scholarly journals Expression and function of miR‑155 in rat synovial fibroblast model of rheumatoid arthritis

Author(s):  
Hewei Li ◽  
Ping Liu ◽  
Yanlin Gong ◽  
Jiali Liu ◽  
Feng Ruan
2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 540.3-540
Author(s):  
A. Munir ◽  
C. Sheehy

Background:Corneal melt is a rare inflammatory disease of the peripheral cornea; it may lead to perforation of the globe and visual failure. Corneal melt can be a manifestation of systemic vasculitis in patients with RA and other conditions, such as cancer. Without early and aggressive treatment it may be associated with a poor visual outcome and a high mortality. It has been reported in patients with stable RA.Objectives:A case report in a patient with long standing but well controlled Rheumatoid Arthritis (RA) and metastatic disease.Methods:A 75 year old male with a background of sero positive Rheumatoid Arthritis for more than 10 years presented to the Eye Casualty with a two week history of a painful left red eye. His other medical history was significant for Stage IIB poorly differentiated cancer of the left lower lobe. Left lower lobectomy with a patch of diaphragm resected. Intratumoural lymphovascular invasion noted. He completed Adjuvant Carboplatin/Vinorelbine chemotherapy September, 2017. He had DVT proximal left leg 22ndof September, 2017. Follow up CT in 2018 demonstrated a right renal upper pole lesion for which he was awaiting biopsy with?metastatic lung disease vs primary renal carcinoma. His RA was well controlled on Methotrexate 10mg weekly. He had been treated by the ophthalmology team for left marginal Keratitis for the prior 2 months with steroid eye drops without significant improvement. On presentation to ED, he described sharp eye pain, waking him from the sleep, associated with watery discharge and photophobia. Examination showed corneal melt in left eye involving 25% of inferior portion of the cornea and spastic entropion with injecting eye lashes. He had no active joints and there were no other signs of vasculitis. CRP was 4.1. He had a negative ANA and ANCA; viral swabs were negative. He was admitted under the medical team. Intravenous Methyl Prednisolone was started. The patient felt better after 5 days of Methyl Prednisolone. Left temporary tarsorrhaphy was done by Ophthalmology. Cyclophosphamide was initiated after discussion with Oncologist pending the result of the renal biopsy. Patient was discharged after 5 days of admission in the hospitalResults:The renal biopsy was positive for metastatic Squamous cell carcinoma of lung. Cyclophosphamide was withdrawn and he was started on Carboplatin/Gemcitabine. The corneal melt improved with complete resolution of his visual symptoms.Conclusion:In this case, although the history of RA was felt by the ophthalmology team to be the most likely association with the corneal melt, we would argue the oncological diagnoses were likely the driving force behind the presentation.References:[1]Sule A, Balakrishnan C, Gaitonde S, Mittal G, Pathan E, Gokhale NS, et al. Rheumatoid corneal melt. Rheumatology (Oxford)2002;41:705–6.[2]S. Yano, K. Kondo, M. Yamaguchi et al., “Distribution and function of EGFR in human tissue and the effect of EGFR tyrosine kinase inhibition,” Anticancer Research, vol. 23, no. 5, pp. 3639–3650, 2003.Disclosure of Interests:None declared


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 491.2-491
Author(s):  
M. Tada ◽  
Y. Yamada ◽  
K. Mandai ◽  
N. Hidaka

Background:We previously reported that the prevalence of sarcopenia was 28% in patients with rheumatoid arthritis (RA) in a cohort study 1. RA patients have a high risk of falls and fractures 2. However, the predictors of falls and fractures in RA patients are not known.Objectives:Whether evaluation of muscle mass and function at baseline could predict falls and fractures during four-year follow-up was investigated.Methods:The four-year follow-up data from a prospective, observational study (CHIKARA study: Correlation researcH of sarcopenIa, sKeletal muscle and disease Activity in Rheumatoid Arthritis) were used. Muscle mass was measured by a body impedance analyzer, and leg muscle mass was calculated. The leg muscle score (max: 100, min: 0) reflected the ratio of leg muscle mass to overall weight. Grip strength as an indicator of muscle function was evaluated using a digital, hand-held, isokinetic dynamometer. The correlations between muscle mass or function and falls or fractures were analyzed by survival rates and Cox hazard ratios. Leg muscle mass and grip strength were investigated by receiver operating characteristic (ROC) curve analysis for correlations with falls or fractures.Results:A total of 100 RA patients (female: 78%, mean age: 66.1 years) were enrolled; 35 patients had falls, and 19 patients had fractures during the four-year follow-up. The leg muscle score, grip strength, age, and fractures at baseline were significantly correlated with falls. The cut-off values of the leg muscle score and grip strength were calculated to be 84.5 points (sensitivity: 0.79, specificity: 0.43) and 15.9 kg (sensitivity: 0.56, specificity: 0.70), respectively, by ROC curve analysis. The patients were divided into four groups by their leg muscle scores and grip strength; the numbers of falls and fractures are shown in Table 1 for each group. The fall-free survival rate was significantly lower in the group with low leg muscle score and low grip strength (35.3%) than in the other groups (P=0.002) (Figure 1). The hazard ratio for the both low group was significantly increased, 3.6-fold (95%CI: 1.1-11.5), compared to that in the both high group.Table 1.Numbers of falls and fractures by category of leg muscle score and grip strengthLG + GS+(n=34)LG - GS+(n=12)LG + GS-(n=37)LG - GS-(n=17)P value*Falls, N6515110.010Fractures, N34660.072LG+: leg muscle score >84.5 points, GS+: grip strength >15.9kg, LG-: leg muscle score ≤84.5 points, GS+: grip strength ≤15.9kg*: compared in four groups by Kruskal-Walls test.Figure 1.Fall-free survival rate in the four groupsConclusion:RA patients with both low leg muscle score and low grip strength at baseline were at high risk for falls during the four-year follow-up period. Evaluation of muscle mass and function can predict falls in RA patients.References:[1]Tada, M., Yamada, Y., Mandai, K. & Hidaka, N. Matrix metalloprotease 3 is associated with sarcopenia in rheumatoid arthritis - results from the CHIKARA study. Int J Rheum Dis21, 1962-1969, doi:10.1111/1756-185X.13335 (2018).[2]van Staa, T. P., Geusens, P., Bijlsma, J. W., Leufkens, H. G. & Cooper, C. Clinical assessment of the long-term risk of fracture in patients with rheumatoid arthritis. Arthritis Rheum54, 3104-3112, doi:10.1002/art.22117 (2006).Disclosure of Interests:None declared


2015 ◽  
Vol 67 (8) ◽  
pp. 1075-1082 ◽  
Author(s):  
Ryosuke Yoshioka ◽  
Yasuhiro Kita ◽  
Asako Nagahira ◽  
Atsushi Manno ◽  
Naoyuki Makita ◽  
...  

1991 ◽  
Vol 34 (6) ◽  
pp. 679-686 ◽  
Author(s):  
Joseph Holoshitz ◽  
Jon Kosek ◽  
Richard Sibley ◽  
Daniel A. Brown ◽  
Samuel Strober

Author(s):  
Daniil Shevyrev ◽  
Valeriy Tereshchenko ◽  
Alexey Sizikov ◽  
Vladimir Kozlov

Homeostatic proliferation (HP) is a physiological process to reconstitute the T-cell pool after lymphopenia with IL-7 and IL-15 being the key cytokines regulating the process. However, there is no evidence whether these cytokines influence the function of regulatory T cells (Tregs). Since lymphopenia often accompanies autoimmune diseases, we decided to study the proliferation rate and function of Tregs stimulated by IL-7 and IL-15 in patients with rheumatoid arthritis (RA) compared to healthy donors (HD). The study used peripheral blood from 14 RA patients and 18 HD. Proliferation of purified CD3CD4CD25CD127 cells was assessed by flow cytometry using CFSE. Tregs were stimulated by anti-CD3, IL-7, IL-15, IL-7, or IL-15 combined with anti-CD3, and by IL-2+anti-CD3, and their functional activity was evaluated in each case by CD4 and CD8 cells proliferation inhibition. The suppressive activity of peripheral Tregs did not differ between RA and HD; however, it significantly decreased when IL-7 or IL-15 were applied together with strong TCR stimulation with anti-CD3 antibodies. Herewith Treg proliferation caused by IL-7 and IL-15 was lower in RA than in HD. The revealed decrease in Treg suppressive activity can lead to the proliferation of potentially self-reactive T-cell clones, which can receive relatively strong TCR signals. This may be another explanation of why lymphopenia is associated with the development of autoimmune diseases. The revealed decrease of Treg proliferation under IL-7 and IL-15 may lead to a delay in Treg pool reconstitution in patients with rheumatoid arthritis.


2019 ◽  
Author(s):  
Shutong Li ◽  
Hongxing Wang ◽  
Hui Wu ◽  
Guoqing Zhang ◽  
Xiaotian Chang

Abstract Background Regulatory T (Treg) cells have anti-inflammatory and anti-autoimmune functions. The proportion and functions of Treg cells are perturbed in rheumatoid arthritis (RA) patients. Methods Human Treg cells were induced to amplify in vitro and cocultured with RA synovial fibroblast cells (RASFs). The proliferation and apoptosis of RASFs were determined by the cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. Human Treg cells were also injected to collagen-induced arthritis (CIA) rats via the tail vein. Changes in lymphocyte subtypes and cytokines in the peripheral blood and spleen were observed by flow cytometry. Results After coculture with the Treg cells, the proliferation of RA synovial fibroblast cells decreased (p<0.01), and the rate of apoptosis increased (p=0.037). The human Treg cells were injected into the tail veins of collagen-induced arthritis (CIA) rats. The severity of the CIA was reduced (p<0.01) following the injection, the percentages of rat endogenous Treg cells in the peripheral blood and spleen increased significantly (p=0.007 and p<0.01, respectively), and the proportion of B cells decreased (p=0.031). The levels of interleukin IL-5 and IL-6 and the Th1/Th2 ratio in the peripheral blood were significantly decreased (p=0.013, 0.009 and 0.012, respectively). The number of NK cells and the levels of IL-4, IL-13, TNF-α, IFN-γ and GM-CSF in the peripheral blood and spleen did not change significantly. Conclusion These results suggest that exogenous Treg cells play a therapeutic role in RA and CIA. Treg cell treatment could serve as a therapy for RA.


Author(s):  
Andrew Filer ◽  
Maria Juarez ◽  
Christopher Buckley

In order to understand and explore the function and roles of fibroblasts, it is necessary to understand their lineage relationships to other mesenchymal cells. Fibroblasts are ubiquitous non-epithelial, non-endothelial, and non-haematopoietic adherent cells that have the capacity to produce and remodel extracellular matrix. In addition to their well-known ’landscaping’ function which determines the unique structure and function of different organs, they play an important role in wound healing, immune tolerance, and disease. In cancer, epithelial-stromal interactions have been implicated in disease initiation and progression. In rheumatoid arthritis, synovial fibroblasts at diseased sites become persistently activated and behave abnormally, orchestrating joint inflammation and contributing to joint destruction. Recent evidence suggests that the activated phenotype of fibroblasts in pathology may result from epigenetic programming, which is becoming a major focus for development of new therapeutics.


Sign in / Sign up

Export Citation Format

Share Document