follow-up is needed to determine if this observable radiologic subsidence leads to symptomatic loosening of the implant.
22005949 Wnt signaling genes of murine chromosome 15 are involved in sex-affected pathways of infla 2012 Apr OBJECTIVE: Sex disparities in rheumatoid arthritis (RA) are well documented despite the lack of any known major RA susceptibility genes mapped to sex chromosomes. Murine chromosome 15 carries the sex-affected Pgia8 locus that mediates proteoglycan-induced arthritis, and homologous human loci are associated with RA. This study was undertaken to identify genes/mechanisms implicated in sex disparities in arthritis. METHODS: Gene expression analysis was performed using RNA isolated from the paws of male and female Pgia8-congenic mice with collagen antibody-induced arthritis. Results were corroborated by reverse transcription-polymerase chain reaction, and mice were also studied prior to disease onset. Ingenuity Pathways Analysis of the expression patterns and gene functions was used to discover locus-specific and sex-affected signature transcripts. RESULTS: We found that the Pgia8 locus regulates antibody-mediated inflammatory arthritis differently in males and females. In Pgia8-congenic males, arthritis severity was 30% less (P < 0.005) than in wild-type males, but the antiinflammatory effect was similar in wild-type and congenic females. Transcriptome analysis indicated that 12 genes within the locus were significantly dysregulated in arthritic joints of congenic mice; expression of these genes was also sex specific. The genes that correlated most highly with arthritis severity included those for collagen triple-helix repeat-containing 1 (Cthrc1), metalloproteinase (Adamts12), R-spondin (Rspo2), and syndecan (Sdc2) (r = 0.87-0.91). The level of Cthrc1 message also correlated with that of the genes for the proinflammatory cytokines interleukin-1β and interleukin-6. CONCLUSION: These results indicate that sex-specific disparities in RA are linked to transcriptional regulation of genes involved in cartilage degradation (Adamts12) and canonical and noncanonical Wnt signaling (Cthrc1, Rspo2, Sdc2).
22772460 Management of rheumatoid arthritis: the 2012 perspective. 2013 Jan Management of rheumatoid arthritis (RA) has improved over the last 10 years. These changes have been monitored in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) observational cohort, and clinical remission has become a realistic goal. However, we should recognize that the ultimate goal of treatment is to improve long-term outcomes. These improvements have been achieved not only by new drugs, but also by the overall approach toward treating patients. Biologics in RA have been successful; however, safety concerns and pharmacoeconomical issues are still debated. Protein kinase inhibitors have been developed, and can be called "molecular-targeting antirheumatic drugs" (MTARDs), as opposed to "disease-modifying antirheumatic drugs." In comparison with biologics, oral MTARDs should be less expensive; however, their safety profile should be confirmed. Considering the limitations of randomized trials, it is encouraged to conduct studies based on daily practice. It is time to consider the application of the evidence generated from "our" patients to patients in daily practice, namely institute-based medicine as opposed to evidence-based medicine, of which "IORRA-based medicine" would be representative. Finally, there remains much for us rheumatologists to do for our patients, including patient-perspective approaches.
21455248 Rheumatoid arthritis: International disparities in access to anti-TNF therapy. 2011 Apr The establishment of new benchmarks for treatment outcomes promises to drive great advances in rheumatoid arthritis therapy, but data on ‘real life’ experience with biologic therapy demonstrate that geographic location influences the stage of disease at which these agents are initiated.
20889596 Arsenic trioxide induces apoptosis of fibroblast-like synoviocytes and represents antiarth 2011 Jan OBJECTIVE: recent studies have demonstrated that rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) proliferate as fiercely as tumor cells. Induction of apoptosis in RA FLS therefore provides a new approach for the inhibition of joint destruction. Arsenic trioxide (As(2)O(3)) was reported to be an effective apoptosis inducer in a variety of cell types. We investigated the possible effect of As(2)O(3) on apoptosis induction of RA FLS and the mechanisms involved in this process. METHODS: apoptosis was determined by flow cytometric analysis, terminal deoxynucleotide transferase-mediated dUTP nick end-labeling, and transmission electron microscopy. The activity and messenger RNA (mRNA) expression of nuclear factor-κB (NF-κB) was then detected by ELISA and real-time polymerase chain reaction, respectively. Activities of caspase-3 and caspase-8 were evaluated using luminogenic substrates. The effect of As(2)O(3) on the morphology of rats with collagen-induced arthritis was evaluated under a light microscope after H&E staining. RESULTS: as(2)O(3) significantly enhanced the apoptosis of RA FLS. It suppressed the DNA-binding activity and mRNA expression level of NF-κB, probably by inhibiting tumor necrosis factor-α-induced activation of NF-κB. As(2)O(3) treatment significantly increased the activity of both caspase-3 and caspase-8. Morphological analysis revealed histological recovery in the synovial membrane. Synovial hyperplasia and inflammation in the joints were effectively inhibited. CONCLUSION: as(2)O(3) represents an apoptotic effect on RA FLS through NF-κB signaling pathway, and this process is mediated by the activation of caspase cascade. Treatment with As(2)O(3) significantly improved the pathologic changes of collagen-induced arthritis and may have potential for treatment of RA.
22012422 [Influence of reproductive factors in the clinical and laboratory parameters of rheumatoid 2011 Jul PURPOSE: To study if rheumatoid arthritis (RA) is influenced by age at menarche, number of pregnancies and reproductive life span. METHODS: This was a cross-sectional and retrospective study of medical records of 247 RA patients. We collected data on menarche, menopause, number of pregnancies, autoantibodies, serositis, rheumatoid nodules, and functional index of Steinbrocker. Association studies were done using the Student t and Mann-Whitney tests and correlation was determined by the Pearsonand Spearman tests. The level of significance adopted was 5%. RESULTS: The mean age at diagnosis of RA was 43.2±14.1 years, the median age at menarche was 13 years and the median number of pregnancies was 3. Rheumatoid factor was present in 63.9% of the patients, 20% had antinuclear factor, 8.8% rheumatoid nodules, 2.8% had pleural effusion, and 2.4% had pericarditis. The Steinbrocker functional index showed that 45.6% had a score of 1, 40.8% a score of 2, 3 score of 9.1, and 4.3% a score of 4. We found an inverse correlation between the number of pregnancies and age at onset of RA (p CONCLUSION: A precocious menarche and brief reproductive life indicate a poor prognosis regarding pleurisy. A larger number of pregnancies and late menopause show a protective effect, delaying the onset of the disease.
22467933 Longterm retention of tumor necrosis factor-α inhibitor therapy in a large italian cohort 2012 Jun OBJECTIVE: To evaluate 4-year retention rates of tumor necrosis factor-α (TNF-α) inhibitors adalimumab, etanercept, and infliximab among patients with longstanding rheumatoid arthritis (RA), as derived from an Italian national registry. METHODS: The clinical records of 853 adult patients with RA in the GISEA (Gruppo Italiano Studio Early Arthritis) registry were prospectively analyzed to compare drug survival rates and the baseline factors that may predict adherence to therapy. RESULTS: In 2003 and 2004, 324 patients started treatment with adalimumab, 311 with etanercept, and 218 with infliximab. After 4 years, the global retention rate of anti-TNF-α therapy was 42%. Etanercept survival (51.4%) was significantly better than that of infliximab (37.6%) or adalimumab (36.4%; p < 0.0001). Accordingly, the mean duration of therapy was significantly longer for etanercept (3.1 ± 2 yrs) than for adalimumab (2.6 ± 2 yrs) or infliximab (2.7 ± 2 yrs; p < 0.05). The use of concomitant disease-modifying antirheumatic drugs, mainly methotrexate, and the presence of comorbidities significantly predicted drug continuation (p < 0.01), whereas a high Disease Activity Score did not. CONCLUSION: The 4-year global drug survival of adalimumab, etanercept, and infliximab was lower than 50%, with etanercept having the best retention rate. The main positive predictor of adherence to anti-TNF-α therapy was the concomitant use of methotrexate. Our study provides further evidence that the real-life treatment of patients with RA may be different from that of randomized clinical trials.
22018185 Glucocorticoids in rheumatoid arthritis: lessons from the Utrecht study. 2011 Sep The lessons from the Utrecht study on glucocorticoid therapy in early rheumatoid arthritis and of the spin-off and follow-up studies are reviewed. The data indicate that: glucocorticoids are DMARDs, the joint-sparing effect is predominantly on erosions, glucocorticoids do not influence the percentage of patients developing erosive disease, and the gain in joint-sparing effect persists after the stop of treatment. Further lessons are that the size of the joint-sparing effect and the (presumed) size of the symptomatic effect of glucocorticoids depend on co-therapies. Additional DMARDs must be added to glucocorticoids for maximum effect on radiographic progression. Finally, low-dose glucocorticoids are safer than often thought.
22132693 Post-transcriptional regulation of IL-6 production by Zc3h12a in fibroblast-like synovial 2011 Nov OBJECTIVES: Zc3h12a is an RNA binding protein with a CCCH-type finger motif and is known to regulate mRNA metabolism. Previous reports suggest that Zc3h12a acts as a negative regulator of inflammatory processes because it is involved in the degradation of IL-6 mRNA. We investigate the effect of Zc3h12a on IL-6 production in fibroblast-like synovial cells (FLS) from rheumatoid arthritis (RA) patients. METHODS: The expression of Zc3h12a in FLS was determined by polymerase chain reaction. To knock down Zc3h12a expression in FLS, siRNA for Zc3h12a was transfected by the lipofection method. The supernatants were collected after siRNA transfection for the quantification of IL-6 production. The phosphorylation of the signal transducer and activator of transcription 3 (STAT3) was examined by Western blotting. Cell proliferation was analysed by the Cell Counting Kit-8 assay after Zc3h12a knockdown. RESULTS: mRNA for Zc3h12a were demonstrated in FLS from RA patients. Zc3h12a transcripts were induced by LPS or IL-1β in FLS. The production of IL-6 as well as its mRNA expression was significantly increased by the Zc3h12a knockdown. The Zc3h12a knockdown also induced the activation of STAT3, which the anti IL-6 receptor antibody inhibited. Proliferation of Zc3h12a-knockdown FLS increased significantly in the presence of recombinant soluble IL-6 receptor (sIL-6R). CONCLUSIONS: Our data suggest that Zc3h12a is a novel IL-6 regulator in FLS, which may be involved in the progression of RA.
22696440 Retinoic acid attenuates rheumatoid inflammation in mice. 2012 Jul 15 Retinoic acid is the active vitamin A derivative and is well-known to have diverse immunomodulatory actions. In this study, we investigated the impact of all-trans retinoic acid (ATRA), a biologic key metabolite of vitamin A, on the development of arthritis and the pathophysiologic mechanisms by which ATRA might have antiarthritic effects in animal model of rheumatoid arthritis (RA; collagen-induced arthritis [CIA] in DBA/1J mice). We showed that treatment with ATRA markedly suppressed the clinical and histologic signs of arthritis in the CIA mice. It reduced the expression of IL-17 in the arthritic joints. Interestingly, Foxp3(+) regulatory T cells were markedly increased and IL-17-producing CD4(+) T cells (Th17 cells) were decreased in the spleens of ATRA-treated mice. In vitro treatment with ATRA induced the expression of Foxp3 and repressed the IL-17 expression in the CD4(+) T cells in mice. ATRA suppressed the production of total IgG and IgG2a in splenocytes that were stimulated by LPS. It also reduced serum levels of total IgG and IgG2 anti-collagen Abs and germinal center formation in CIA mice. In addition, the ATRA-treated mice showed decreased osteoclast formation in arthritic joints. Moreover, ATRA downregulated the expression of receptor activator of NF-κB ligand, the leading player of osteoclastogenesis, in the CD4(+) T cells and fibroblast-like synoviocytes from patients with RA. Furthermore, ATRA prevented both human monocytes and mice bone marrow-derived monocytes/macrophage cells from differentiating into osteoclasts. These data suggest ATRA might be an effective treatment modality for RA patients.
22395503 IL-17 patterns in synovium, serum and synovial fluid from treatment-naïve, early rheumato 2012 BACKGROUND: There are actually becoming controversial data regarding the profiles of interleukin-17 (IL-17) in different pathogenical stages of rheumatoid arthritis (RA). OBJECTIVES: To assessing the IL-17 patterns in synovium, serum and synovial fluid from treatment-naïve early RA patients and to identifying potential correlations with disease activity markers and with synovial histopathological profile. MATERIALS AND METHODS: Serum samples from 30 treatment-naïve early RA patients were evaluated for C-reactive protein (CRP), erythrocytes sedimentation rate (ESR), rheumatoid factor (RF), anti-cyclic citrullinated peptide antibodies (anti-CCP). IL-17A levels were also assessed in serum and synovial fluid (SF). Disease activity score (DAS28) calculation was done for all patients. Control serum and SF samples were obtained from 29 patients with osteoarthritis (OA); control synovium specimens were obtained from eight patients with OA and during surgery for knee tear ligaments. Histopathological (Hp) score, immunohistochemical reactivity for IL-17 were also assessed in synovium of early RA patients and controls. Dependencies between serum and synovial profile of IL-17A and the other parameters were statistically tested. RESULTS: In early RA patients, strong correlations of serum and SF IL-17A levels were found with ESR, CRP, RF, anti-CCP, Hp score and IL-17 synovial immunoreactivity; a good correlation was noted with DAS28 score. Also, strong correlation was noted between serum and SF IL-17A levels. CONCLUSIONS: In early stages of untreated RA, simultaneous IL-17 assessment of serum, SF and synovium might be valuable in defining activity and predictive patterns, given that synovium is highly suggestive for an disease aggressivity and might express specific therapeutically targets.