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Epidemiological evidence shows that adverse experiences, particularly, but not exclusively in childhood, are predictors of poor long-term health outcomes and certain social domains. In the field of rheumatic diseases, traumatic events, not only in childhood, have been associated with hospitalization, chronic pain, inflammation, worse outcomes, severity of the disease, and mortality. Some mechanisms proposed to explain the association between the experience of adversity and the development of chronic diseases include an impact on the physiology of immune system cells, gene expression due to DNA modification, and cellular senescence.
With this background, the investigators wonder if, for patients with rheumatoid arthritis, the presence of adversity understood as a history of violence in childhood and abuse due to suffering from rheumatoid arthritis is associated with markers of cellular senescence and with the severity of illness.
To answer this question, the investigators proposed conducting a study on outpatients diagnosed with rheumatoid arthritis treated at the INCMNSZ.
Patients who agree to participate will be asked to answer some questionnaires to report their perception of child abuse and abuse derived from suffering from rheumatoid arthritis, disease activity, disability, quality of life, anxiety, stress, depression, and resilience.
Additionally, a peripheral blood sample will be taken to evaluate cellular senescence through CD27, CD28, and CD57 expression, the relative expression of the p16INK4a gene in CD3+ lymphocytes, HLA-DR, CD25, and CD69, and telomere length. Finally, the expression of the severity of the disease will be determined.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients with rheumatoid arthritis | Patients with rheumatoid arthritis outpatients from the National Institute of Medical Sciences |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rheumatic diseases Mistreatment Scale (RDMS) | Other | In 2012, Giraldo-Rodríguez developed and validated the Geriatric Mistreatment Scale (GAS); translation, cultural adaptation, and validation were performed prior to its application. |
| Measure | Description | Time Frame |
|---|---|---|
| Adversity and senescence in patients with rheumatoid arthritis | To evaluate whether the presence of adversity (history of abuse in childhood and/or abuse associated with RD) is associated with markers of senescence in patients with rheumatoid arthritis. | At inclusion (baseline moment) (cross-sectional study)] |
| Measure | Description | Time Frame |
|---|---|---|
| Eexpression of the p16INK4a gene in CD3+ | Compare the relative expression of the p16INK4a gene in CD3+ lymphocytes between rheumatoid arthritis patients with and without adversity. | At inclusion (baseline moment) (cross-sectional study)] |
| Telomere length |
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Inclusion Criteria:
Exclusion Criteria:
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All the patients with rheumatoid arthritis outpatients from the National Institute of Medical Sciences
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Virginia MD Pascual-Ramos, MD | Contact | 525555734111 | 533 | virtichu@gmail.com |
| Irazu MD Contreras-Yáñez, MD | Contact | 525555734111 | 533 | virtichu@gmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Virginia MD Pascual-Ramos, MD | IInstituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34048701 | Result | Baumer Y, Powell-Wiley TM. Interdisciplinary approaches are fundamental to decode the biology of adversity. Cell. 2021 May 27;184(11):2797-2801. doi: 10.1016/j.cell.2021.04.010. |
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A 10 ml peripheral blood sample will be taken by venipuncture with the Vacutainer® system in tubes with EDTA anticoagulant. DNA will be extracted using the commercial Wizard® system (Promega TM cat: A1620) based on salt precipitation. The extracted DNA will be quantified in a Nanodrop spectrophotometer, diluted, and preserved at -20°C until use. The Institute's Cellular Immunology and Genetics laboratories will analyze the DNA.
|
| Routine assessment of patient index data 3 (RAPID-3) | Other | RAPID- 3 measures: function, pain, and patient global status estimate. Each of the three individual measures is scored 0 to 10, for a total of 30 |
|
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| Health Assessment Questionnaire (HAQ) | Other | The HAQ is based on five patient-centered dimensions: disability, pain, medication effects, costs of care, and mortality. |
|
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| WHOQOL-BREF | Other | WHOQOL-BREF is a 26-item instrument consisting of four domains: physical health, psychological health, social relationships, and environmental health; it also contains QOL and general health items |
|
| Depression, Anxiety and Stress Scale (DASS-21) | Other | DASS-21 is a set of three self-report scales designed to measure the emotional states of depression, anxiety, and stress. Each of the three DASS-21 scales contains seven items, divided into subscales with similar content. |
|
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| Brief Resilient Coping Scale | Other | The Brief Resilient Coping Scale is a 4-item measure designed to capture tendencies to cope with stress in a highly adaptive manner. |
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| Expression of CDKN2A /p16INK4a | Genetic | CDKN2A/p16INK4a expression will be measured using the Taqman qPCR assay (TaqMan Universal Master Mix II, with UNG, Applied Biosystems, Foster City, USA) according to the manufacturer's specifications. |
|
| Immunophenotype of leukocyte subpopulations | Other | CD4+ and CD8+ subpopulations will be analyzed. Blood samples will be analyzed by 8-color flow cytometry (Becton Dickinson Canto II cytometer) using fluorescently labeled antibodies from Biolegend Inc. (San Diego, USA). |
|
| Telomere length | Genetic | The rLTL will be estimated by quantitative monochromatic multiplex PCR (MM-qPCR). Integrated DNA Technologies, Inc. (IDT, Coralville, IA, USA) will synthesize the primers used for telomere measurements. |
|
| Cellular senescence | Other | Expression of co-stimulatory molecules and surface receptors CD27- and CD28- |
|
Compare telomere length between RA patients with and without adversity. |
| At inclusion (baseline moment) (cross-sectional study)] |
| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| D012216 | Rheumatic Diseases |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C020182 | ametantrone |
| D019941 | Cyclin-Dependent Kinase Inhibitor p16 |
| D016922 | Cellular Senescence |
| ID | Term |
|---|---|
| D050756 | Cyclin-Dependent Kinase Inhibitor Proteins |
| D047908 | Intracellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D018797 | Cell Cycle Proteins |
| D011506 | Proteins |
| D025521 | Tumor Suppressor Proteins |
| D009363 | Neoplasm Proteins |
| D002468 | Cell Physiological Phenomena |
| D000375 | Aging |
| D048788 | Growth and Development |
| D010829 | Physiological Phenomena |
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