Social Experiences and Demographic Factors in the Regulation of Immune Cells

Official title

Perceived Discrimination, Geography, and Demographic Effects on Immune Cell Function and Regulation

Overview

Immune-mediated inflammatory diseases are a health burden for approximately seven percent of the population of Western nations. Preliminary data suggest variations in ethnic identity and/or geography influence discrimination experiences and inflammatory response trends. This study investigates how geography, ethnicity, and laboratory manipulation of discrimination experiences affect immune cell function and genomic regulation. Flow cytometry and immune cell stimulation will test monocytes collected from peripheral blood for functional effects. Next-generation transcriptomics and epigenomics will assess genomic and epigenetic mechanisms. The hypothesis is that geography, self-identified race, and ethnicity, interacting with laboratory discrimination conditions during the virtual ballgame Cyberball™, significantly affect immune cell function through genomic and epigenetic mechanisms, with perceived discrimination as a moderating factor on the immune outcomes. The transdisciplinary nature of the proposed study aims to provide valuable insights into differential susceptibility to immune-mediated inflammatory diseases across diverse populations. Uncovering these insights will better inform population-relevant interventions for immune-mediated inflammatory diseases.

Detailed description

More than a third of the residents of the United States suffer from a chronic disease, with almost half involving dysregulated immune processes. Immune-mediated inflammatory diseases pose a public health burden in the United States. Preliminary data from previous work suggest that variations in ethnic identity and geography might influence discrimination experiences and inflammatory response trends. To investigate the functional implications of these findings, a multi-institutional study is proposed, examining how social experiences and demographic factors predict the regulation and activity of immune cells. Specifically, the hypothesis is that geography, self-identified race, and ethnicity, interacting with laboratory discrimination conditions, significantly affect immune cell function through genomic and epigenetic mechanisms, with perceived discrimination moderating the immune outcomes. Participants will provide saliva samples, complete psychosocial and demographic questionnaires, and play the virtual social exclusion game Cyberball™ in a randomly assigned block order. Acute discrimination experiences are manipulated by conditions during Cyberball. Virtual players, who appear to be of a different race from the participant, exclude them by not passing the participant the ball in the race-based exclusion condition. In the inclusion condition, the participant receives the ball regardless of participant and virtual player race. In the general social exclusion (not race-based), the players and participant races are similar to the inclusion condition, except that the participant does not receive the ball. The block of Cyberball and blood draws randomly assigned are either: 1) race-based social exclusion and inclusion first, a blood draw, then non-race-based social exclusion, inclusion, and blood draw, or 2) non-race-based social exclusion and inclusion, a blood draw and then the race-based social exclusion and inclusion and a blood draw. Baseline and post-first block inflammatory responses in saliva will be measured using enzyme-linked immunosorbent assays (ELISAs) to determine the concentration of cytokines like C-reactive protein, interleukin-6, and tumor necrosis factor-alpha. Flow cytometry and immune cell stimulation with toxin will test monocytes purified and sorted from the participant's blood for functional effects. Next-generation transcriptomics and epigenomics will assess differentially expressed RNA and methylation enrichment, emphasizing genes involved in inflammation signaling pathways. The data will be statistically analyzed using regression analysis and structural equation modeling to determine the relationship between discrimination, geography, immune cell function, and regulation while controlling for other socio-demographic factors. The findings could inform public health initiatives and interventions to reduce health disparities and improve outcomes for marginalized communities.

Interventions

• Behavioral Cyberball
  Cyberball™ is a virtual social exclusion game that simulates social interactions and acute discrimination experiences in a controlled laboratory setting. The game involves passing a virtual ball between players represented by images. In this study, only the participant is a real player, while the other "players" are pre-programmed virtual avatars controlled by the experimenter using Cyberball software. The ethnicity of these virtual players can be manipulated by changing the stock photos used to

Primary outcome measures

• Frequency of Perceived Discrimination Experiences [Time frame: Survey response collected before the first Cyberball Sequence within 30 minutes of arriving at the lab) and score calculated during data analysis]
• Type, Timing and Frequency of Lifetime Discrimination Experiences [Time frame: Survey response collected within 30 minutes after completing the first Cyberball Sequence and score calculated during data analysis]]
• Recent Discrimination and Perceived Ethnic Discrimination Score [Time frame: Survey responses collected within 30 minutes after completing the Second Cyberball Sequence and score calculated during data analysis]]
• Recent and Lifetime Discrimination Stress Score [Time frame: Survey responses collected within 30 minutes after completing the Second Cyberball Sequence and score calculated during data analysis]
• Relationship between salivary and serum immune responses [Time frame: Samples used in assay are saliva collected at baseline (30 mins before) and 40 minutes after the first Cyberball sequence, and serum is purified from whole blood collected 30 minutes after the first and second Cyberball sequence.]
• Distribution and Quantity of Immune Cells in Whole blood [Time frame: These data will be from whole blood samples collected 30 minutes after the first and 30 minutes after the second Cyberball sequence. The sequences are between 90 to 120 minutes apart separated by a washout period.]
• Stimulated PBMC Cytokine Release [Time frame: PMBCs purified from whole blood collected collected 30 minutes after the first and 30 minutes after the second Cyberball sequence are compared at 0, 2, 24 and 26 hours after incubation in LPS]
• Gene expression levels [Time frame: PMBCs purified from whole blood collected collected 30 minutes after the first and 30 minutes after the second Cyberball sequence]

Secondary outcome measures (7)

• Magnitude of Race/Ethnic Residential Segregation (Dissimilarity Index) [Time frame: Questionnaire responses to the zip code items are collected within first 30 minutes in the lab and Index calculated during data analysis]
• Average Community Risk Protective Factors [Time frame: Survey responses are collected within 30 minutes after completing the first Cyberball sequence and score calculated during data analysis]
• Average Community Protective Factors [Time frame: Survey responses are collected within 30 minutes after completing the first Cyberball sequence and score calculated during data analysis]
• Resilience [Time frame: Survey responses are collected within 30 minutes after completing the second Cyberball sequence and the average response score calculated during data analysis]
• Frequency of recent stress [Time frame: Survey responses are collected within 30 minutes after completing the first Cyberball sequence and Perceived Stress score calculated during data analysis]
• Degree of Morbidity [Time frame: Survey responses are collected within 30 minutes after completing the second Cyberball sequence and the sum of response scores calculated during data analysis]
• Methylation Score [Time frame: Methylsequencing of PMBCs purified from whole blood collected collected 30 minutes after the first and 30 minutes after the second Cyberball sequence]

Eligibility criteria

Inclusion criteria

• Non-Hispanic Black, Non-Hispanic White, or Hispanic
• At least 18 years of age
• Lives within 25 miles of, works, or attends Morgan State University, The University of Baltimore or Texas Christian University

Exclusion criteria

• Anyone not identifying as either non-Hispanic Black, non-Hispanic White, or Hispanic,
• Under 18 years old
• Does not live within 25 miles of, works, or attends Morgan State University, the University of Baltimore or Texas Christian University

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Crossover

Masking

Double blind

Primary purpose

Basic science

Study locations

United States · 2 centers

• Morgan State University — Baltimore
• Texas Christian University — Fort Worth

Identifiers

NCT: NCT06519487 · 2407001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗