The Role of microRNA-146a (miR-146a) and its Target IL-1R-Associated Kinase (IRAK1) in Psoriatic Arthritis Susceptibility

2010 ◽  
Vol 71 (5) ◽  
pp. 382-385 ◽  
Author(s):  
A. Chatzikyriakidou ◽  
P. V. Voulgari ◽  
I. Georgiou ◽  
A. A. Drosos
2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1633.1-1633
Author(s):  
D. Cici ◽  
C. Rotondo ◽  
A. Corrado ◽  
S. Berardi ◽  
N. Mansueto ◽  
...  

Background:Occasional findings of anti-citrullinated-protein-antibodies (ACPA) and anti-nuclear-antibodies (ANA) were rarely described in literature on Psoriatic Arthritis (PsA) and on Spondyloarthritis (SpA) in general. How these autoimmune dysregulations can affect the course of them is not yet understood.Objectives:The aim of our study is to evaluate if the presence of ACPA and ANA can determine different disease subsets and influence the DMARDs monotherapy (methotrexate) drug survival (DSM) and b-DMARDs multi-failure patients (MF).Methods:We conducted a retrospective study on patients with Psoriatic Arthritis (PsA) and Spondyloarthritis that fulfilled the ASAS and CASPAR criteria. Patients with diagnosis of connective tissue disease and rheumatoid arthritis and patients ≤ 18 years old were excluded from the study. For each patient, the following variables were considered: age, ACPA, ANA, time between arthritis onset and start of DMARDs (start-time), DSM, switch to b-DMARDs (sw-bDMARDs), arthritis subset (oligoarticular (OA), polyarticular (PA), enthesitis (EA), axial involvement (AI)), number of comorbidities (NC), Charlson Comorbidity Index (CCI).Results:150 patients (55% with PsA and 45% with another SpA) were included in the study. No differences were found in age, ANA rate, ACPA rate, start-time, OA, PA, EA, AI, NC and CCI between the PsA and SpA groups.In the whole group of patients, the ACPA+ subjects(11%) had a significant increase of NC (2.47 ± 1.5 vs 1.6 ± 1.4, p=0.035), a trend to higher CCI, to switch to b-DMARDs, and to be MF compared to those without ACPA. In the same group, the ANA+ patients (12%) showed shorter DSM (233.5 wk ± 45.9 vs 548.0 wk ± 56.8, p=0.362) with similar trend in each subgroup (PsA and SpA).In SpA group, the ACPA+ patients(6,3%) had a trend to shorter DSM (269.0 weeks ± 125vs 603.96 wk± 92.8, p=0.492),to higher sw-bDMARDs, and to be MF, higher NC and CCI compared to those without ACPA. No differences in clinical subset (OA, PA, EA, AI) were observed. In the same group the ANA+ patients had significant higher rate of PA (100% vs 65%, p=0.026) rather than OA (0% vs 35%, p=0.025). No significant differences were found in NC, CCI, MF.In the PsA group, ACPA+ patients showed a trend to develop PA and EA subsets, shorter DSM (187.5 wk ± 48.7 vs 299.6 wk ± 31.4, p=0.415), higher rate to sw-bDMARDs and to be MF. The ANA+ PsA patients had higher trend to develop PA and AI subsets rather than OA and EA. All ANA+ patients were MF (100% vs 42%, p=0.046).Conclusion:The ACPA and ANA positivity in PsA and SpA patients could be suggestive of more severe clinical disease manifestation, higher frequency of comorbidities and lower predicted 10-year survival (CCI). Moreover, this autoimmune dysregulation could be associated with worse drug survival in monotherapy with methotrexate and higher chance to be MF. Therefore, they can be taken into account for clinical management of these patients.Disclosure of Interests:None declared


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1307.1-1308
Author(s):  
E. Siniauskaya ◽  
T. Kuzhir ◽  
V. Yagur ◽  
R. Goncharova

Background:Rheumatoid arthritis (RA) is a chronic systemic disorder of the connective tissue of still unknown aetiology and complex autoimmune pathogenesis that primarily affects small joints. HLA alleles provide for 11-37% of the RA heritability, suggesting the substantial role of the non-HLA loci in genetic predisposition to RA. Among non-HLA loci,IL6, IL6RandSTAT4genes attract attention, however, the data concerning their influence on RA risk are somewhat contradictory.Objectives:The aim of the study was to analyze the involvement of four SNPs (STAT4rs7574865,IL6rs1800795,IL6Rrs2228145 and rs4845618) in RA susceptibility.Methods:187 patients diagnosed with RA (mean age 58.2 ± 11.9), and 380 healthy blood donors (mean age 37.18 ± 10.69 years) were included into the study. DNA extraction from peripheral blood samples was performed using the phenol-chloroform method. SNPs were genotyped using the real-time PCR with fluorescent probes. The allele and genotype frequencies were compared using the χ2 test. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using the VassarStats online tool.Results:Utilizing recessive genetic model we found an association between TT genotype ofSTAT4rs7574865 (OR = 2.362; 95%CI [1.0378 – 5.376], p = 0.038) and RA. ForIL6rs1800795, it was found that CC genotype had significantly higher frequency among patients with rheumatoid arthritis as compared to that in controls (OR = 1.52; 95%CI [1.02 – 2.27], p = 0.0456). No associations ofIL6Rrs2228145 and rs4845618 SNPs with risk of RA were found in the total group of patients vs. controls. It was also shown thatIL6rs1800795 CC genotype frequency was significantly higher among the patients with RF-negative status (p = 0.0019).Conclusion:Thus, we provide evidence for association of theSTAT4rs7574865 andIL6rs1800795 variants with risk of RA in the Belarusian population, some features of interplay being revealed between gene polymorphisms analyzed and RA antibody status. Abovementioned SNPs may contribute to RA genetic susceptibility in the Belarusian population.Disclosure of Interests:None declared


2013 ◽  
Vol 73 (1) ◽  
pp. 132-137 ◽  
Author(s):  
Karen Minde Fagerli ◽  
Elisabeth Lie ◽  
Désirée van der Heijde ◽  
Marte Schrumpf Heiberg ◽  
Åse Stavland Lexberg ◽  
...  

2013 ◽  
Vol 40 (8) ◽  
pp. 1434-1437 ◽  
Author(s):  
April W. Armstrong ◽  
Joel M. Gelfand ◽  
Wolf-Henning Boehncke ◽  
Ehrin J. Armstrong

At the 2012 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) in Stockholm, Sweden, several GRAPPA members led a panel discussion on cardiovascular (CV) comorbidities of psoriasis and psoriatic arthritis (PsA). The panelists discussed the role of insulin resistance in the pathophysiology of psoriasis, the possible effect of tumor necrosis factor inhibitors on CV comorbidities, and the effect of 12/23 monoclonal antibodies on CV outcomes. The panelists also addressed how lessons from CV comorbidity research could be applied to other areas of comorbidity research in psoriasis and PsA and identified future research directions in this area.


2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Zhen-Zhen Wang ◽  
Hong-Sheng Wang
Keyword(s):  

2022 ◽  
Vol 23 (2) ◽  
pp. 921
Author(s):  
Shang-Hung Lin ◽  
Ji-Chen Ho ◽  
Sung-Chou Li ◽  
Yu-Wen Cheng ◽  
Chung-Yuan Hsu ◽  
...  

Psoriatic arthritis (PsA) results from joint destruction by osteoclasts. The promising efficacy of TNF-α blockage indicates its important role in osteoclastogenesis of PsA. WNT ligands actively regulate osteoclastogenesis. We investigated how WNT ligands activate osteoclasts amid the TNF-α milieu in PsA. We first profiled the expression of WNT ligands in CD14+ monocyte-derived osteoclasts (MDOC) from five PsA patients and five healthy controls (HC) and then validated the candidate WNT ligands in 32 PsA patients and 16 HC. Through RNA interference against WNT ligands in MDOC, we determined the mechanisms by which TNF-α exerts its effects on osteclastogenesis or chemotaxis. WNT5A was selectively upregulated by TNF-α in MDOC from PsA patients. The number of CD68+WNT5A+ osteoclasts increased in PsA joints. CXCL1, CXCL16, and MCP-1 was selectively increased in supernatants of MDOC from PsA patients. RNA interference against WNT5A abolished the increased MCP-1 from MDOC and THP-1-cell-derived osteoclasts. The increased migration of osteoclast precursors (OCP) induced by supernatant from PsA MDOC was abolished by the MCP-1 neutralizing antibody. WNT5A and MCP-1 expressions were decreased in MDOC from PsA patients treated by biologics against TNF-α but not IL-17. We conclude that TNF-α recruits OCP by increased MCP-1 production but does not directly activate osteoclastogenesis in PsA.


2018 ◽  
Vol 3 (2) ◽  
pp. 54-58
Author(s):  
Eric J. Yang ◽  
Sahil Sekhon ◽  
Kristen M. Beck ◽  
Isabelle M. Sanchez ◽  
Tina Bhutani ◽  
...  

Treatments for psoriasis and psoriatic arthritis have progressed at a rapid rate over the past 20 years, but treating patients with recalcitrant disease still remains a difficult task. Current therapies for these diseases involve topical agents, phototherapy, and systemic immunosuppression. However, the role of the nervous system in psoriasis and psoriatic arthritis remains largely unexplored. Recent animal studies and clinical trials have demonstrated that vagus nerve stimulation can decrease inflammatory processes in rheumatoid arthritis and inflammatory bowel disease. In this article, we outline the existing knowledge of the nervous system’s role in chronic inflammatory disease and discuss how these findings could be utilized in the future for treatment of psoriasis and psoriatic arthritis.


2021 ◽  
pp. annrheumdis-2020-218744
Author(s):  
Irina Gessl ◽  
Mihaela Popescu ◽  
Victoria Schimpl ◽  
Gabriela Supp ◽  
Thomas Deimel ◽  
...  

ObjectivesTo determine whether clinical tenderness can be considered a sign of inflammatory joint activity in patients with rheumatoid arthritis (RA), osteoarthritis (OA) or psoriatic arthritis (PsA) and to assess other possible factors associated with tenderness.MethodsPatients diagnosed with RA, PsA and OA underwent clinical and ultrasound examination of wrists and finger joints. Radiographs of the hands were scored for erosions, joint space narrowing (JSN), osteophytes and malalignment. A binary damage score (positive if ≥1 erosion, JSN and/or presence of malalignment) was calculated. Differences in grey scale signs of synovitis and power Doppler (PD) between tender non-swollen (TNS) versus non-tender non-swollen (NTNS) joints were calculated. Disease duration was assessed,<2 years was regarded as early and >5 years as long-standing arthritis.ResultsIn total, 34 patients (9 early and 14 long-standing) from patients with RA, 31 patients (7 early and 15 long-standing) with PsA and 30 with OA were included. We found equal frequencies of PD signal between TNS and NTNS joints in RA (p=0.18), PsA (p=0.59) or OA (p=0.96). However, PD had a significant association with tenderness in early arthritis both in RA (p=0.02) and in PsA (p=0.02). The radiographic damage score showed significant association with tenderness in RA (p<0.01), PsA (p<0.01) and OA (p=0.04).ConclusionTenderness might not always be a sign of active inflammation in RA, PsA and OA. While tenderness in early arthritis may be more related to inflammation, established disease is better explained by joint damage and malalignment.


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