Patients with AS had higher levels of OPN compared with controls. The plasma OPN level was correlated with serum ALP, OCN and CTX-I levels, but not with disease activity in AS. OPN might be involved in bone remodelling rather than in inflammation in AS.

Serum levels of TWEAK were significantly elevated in patients with RA, and reflected disease activity and short-term response to etanercept treatment.

BackgroundLBEC0101 is a newly developed biosimilar of etanercept (ETN). As rheumatoid arthritis (RA) treatment is a long-standing process in the clinical practice, the long-term safety and efficacy of anti-TNF inhibitors have been studied and reported.1 Clinical studies have been conducted to evaluate the efficacy and safety of biosimilar after switching from their originator drug.2 ObjectivesTo evaluate the long-term efficacy, safety, and immunogenicity of switching from the ETN reference product (RP) to LBEC0101 or continuing LBEC0101 in patients with RA.MethodsThis multicenter, single-arm, open-label extension study enrolled patients with RA who had completed the 52 week treatment period of the randomised, double-blind, parallel-group, Phase III study for LBEC0101 (NCT02357069). Patients who were deemed requiring continuous treatment for RA upon the investigator’s discretion and agreed to participate in this study were allowed for participation. All patients received LBEC0101 50 mg/ml once a week for 48 weeks with the stable dose of methotrexate regardless of the randomization group in the Phase III study. Efficacy, safety and immunogenicity were assessed up to Week 100. Data were analysed for patients who continued to receive LBEC0101 for 100 weeks (maintenance group) and for those who had received ETN-RP for 52 weeks and then switched to LBEC0101 for 48 weeks (switch group).ResultsA total of 148 patients were enrolled in this study; 70 patients continued to receive LBEC0101 and 78 patients switched to receive LBEC0101 from ETN-RP. DAS28-ESR score in the full analysis set were maintained in both groups from week 52 through week 100 (from 3.068 to 3.103 in maintenance group vs. from 3.161 to 3.079 in switch group). Response rates at week 100 for maintenance and switch groups, respectively, were 79.7% vs. 83.3% for ACR20, 65.2% vs. 66.7% for ACR50% and 44.9% vs. 42.3% for ACR70. The incidences of adverse events were comparable between the groups (70.0% for maintenance group and 70.5% for switch group, respectively). The proportion of patients who newly developed antidrug antibodies was similar between the groups (1.4% for maintenance group and 1.3% for switch group, respectively).ConclusionsThe efficacy and safety of LBEC0101 were comparable in both maintenance and switch groups. The efficacy of LBEC0101 was well sustained over 100 weeks.References[1] Weinblatt ME, Bathon JM, Kremer JM, et al. Safety and efficacy of etanercept beyond 10 years of therapy in North American patients with early and longstanding rheumatoid arthritis. Arthritis Care Res (Hoboken)2011;63:373–82.[2] Emery P, Vencovský J, Sylwestrzak A, et al. Long-term efficacy and safety in patients with rheumatoid arthritis continuing on SB4 or switching from reference etanercept to SB4. Ann Rheum Dis2017 [Epub ahead of print].AcknowledgementsHanJoo Baek, HoonSuk Cha, JungYoon Choe, ChanBum Choi, InAh Choi, SeungJae Hong, JinWuk Hur, GeunTae Kim, HyunAh Kim, Jinseok Kim, Jisoo Lee, SangHeon Lee, SangIl Lee, SeungGeun Lee, ShinSeok Lee, YunJong Lee, Ju...

BackgroundNucleotide-binding and oligomerization domain NOD-like receptors (NLRs) have been associated with several human diseases including infections, malignancies, and inflammatory disorders. These innate immune pattern recognition molecules paly critical roles in innate immunity and inflammation. Some inflammasome-forming NLRs including NLRP1, NLRP2, NLRP3, NLRC4, NLRC5, NLRP6, and NLRP7, can induce the activation of mitogen-activated protein kinase and the transcription factor NF-κB. A different set of NLRs, such as NLRP12, NLRX1, and NLRC3, negatively regulate diverse biological pathways associated with inflammation.ObjectivesThis study was performed to determine the expression pattern of NLRs in rheumatoid synovium and to investigate whether their regulation can influence the inflammatory response in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA).MethodsWe explored the expression of several inflammasome-forming and -nonforming NLRs, including NLRP1, NLRP2, NLRP3, NLRC5, NLRX1, and NLRC3, in synovium obtained from patients with RA and patients with osteoarthritis (OA) by immunohistochemistry. The expression of NLRs was also studied in FLS derived from joint tissues of RA patients and OA patients using real time RT-PCR. RNA interference (RNAi) plasmids for NLRs were transfected to abrogate specific NLR expression in RA FLS, and adenovirus containing the NLR transcript was delivered into RA FLS to strengthen its gene expression. Levels of pro-inflammatory genes and their protein products were determined using real-time RT-PCR and ELISA in RA FLS.ResultsBy immunohistochemistry and real time RT-PCR, we were unable to distinguish RA from OA synovium on the basis of their level of RNA expression and protein production of NLRP2, NLRP3, NLRC5, and NLRX1. In synovial tissues from RA patients, NLRC1 was not detected, though RA FLS contained higher levels of NLRP1 compared to OA FLS. NLRC3 expression was detected at the RNA and protein levels in RA synovium and FLS, but its levels were much lowered that those from OA samples. Gene expression and production of IL-1β, IL-6, chemokine ligand 2 (CCL-2), CCL-7, cyclooxygenase 2 and MMP-9 were markedly increased in NLRC3 RNAi plasmid-transfected RA FLS, while transfection with adenoviral vectors encoding NLRC3 induced reductions in those levels.ConclusionsNLRC3 is down-regulated in RA synovium and the regulation of its expression showed anti-inflammatory activity in RA FLSs. These findings provide evidence for the anti-inflammatory effect of NLRC3 in RA.ReferencesWen H, Miao EA, Ting JP. Mechanisms of NOD-like receptor-associated inflammasome activation. Immunity 2013; 39: 432–41.Sidiropoulos PI, Goulielmos G, Voloudakis GK, Petraki E, Boumpas DT. Inflammasomes and rheumatic diseases: evolving concepts. Ann Rheum Dis 2008; 67: 1382-9.Schneider M, Zimmermann AG, Roberts RA, Zhang L, Swanson KV, Wen H, et al. The innate immune sensor NLRC3 attenuates Toll-like receptor signaling via modification of the signaling adaptor TRAF6 and transcription ...

BackgroundChondrocalcin, c-terminal of type II procollagen peptide, plays a major part in ossification processes by acting as a nucleation core of matrix calcification. Chondrocalcin and its related growth factors can also influence tendon and ligament formation and appear to be a key molecular pathway involved in this pathological cascade.ObjectivesThe purposes of this study were to evaluate the association of chondrocalcin in the pathogenesis of inflammation and calcification in an animal model of ankylosing spondylitis.MethodsPeripheral arthritis was induced by transferring the HLA-B2704 gene into male Kunming mice and their inflamed hid paw joints sections were obtained. Chondrocalcin was detected using real time-PCR and anti-chondrocalcin antibody developed from proteins occurred from C-terminal amino acid sequence of type II collagen. Immunohistochemical staining and western blot assay were performed to identify the expression and localization of chondrocalcin in joint sections of the animal model.ResultsOn immunohistochemistry, chondrocalcin was detected in inflamed joint tissues of animal models and this was more densely distributed in spindle-shaped fibroblast-like cells and hypertrophic chondrocytes. Chondrocalcin production was increased in hind paw joints of animal model compared to empty vector-injected mice and its mRNA expressions were also increased peripheral blood mononuclear cells from animal model compare to empty vector-injected mice.ConclusionsThis study showed that chondrocalcin can be detected in inflammed tissues of animal models of AS and that the levels of condrocalcin productions and its gene expressions are increased in animal models. These results can provide an evidence for the role of chondrocalcin in pathogenesis of AS.ReferencesPoole AR, Pidoux I, Reiner A, Choi H, Rosenberg LC. Association of an extracellular protein (chondrocalcin) with the calcification of cartilage in endochondral bone formation. J Cell Biol 1984; 98(1): 54-65.Hinek A, Reiner A, Poole AR. The calcification of cartilage matrix in chondrocyte culture: studies of the C-propeptide of type II collagen (chondrocalcin). J Cell Biol 1987; 104(5): 1435-41.Kondoh T, Hamada Y, Iino M, Takahashi T, Kikuchi T, Fujikawa K, Seto K. Regional differences of type II collagen synthesis in the human temporomandibular joint disc: immunolocalization study of carboxy-terminal type II procollagen peptide (chondrocalcin). Arch Oral Biol 2003; 48(9): 621-5.Disclosure of InterestNone declared