scholarly journals Canonical (CD74/CD44) and Non-Canonical (CXCR2, 4 and 7) MIF Receptors Are Differentially Expressed in Rheumatoid Arthritis Patients Evaluated by DAS28-ESR

2021 ◽  
Vol 11 (1) ◽  
pp. 120
Author(s):  
Gabriela Athziri Sánchez-Zuno ◽  
Richard Bucala ◽  
Jorge Hernández-Bello ◽  
Ilce Valeria Román-Fernández ◽  
Mariel García-Chagollán ◽  
...  

Macrophage migration inhibitory factor (MIF) significantly contributes to rheumatoid arthritis (RA) pathogenesis. We aimed to evaluate the canonical (CD74/CD44) and non-canonical MIF receptors (CXCR2,4 and 7) expression and sCD74 to establish their association with RA clinical activity according to DAS28-ESR. Methodology: 101 RA patients with different clinical activities (remission (n = 27), low (n = 16), moderate (n = 35) and high (n = 23)) and 9 control subjects (CS) were included. Expression was evaluated by flow cytometry and levels of soluble CD74 (sCD74) by ELISA. Data analysis was performed with FlowJov10.0, STATAv12.0, and GraphPad Prism v7.0. Results: According to disease activity, CXCR7 expression (percentage of expression and mean fluorescence intensity (MFI)) was higher in granulocytes from patients in remission, while the expression of CXCR4 was higher in patients with high disease activity (p < 0.05). The expression of CD74 was higher in B cells (p < 0.05) and monocytes (p < 0.01) from patients in remission. Regarding sCD74 levels these were higher in patients with high disease activity when compared to those in remission (p <0.05). Conclusions: The results support the need for further study of the role of sCD74 as a soluble MIF decoy receptor, sequestering it to negatively regulate MIF signaling though its membrane receptors. The expression patterns of CXCR4 and CXCR7 show that the latter is a scavenger-type receptor that prevents endocytosis and even degradation of CXCR4 under inflammatory conditions.

2009 ◽  
Vol 69 (3) ◽  
pp. 618-623 ◽  
Author(s):  
Lode Melis ◽  
Bernard Vandooren ◽  
Elli Kruithof ◽  
Peggy Jacques ◽  
Martine De Vos ◽  
...  

ObjectivesTh17 cells are an effector T-cell population that plays a role in chronic inflammatory conditions and is dependent on IL-23 for their survival and expansion. More recently, a genetic association was discovered between polymorphisms in the gene coding for the IL-23 receptor and spondyloarthritis. This study aimed to evaluate the role of Th17-associated cytokines in spondyloarthritis pathogenesis by measuring their levels in the joints and circulation as well as correlating them with disease activity parameters.MethodsPaired synovial fluid (SF), serum and synovial biopsies were obtained from 30 non-PsA (psoriatic arthritis) spondyloarthritis, 22 PsA and 22 rheumatoid arthritis (RA) patients. IL-17, IL-23 and CCL20 were measured by ELISA in the SF and serum of patients and correlated with systemic and local parameters of disease activity.ResultsConcentrations of CCL20, a major Th17-attracting chemokine, tended to be higher in the joints of RA than in spondyloarthritis patients. Interestingly, levels of CCL20 were markedly higher in SF as opposed to serum. In addition, there was a remarkable association between the expression of the Th17 cytokine system and the presence of intimal lining layer hyperplasia in RA. Also in the serum, there was a tendency for higher IL-23 levels in RA, which correlated strongly with disease activity parameters.ConclusionsTh17-related cytokines are expressed in joints of spondyloarthritis as well as RA patients. IL-23 levels, however, correlate with disease activity parameters in RA only. These results point towards a differential regulation of the Th17 cytokine system in spondyloarthritis compared with RA.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Lang Yi ◽  
Mingju Hao ◽  
Tian Lu ◽  
Guigao Lin ◽  
Lida Chen ◽  
...  

Theκ/λhybrid antibodies in normal human serum were reported recently, but their clinical relevance has not yet been explored. Rheumatoid arthritis (RA) is one of the major joint diseases, and the early diagnosis and treatment of RA remain a challenge. Here, we developed a double-sandwich enzyme-linked immunosorbent assay system to quantify relative serumκ/λhybrid antibody levels in RA patients, osteoarthritis (OA) patients, and healthy controls (HC) in order to assess their potential use as a serological biomarker of early disease and clinical activity and to preliminarily investigate their immunomodulatory roles in RA. Surprisingly, we found thatκ/λhybrid antibody was markedly increased in both early and established RA. Serumκ/λhybrid antibody levels were significantly correlated with clinical indexes and inflammatory markers in RA. Further analysis showed a positive correlation betweenκ/λhybrid antibody levels and the 28-joint disease activity score (DAS28). In conclusion, serumκ/λhybrid antibodies in RA were identified for the first time. High levels ofκ/λhybrid antibody may be a useful tool in distinguishing early RA from OA and HC. We suggestκ/λhybrid antibody as a marker for disease activity. The increasedκ/λhybrid antibodies were associated with inflammatory conditions in RA.


Author(s):  
Muhannad Mohammed Ali AL-Salami ◽  
Abeer Thaher Naji AL-Hasnawi ◽  
Mohammed Abd AbdulHussein Abusabe

2018 ◽  
Vol 86 (September) ◽  
pp. 3341-3348
Author(s):  
DALIA B. EL-BOHOTY, M.Sc.; DOAA S. AL-ASHKAR, M.D. ◽  
MAALY M. MABROUK, M.D.; HALA M. NAGY, M.D.

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 583-583
Author(s):  
C. Garufi ◽  
F. Ceccarelli ◽  
F. R. Spinelli ◽  
S. Mancuso ◽  
C. Pirone ◽  
...  

Background:In the management of chronic arthritis, such as Rheumatoid Arthritis (RA), Ultrasound (US) assessment can provide relevant information about the joint inflammatory status in the diagnostic phase and even more in the monitoring of disease activity and structural damage1,2.Objectives:In this longitudinal study, we aimed to assesse the role of US in predicting the efficacy of JAK-inhibitors (JAKi) in RA patients.Methods:We enrolled RA patients starting baricitinib or tofacitinib. All patients were evaluated at baseline and after 4, 12, 24, 48 weeks. Disease activity was calculated by DAS28CRP. US examination in 22 joints (I–V MCPs and PIPs, wrists) aimed at evaluating inflammatory features (synovial effusion and hypertrophy, power Doppler-PD), through a semi-quantitative scale (0-3). The total US (0-198) and PD (0-66) scores were calculated. We scanned bilateral flexor (I–V fingers of hands) and extensor compartments (1-6) tendons: tenosynovitis was scored as absent/present (0/1), resulting in a total score (0-22).Results:We studied 102 patients (M/F 15/87; median age 59.2 years, IQR 17.75; median disease duration 144 months, IQR 126), 61 treated with baricitinib and 41 with tofacitinib. At baseline, the median total US score was 18 (IQR 19) and the median PD score 2 (4). We observed a significant reduction in both total and PD US scores at all time-points (p<0.0001) (Figure 1). At baseline, 75.4% of patients showed tenosynovitis involving at least one tendon, with a median score of 2 (IQR 3.5) significantly decreasing after 24 weeks (p=0.02). Multivariate analysis, adjusted for baseline DAS28CRP and other concomitant treatments (including glucocorticoids and methotrexate treatment), confirmed the independent association between baseline US (PD and tenosynovitis) scores and the reduction of disease activity at follow-up evaluations.Conclusion:The present study confirmed the early efficacy of JAKi in RA patients by using US evaluation. Furthermore, power doppler and tenosynovitis scores could play a predictive role in response to treatment.References:[1]MUELLER RB, HASLER C, POPP F, et al. Effectiveness, Tolerability, and Safety of Tofacitinib in Rheumatoid Arthritis: A Retrospective Analysis of Real-World Data from the St. Gallen and Aarau Cohorts. J Clin Med. 2019;8(10):1548.[2]COLEBATCH AN, EDWARDS CJ, ØSTERGAARD M, et al. EULAR recommendations for the use of imaging of the joints in the clinical management of rheumatoid arthritis. Ann Rheum Dis. 2013;72(6):804-14.Figure 1.Ultrasound inflammatory score (a) and Ultrasound Power Doppler (PD) score (b) at baseline and follow-up.Table 1.Baseline characteristics of 414 RA patients.WEEKS04122448US inflammatory score18 (19)11 (15.5)9.5 (11.7)7.5 (8)6 (11)US PD score2 (4)0 (2)0 (1)0 (1)0 (0.7)Disclosure of Interests:Cristina Garufi: None declared, Fulvia Ceccarelli: None declared, Francesca Romana Spinelli Speakers bureau: Abbvie, Eli Lilly, Consultant of: Gilead/Galapagos, Eli Lilly, Grant/research support from: Pfizer, Silvia Mancuso: None declared, Carmelo Pirone: None declared, Fabrizio Conti Speakers bureau: Abbvie, Eli Lilly, Sanofi, Pfizer, Consultant of: Gilead/Galapagos


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 378-379
Author(s):  
B. Fautrel ◽  
R. Caporali ◽  
E. Holdsworth ◽  
B. Donaghy ◽  
M. Khalid ◽  
...  

Background:The principles of treat to target (T2T) include defining an appropriate treatment target, assessed at pre-defined intervals, with a commitment to changing therapeutic approach if the target is not met (1). T2T is recommended as a key strategy for the treatment of rheumatoid arthritis (RA).Objectives:To explore attitudes towards T2T, its implementation and stated treatment goals among physicians and their patients with RA.Methods:The Adelphi RA Disease Specific Programme™ was a large, quantitative, point-in-time survey conducted amongst rheumatologists (n=296) and their consulting patients with RA (n=3042) in Europe (France, Germany, Italy, Spain, UK) between Q4 2019–Q3 2020. Physicians were recruited via publicly available lists, completing an online survey and medical record extraction for their next 10–12 consecutive patients. The same patients were invited to voluntarily complete a self-report questionnaire (n=1098, 36% response), collecting data on attitudes towards T2T and treatment goals.Results:Physicians reported that 76% of patients were in remission (DAS28: <2.6) or had low disease activity (DAS28: 2.6 – 3.2), and 24% had moderate-high disease activity (DAS28: >3.2). Patient mean age was 53.0 years (SD 14.0), mean time since diagnosis was 7.2 years (SD 7.2). The proportion of patients currently receiving an advanced therapy (AT; defined as biologic or targeted synthetic DMARD) was 68%, of whom 70% were on a first line AT. No difference was observed between disease activity groups.In the physician survey, 86% of physicians stated they followed T2T principals in at least some of their RA patients, and would utilize a T2T approach in RA patients with moderate-high disease activity (61%), the most uncontrolled patients (37%) and those who do not respond well to initial therapy (34%). In this sample of real-world RA patients, 66% were reported by physicians to be on a T2T plan at the time of data collection. The most common physician-reported targets were remission (DAS28: <2.6) (75%), improvement of quality of life (QoL) (41%) and reduction of pain (31%), with 85% of physicians perceiving these treatment goals were fully or partially met. The most stated reasons for not implementing T2T was physician preference not to adjust current treatment (34%), patient preference not to adjust current treatment (23%), and there are no achievable goals for this patient (16%).Overall, 29% of patients reported they were involved in setting their T2T goals, while 34% stated their T2T goals were set by their physicians only, and 29% perceived no T2T goal had been set (n=620). The most common overall T2T goals from the patient perspective were remission (61%), controlling symptoms (41%), and reducing impact on QoL (34%). Of those patients who acknowledged a T2T goal had been set (n=407), 77% reported their T2T goal was fully or partially achieved.Of 719 patients who had moderate-high disease activity, 57% were on a T2T plan, with 46% of physicians perceiving these treatment goals were fully or partially met. The most common physician-stated reason for not implementing T2T was a lack of achievable targets (29%).Conclusion:Rheumatologists in this study reported a strong belief in T2T. The most common physician-set T2T goals were remission, improvement of QoL and reduction of pain, corresponding with T2T goals as reported by patients. However, a third of patients in this cohort were not aware of a defined T2T objective in their management, which may be a result of a perceived lack of achievable goals by physicians. It may be desirable to promote more patient involvement in defining achievable targets amongst those with moderate-high disease activity who despite best efforts may not reach a clinical state of remission. Further research is needed to identify and understand goals important to RA patients.References:[1]van Vollenhoven R. Treat-to-target in rheumatoid arthritis - are we there yet? Nat Rev Rheumatol. 2019;15(3):180-6.Acknowledgements:This study was funded by Galapagos NV, Belgium.Medical writing support was provided by Gary Sidgwick, PhD (Adelphi Real World, Bollington, UK) and editorial support was provided by Debbie Sherwood, BSc, CMPP (Aspire Scientific, Bollington, UK), both funded by Galapagos NV.Disclosure of Interests:Bruno Fautrel Consultant of: AbbVie, Amgen, Biogen, BMS, Celgene, Celltrion, Fresenius Kabi, Gilead, Janssen, Lilly, Medac, MSD, Mylan, NORDIC Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi-Genzyme, SOBI, UCB, Grant/research support from: AbbVie, Lilly, MSD, Pfizer, Roberto Caporali Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Celltrion, Galapagos, Gilead, Lilly, Pfizer, Roche, UCB, Sanofi, Fresenius Kabi, Samsung Bioepis, MSD, Consultant of: Galapagos, Gilead, Lilly, Janssen, MSD, Elizabeth Holdsworth Employee of: Adelphi Real World, Bethany Donaghy Employee of: Adelphi Real World, Mona Khalid Shareholder of: Galapagos, Employee of: Galapagos, Mark Moore Shareholder of: Gilead Sciences, Speakers bureau: Gilead Sciences (only as employee), Paid instructor for: Gilead Sciences (only as employee), Consultant of: Gilead Sciences (only as employee), Grant/research support from: Gilead Sciences (only as employee), Employee of: Gilead Sciences, and previously Sanofi and AstraZeneca, Katrien Van Beneden Shareholder of: Galapagos, Employee of: Galapagos, Yves Piette Consultant of: AbbVie, Amgen, Galapagos, Grünenthal and Sandoz, Grant/research support from: Amgen, Mylan and UCB, Susana Romero-Yuste Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Grunenthal, Kern Pharma, Lilly, Roche, Sandoz, Sanofi, UCB, Janssen, Consultant of: AbbVie, Biogen, Fresenius, Galapagos, Gebro, Janssen, Lilly, Grant/research support from: Bristol Myers Squibb, MSD, Novartis, Pfizer, Jasper Broen Shareholder of: Pharming Group, Consultant of: Galapagos, Gilead, Novartis, Peter C. Taylor Consultant of: AbbVie, Biogen, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, Pfizer, Roche, Sanofi, Nordic Pharma, Fresenius, UCB, Grant/research support from: Celgene, Galapagos, Gilead, Lilly


2015 ◽  
Vol 42 (7) ◽  
pp. 1090-1098 ◽  
Author(s):  
Leslie R. Harrold ◽  
George W. Reed ◽  
Ashwini Shewade ◽  
Robert Magner ◽  
Katherine C. Saunders ◽  
...  

Objective.To characterize the real-world effectiveness of rituximab (RTX) in patients with rheumatoid arthritis.Methods.Clinical effectiveness at 12 months was assessed in patients who were prescribed RTX based on the Clinical Disease Activity Index (CDAI). Change in CDAI was calculated (CDAI at 12 mos minus at initiation). Achievement of remission or low disease activity (LDA; CDAI ≤ 10) among those with moderate/high disease activity at the time of RTX initiation was compared based on prior anti-tumor necrosis factor agent (anti-TNF) use (1 vs ≥ 2) using logistic regression models.Results.Patients (n = 265) were followed for 12 months with a mean change in CDAI of −8.1 (95% CI −9.8 – −6.4). Of the 218 patients with moderate/high disease activity at baseline, patients with 1 prior anti-TNF (baseline CDAI 25.0) demonstrated a mean change in CDAI of −10.1 (95% CI −13.2 – −7.0); patients with ≥ 2 prior anti-TNF (baseline CDAI 30.0) demonstrated a mean change of −10.5 (95% CI −12.9 – −8.0). The unadjusted OR for achieving LDA/remission in patients with moderate/high disease activity at baseline exposed to ≥ 2 versus 1 prior anti-TNF was 0.40 (95% CI 0.22–0.73), which was robust to 4 different adjusted models (OR range 0.38–0.44).Conclusion.A good clinical response was observed in all patients; however, patients previously treated with 1 anti-TNF, who had lower baseline CDAI and a greater opportunity for clinical improvement compared with patients previously treated with ≥ 2 anti-TNF, were more likely to achieve LDA/remission.


2010 ◽  
Vol 67 (4) ◽  
pp. 286-290 ◽  
Author(s):  
Aleksandra Tomic-Lucic ◽  
Suzana Pantovic ◽  
Gvozden Rosic ◽  
Zdravko Obradovic ◽  
Mirko Rosic

Background/Aim. Many arguments prove the pathophysiologic role of histamine in the process of remodeling and joint destruction in rheumatoid arthritis. The aim of our study was to find out if there was a relation between histamine concentration in synovial fluid and blood with clinical expression of disease activity. Methods. Histamine concentration in synovial fluid and blood was determinated in 19 patients with rheumatoid arthritis. Histamine concentration measurement was based on the Shore's fluorometric method. Histamine index (HI) was evaluated as a ratio between histamine concentration in synovial fluid and blood. Disease activity score, DAS 28 (3), with three variables (erythrocyte sedimentation rate, the number of swelled joints and the number of tender joints) was also evaluated. Results. Our results showed that there was no significant difference in concentration of histamine in synovial fluid and blood related to disease activity. However, there was a significant difference in the histamine index which was increased proportionally with disease activity. Conclusion. Our study indicates that histamine index could be useful in estimation of rheumatoid arthritis activity.


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