Adversity and Its Association With the Development and Expression of Rheumatic Diseases (RD)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: RhA - Rheumatoid Arthritis
• Intervention / Treatment: Other: WHOQOL-BREF; Genetic: Expression of CDKN2A /p16INK4a; Other: Immunophenotype of leukocyte subpopulations; Other: Cellular senescence; Other: Rheumatic diseases Mistreatment Scale (RDMS); Other: Routine assessment of patient index data 3 (RAPID-3); Other: Health Assessment Questionnaire (HAQ); Other: Depression, Anxiety and Stress Scale (DASS-21); Other: Brief Resilient Coping Scale; Genetic: Telomere length

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 110

Contacts and Locations

• Study Contact: Name: Virginia MD Pascual-Ramos, MD; Phone Number: 533 525555734111; Email: virtichu@gmail.com
• Study Contact Backup: Name: Irazu MD Contreras-Yáñez, MD; Phone Number: 533 525555734111; Email: virtichu@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All the patients with rheumatoid arthritis outpatients from the National Institute of Medical Sciences

Description

Inclusion Criteria:

• Patients with a rheumatoid arthritis diagnosis, according to their primary rheumatologist who agrees to participate

Exclusion Criteria:

• Patients with a not confirmed rheumatoid arthritis diagnosis

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Patients with rheumatoid arthritis; Patients with rheumatoid arthritis outpatients from the National Institute of Medical Sciences

Other: WHOQOL-BREF; 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; Genetic: Expression of CDKN2A /p16INK4a; 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.; Other: Immunophenotype of leukocyte subpopulations; 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).; Other: Cellular senescence; Expression of co-stimulatory molecules and surface receptors CD27- and CD28-; Other: Rheumatic diseases Mistreatment Scale (RDMS); In 2012, Giraldo-Rodríguez developed and validated the Geriatric Mistreatment Scale (GAS); translation, cultural adaptation, and validation were performed prior to its application.; Other Names: RD-MS; Other: Routine assessment of patient index data 3 (RAPID-3); 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; Other Names: RAPID-3; Other: Health Assessment Questionnaire (HAQ); The HAQ is based on five patient-centered dimensions: disability, pain, medication effects, costs of care, and mortality.; Other Names: HAQ; Other: Depression, Anxiety and Stress Scale (DASS-21); 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.; Other Names: DASS-21; Other: Brief Resilient Coping Scale; The Brief Resilient Coping Scale is a 4-item measure designed to capture tendencies to cope with stress in a highly adaptive manner.; Other Names: BRCS; Genetic: Telomere length; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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)]

Secondary Outcome Measures

Outcome Measure	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	Compare telomere length between RA patients with and without adversity.	At inclusion (baseline moment) (cross-sectional study)]

Collaborators and Investigators

• Sponsor: National Institute of Medical Sciences and Nutrition, Salvador Zubiran
• Investigators: Principal Investigator: Virginia MD Pascual-Ramos, MD, IInstituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: April 23, 2024
• First Submitted That Met QC Criteria: April 23, 2024
• First Posted (Actual): April 26, 2024

Study Record Updates

• Last Update Posted (Estimated): May 3, 2024
• Last Update Submitted That Met QC Criteria: May 1, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Rheumatic diseases; Adversity
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Rheumatic Diseases; Collagen Diseases
• Other Study ID Numbers: IRE-4906

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No