Molecular mechanisms underlying rheumatoid arthritis and cancer development and treatment

2020 ◽  
Author(s):  
Susan Morand ◽  
Hannah Staats ◽  
Justin Fortune Creeden ◽  
Azwar Iqbal ◽  
Bashar Kahaleh ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Molecular Mechanisms ◽  
Checkpoint Inhibitors ◽  
Immune Therapy ◽  
Joint Damage ◽  
Cancer Development ◽  
Disease Modifying Antirheumatic Drugs ◽  
Growth And Survival ◽  
Increased Risk ◽  
Development Risk

Given recent advances in cancer immune therapy, specifically use of checkpoint inhibitors, understanding the link between autoimmunity and cancer is essential. Rheumatoid arthritis (RA) affects about 1% of the population, and early diagnosis is key to prevent joint damage. Management consists of disease-modifying antirheumatic drugs that alter normal immunologic pathways, which could affect malignancy growth and survival. Prolonged immune dysregulation and the resulting inflammatory response associated with development of RA may also lead to increased cancer development risk. RA has long been associated with increased risk of non-Hodgkin's lymphoma [ 1 ] and further evidence supports relationship to lung cancer [ 2 ]. This review will address the mechanisms behind cancer development and progression in RA patients, biomarkers and assess cancer risk and early detection.

scholarly journals From Oncogenic Signaling Pathways to Single-Cell Sequencing of Immune Cells: Changing the Landscape of Cancer Immunotherapy

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2278
Author(s):  
Afshin Derakhshani ◽  
Zeinab Rostami ◽  
Hossein Safarpour ◽  
Mahdi Abdoli Shadbad ◽  
Niloufar Sadat Nourbakhsh ◽  
...  
Keyword(s):  
Single Cell ◽  
Signaling Pathways ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cancer Development ◽  
Immune Checkpoints ◽  
Single Cell Sequencing ◽  
Increased Risk

Over the past decade, there have been remarkable advances in understanding the signaling pathways involved in cancer development. It is well-established that cancer is caused by the dysregulation of cellular pathways involved in proliferation, cell cycle, apoptosis, cell metabolism, migration, cell polarity, and differentiation. Besides, growing evidence indicates that extracellular matrix signaling, cell surface proteoglycans, and angiogenesis can contribute to cancer development. Given the genetic instability and vast intra-tumoral heterogeneity revealed by the single-cell sequencing of tumoral cells, the current approaches cannot eliminate the mutating cancer cells. Besides, the polyclonal expansion of tumor-infiltrated lymphocytes in response to tumoral neoantigens cannot elicit anti-tumoral immune responses due to the immunosuppressive tumor microenvironment. Nevertheless, the data from the single-cell sequencing of immune cells can provide valuable insights regarding the expression of inhibitory immune checkpoints/related signaling factors in immune cells, which can be used to select immune checkpoint inhibitors and adjust their dosage. Indeed, the integration of the data obtained from the single-cell sequencing of immune cells with immune checkpoint inhibitors can increase the response rate of immune checkpoint inhibitors, decrease the immune-related adverse events, and facilitate tumoral cell elimination. This study aims to review key pathways involved in tumor development and shed light on single-cell sequencing. It also intends to address the shortcomings of immune checkpoint inhibitors, i.e., their varied response rates among cancer patients and increased risk of autoimmunity development, via applying the data from the single-cell sequencing of immune cells.

scholarly journals Incidence of inpatient venous thromboembolism in treated patients with rheumatoid arthritis and the association with switching biologic or targeted synthetic disease-modifying antirheumatic drugs (DMARDs) in the real-world setting

RMD Open ◽  
2019 ◽  
Vol 5 (2) ◽  
pp. e001013 ◽  
Author(s):  
Huifang Liang ◽  
Raghava Danwada ◽  
Dianlin Guo ◽  
Jeffrey R Curtis ◽  
Ryan D Kilpatrick ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cox Regression ◽  
Incidence Rates ◽  
Disease Modifying Antirheumatic Drugs ◽  
Vein Thrombosis ◽  
Real World Setting ◽  
Increased Risk ◽  
Safety Studies ◽  
Unbiased Estimates ◽  
Deep Vein

ObjectivesTo assess incidence rates (IRs) of VTE in patients with rheumatoid arthritis (RA) on different DMARDs and DMARD switchers.MethodsAdults with RA on a DMARD between 2007 and 2017 were studied in a US claims database. Conventional synthetic DMARD (csDMARD) users, first biologic/targeted synthetic DMARD (b/tsDMARD) users and b/tsDMARD switchers (from a b/tsDMARD to another b/tsDMARD) were followed for inpatient VTE (pulmonary embolism (PE)/deep vein thrombosis (DVT)). Crude and adjusted IR and 95% CIs of VTE were estimated. HRs for VTE were estimated via Cox regression. VTE risk was also evaluated by number of switches between b/tsDMARDs and in patients without a VTE history.ResultsThe age and sex standardised IR (95% CI) of VTE (per 100 person-years) was 0.86 (0.70 to 1.03), 0.60 (0.52 to 0.68) and 0.58 (0.51 to 0.65) for b/tsDMARD switchers, first b/tsDMARD users and csDMARD users, respectively. After adjustment, b/tsDMARD switchers had an increased risk of VTE, compared with csDMARD users, HRadj (95% CI) being 1.36 (1.16 to 1.58), 1.36 (1.13 to 1.63) and 1.47 (1.18 to 1.83) for VTE, DVT and PE, respectively. Compared with first b/tsDMARD users, the HRadj (95% CI) for VTE was 1.35 (1.15 to 1.60) for first b/tsDMARD switchers and 1.48 (1.19 to 1.85) for second b/tsDMARD switchers.ConclusionsIn RA, b/tsDMARD switchers have a higher VTE risk compared with csDMARD users and first b/tsDMARD users. Switching b/tsDMARDs may be a proxy for higher disease severity or poorly controlled RA and an important confounder to consider in obtaining unbiased estimates of VTE risk in observational RA safety studies.

High Levels of Polypharmacy in Rheumatoid Arthritis—A Challenge Not Covered by Current Management Recommendations: Data From a Large Real-Life Study

2019 ◽  
pp. 089719001986915 ◽  
Author(s):  
Ana Paula M. Gomides ◽  
Cleandro P. Albuquerque ◽  
Ana B.V. Santos ◽  
Rodrigo B. C. Amorim ◽  
Manoel B. Bértolo ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Activity Index ◽  
Real Life ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Cross Sectional ◽  
Rheumatic Arthritis ◽  
Increased Risk ◽  
Disease Modifying

Background: Rheumatoid arthritis (RA) is associated with high frequency of comorbidities and increased risk of polypharmacy. Although there is a great potential for complications, there is a gap in literature on polypharmacy in patients with rheumatic arthritis. Objective: To evaluate the prevalence and factors associated with polypharmacy in a population in a real-life setting. Methods: A cross-sectional multicenter study was conducted in Brazil. Patients underwent clinical evaluation and medical records analysis. Polypharmacy was considered as a dependent variable. To test independent variables, we used Poisson regression. Results: We evaluated 792 patients (89% female, median age 56.6 years). Median duration of disease was 12.7 years, 78.73% had a positive rheumatoid factor. The median of disease activity score-28 was 3.5 (disease with mild activity), median of the clinical disease activity index score was 9, and median of health assessment questionnaire-disability index was 0.875; 47% used corticosteroids, 9.1% used nonsteroidal anti-inflammatory drugs, 90.9% used synthetic disease-modifying antirheumatic drugs, 35.7% used biologic disease-modifying antirheumatic drugs (DMARDs). In total, 537 (67.9%) patients used 5 or more drugs. Polypharmacy showed a relationship with a number of comorbidities and use of specific drugs (corticosteroids, methotrexate, and biological DMARDs). Conclusion: We found a high prevalence of polypharmacy (67.9%) in RA. Solutions to management this problem should be stimulated.

scholarly journals A Case of Diverticular Perforation in a Young Patient with Rheumatoid Arthritis on Methotrexate

2015 ◽  
Vol 2015 ◽  
pp. 1-2 ◽  
Author(s):  
Ian Chang ◽  
Carla Guggenheim ◽  
Heather Laird-Fick
Keyword(s):  
Rheumatoid Arthritis ◽  
Dihydrofolate Reductase ◽  
Methylenetetrahydrofolate Reductase ◽  
Gastrointestinal Disease ◽  
Gastrointestinal Toxicity ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Increased Risk ◽  
Disease Modifying ◽  
Concomitant Exposure

Background. Disease-modifying antirheumatic drugs (DMARDs), such as methotrexate (MTX), are associated with gastrointestinal toxicity. MTX inhibits dihydrofolate reductase, but it is unclear if polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene predict toxicity.Case. We describe a 33-year-old male with polyarticular rheumatoid arthritis who developed sigmoid diverticular perforation while receiving methotrexate, folic acid, prednisone, and naproxen. He tested heterozygous for the C677T alleleMTHFRgene.Discussion. Rheumatoid arthritis and its treatments are associated with increased risk of gastrointestinal disease. In one study, perforation was highest among individuals with concomitant exposure to NSAIDs, nonbiologic DMARDs, and glucocorticoids. Multiple mutations of theMTHFRgene have been identified, but their association with MTX toxicity is unclear. This case adds to a growing body of literature that could help inform the treatment of others in the future.

scholarly journals Associations of Alcohol Use with Radiographic Disease Progression in African Americans with Recent-onset Rheumatoid Arthritis

2013 ◽  
Vol 40 (9) ◽  
pp. 1498-1504 ◽  
Author(s):  
Marshall L.R. Davis ◽  
Kaleb Michaud ◽  
Harlan Sayles ◽  
Doyt L. Conn ◽  
Larry W. Moreland ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
African Americans ◽  
Alcohol Consumption ◽  
Alcohol Use ◽  
Disease Progression ◽  
Joint Damage ◽  
Alcoholic Beverages ◽  
Recent Onset ◽  
Increased Risk ◽  
Radiographic Disease

Objective.To investigate the associations of alcohol consumption and radiographic disease progression in African Americans with recently diagnosed rheumatoid arthritis (RA).Methods.Patients with RA included in the study were participants in the Consortium for the Longitudinal Evaluation of African Americans with Early Rheumatoid Arthritis (CLEAR) registry. Patients were categorized based on self-reported alcohol consumption; those consuming < 15 beverages per month versus those with ≥ 15 per month. Association of radiographic disease progression over a 1-year to 3-year period of observation with alcohol consumption was evaluated using multivariate generalized estimating equations.Results.Of 166 patients included in the study, 39% reported that they had never consumed alcohol. Of the 61% who had consumed alcohol, 73% reported that they consumed on average < 15 alcoholic beverages per month and 27% reported consuming ≥ 15 per month. In multivariate analysis, consumption of ≥ 15 alcoholic beverages per month was associated with an increased risk of radiographic disease progression (p = 0.017). There was no evidence of a relationship in those consuming < 15 beverages per month (p = 0.802).Conclusion.There appears to be a dose-dependent relationship between alcohol use and radiographic disease progression in RA. Individuals who consume 15 or more alcoholic beverages per month may have faster rates of radiographic joint damage than those with lower levels of consumption.

scholarly journals Cost Effectiveness Analysis of Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis. A Systematic Review Literature

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Maurizio Benucci ◽  
Gianantonio Saviola ◽  
Mariangela Manfredi ◽  
Piercarlo Sarzi-Puttini ◽  
Fabiola Atzeni
Keyword(s):  
Rheumatoid Arthritis ◽  
Cost Effectiveness ◽  
Disease Activity ◽  
Disease Onset ◽  
Critical Evaluation ◽  
Joint Damage ◽  
Review Literature ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Disease Modifying

The cost effectiveness of treatments that have changed the “natural history” of a chronic progressive disease needs to be evaluated over the long term. Disease-modifying antirheumatic drugs (DMARDs) are the standard treatment of rheumatoid arthritis (RA) and should be started as early as possible. A number of studies have shown that they are effective in improving disease activity and function, and in joint damage. Our review was focused on revision and critical evaluation of the studies including the literature on cost effectiveness of DMARDs (cyclosporine A, sulphasalazine, leflunomide, and methotrexate). The European League Against Rheumatism (EULAR) recommendations showed that traditional DMARDs are cost effective at the time of disease onset. They are less expensive than biological DMARDs and can be useful in controlling disease activity in early RA.

scholarly journals C-C chemokine receptor type 5 links COVID-19, Rheumatoid arthritis, and Hydroxychloroquine: In silico analysis 

2020 ◽  
Author(s):  
MAHMOOD Yaseen HACHIM ◽  
Ibrahim Hachim ◽  
Kashif Naeem ◽  
Haifa Hannawi ◽  
Issa Al Salmi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
In Silico ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
In Silico Analysis ◽  
Cell Recruitment ◽  
Beneficial Effects ◽  
Increased Risk ◽  
Patient Groups ◽  
Chemotactic Factors

Abstract Patients with rheumatoid arthritis (RA) represent one of the fragile patient groups that might be susceptible to the critical form of the coronavirus disease -19 (COVID-19) . On the other side, RA patients have been found not to have an increased risk of COVID-19 infection. Moreover, some of the Disease-Modifying Anti-Rheumatic Drugs (DMARDS) commonly used to treat rheumatic diseases like Hydroxychloroquine (HCQ) were proposed as a potential therapy for COVID-19 with a lack of full understanding of their molecular mechanisms. This highlights the need for the discovery of common pathways that may link both diseases at the molecular side. In this research, we used the in silico approach to investigate the transcriptomic profile of RA synovium to identify shared molecular pathways with that of severe acute respiratory syndrome-corona virus-2 (SARS-COV-2) infected lung tissue. Our results showed upregulation of chemotactic factors, including CCL4, CCL8, and CCL11, that all shared CCR5 as their receptor, as a common derangement observed in both diseases; RA and COVID-19. Moreover, our results also highlighted a possible mechanism through which HCQ, which can be used as a monotherapy in mild RA or as one of the triple-DMARDs therapy (tDMARDs; methotrexate, sulphasalazine, and HCQ), might interfere with the COVID-19 infection. This might be achieved through the ability of HCQ to upregulate specific immune cell populations like activated natural killer (NK) cells, which were found to be significantly reduced in COVID-19 infection. In addition to its ability to block CCR5 rich immune cell recruitment that also was upregulated in the SARS-COV-2 infected lungs. This might explain some of the reports that showed beneficial effects.

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