Perceived Discrimination, Geography, and Demographic Effects on Immune Cell Function and Regulation
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 480
- 试验地点
- 4
- 主要终点
- Gene expression levels
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Outcomes Assessor)
盲法说明
The participant and the outcomes assessor will be blinded to the conditions to reduce bias. Participants will not be informed about the specific conditions (race-based exclusion or non-race-based exclusion) they are experiencing during Cyberball game and will be instructed not to discuss their experiences with the investigator or the outcomes assessor. All participant's questionnaire responses, blood, and saliva samples are labeled with anonymized codes (computer-generated ID numbers) to prevent identification of the condition order and Cyberball randomizes sequences automatically. The outcomes assessor, who will analyze the blood and saliva samples for immune cell function and genomic and epigenetic markers and the questionnaire, will be unaware of the participants' assigned conditions. Data analysis will be performed on de-identified datasets and randomization managed by a separate team member not involved in data collection or analysis.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Gene expression levels
时间窗: PMBCs purified from whole blood collected collected 30 minutes after the first and 30 minutes after the second Cyberball sequence
RNA expression counts and distribution will be measured in PBMCs purified from participant whole blood collected participants after completing the first and second Cyberball sequences (collection tines separated by up 2 hours)
Frequency of Perceived Discrimination Experiences
时间窗: Survey response collected before the first Cyberball Sequence within 30 minutes of arriving at the lab) and score calculated during data analysis
Before the game, participants will be asked to complete the "Everyday Discrimination Scale" designed to measure their perceptions of discrimination encountered in their everyday lives. This instrument prompts respondents to rate the frequency of discriminatory events in their daily lives, such as "being treated with less courtesy than others." Everyday Discrimination Scale Participants provide their responses on a scale that ranges from "0" for "never" to "5" for "almost every day." The summed responses provide a measure of how frequently they experienced discrimination. The summed score can range from 0 to 50; the higher the score, the more frequently participants perceived that they experienced discrimination. Additionally, participants specify whether these experiences are due to various factors, including race and gender.
Type, Timing and Frequency of Lifetime Discrimination Experiences
时间窗: Survey response collected within 30 minutes after completing the first Cyberball Sequence and score calculated during data analysis]
The "Experiences of Discrimination Scale" measures the type, timing, and frequency of discrimination. Participants answer "yes" or "no" to 9 types of unfair treatment, such as, "Have you ever been unfairly fired?" The sum of "yes" responses ranges from 0 to 9, with a score above 6 indicating many unfair treatments. Participants also specify if the unfair treatment was due to race, skin color, or other characteristics. The sum of responses related to ancestry, race, ethnicity, or skin color indicates the frequency of racial discrimination. Additionally, participants report the last time they experienced unfair treatment due to race or ethnicity, with responses from 1 ("past week") to 4 ("more than a year"). Lower scores indicate more recent occurrences.
Distribution and Quantity of Immune Cells in Whole blood
时间窗: 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.
To determine the quantity of each type of peripheral blood mononuclear cells (PBMCs) available after the different Cyberball sequences, the PBMCs will be sorted and quantified from whole blood collected 30 minutes after the first and 30 minutes after the second Cyberball sequence. A Sony SH800 cell sorter is used to perform Fluorescence-Activated Cell Sorting (FACS) with appropriate antibodies to identify T cells (CD3+), B cells (CD19+), NK cells (CD56+), and monocytes (CD14+CD16-, CD14+CD16+) and counts provided of viable cells with the cell counter.
Recent Discrimination and Perceived Ethnic Discrimination Score
时间窗: Survey responses collected within 30 minutes after completing the Second Cyberball Sequence and score calculated during data analysis]
The sum of response scores for the Recent Discrimination (a) and Ethnic Discrimination (b) subscale items of the "General Ethnic Discrimination Scale"provides the frequency of recent discrimination experience and includes a manipulation check for the validity of the recent Cyberball condition Recent Discrimination is calculated as the sum of responses to all (a) items ranging from a choice of 1 for "never" to 6 for "almost all the time. A summed minimum score of 18 corresponds to no lifetime discrimination, and a summed maximum score of 108 corresponds to the most frequent experience of perceived lifetime discrimination. Lifetime Discrimination is calculated as the sum of all (b) item responses ranging from a choice of 1 for "never" to 6 for "almost all the time. A summed minimum score of 18 corresponds to no lifetime discrimination, and a summed maximum score of 108 corresponds to the most frequent experience of perceived lifetime discrimination.
Recent and Lifetime Discrimination Stress Score
时间窗: Survey responses collected within 30 minutes after completing the Second Cyberball Sequence and score calculated during data analysis
The Cumulative response score from the Stress from Discrimination (c) items on the General Ethnic Discrimination Scale measures a person's perception of the stress of recent and lifetime unfair treatment due to a participant's racial/ethnic identity. Participants are asked to respond to the statement "How stressful was this for you?" for each discrimination experience. Response choices range from 1 for "not at all stressful" to 6 for "extremely stressful." Discrimination Stress is calculated as the sum of all (c) items on the General Ethnic Discrimination (GED) scale, where a summed score of 17 indicates little to no stress, and 102 indicates the highest amount of stress experienced due to recent and lifetime discrimination experiences.
Relationship between salivary and serum immune responses
时间窗: 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.
Multiplex enzyme-linked immunosorbent assays (ELISA) will allow assessment of the pg/mL concentration of inflammatory cytokines in saliva and serum. These data will be used to calculate correlation coefficients that depict the magnitude and direction of the relationship between saliva and serum inflammatory cytokine concentration. The cytokines to be measured are Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α, and c-Reactive Protein (CRP).
Stimulated PBMC Cytokine Release
时间窗: 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
Cellular Cytokine release from (PBMCs) purified from the participant's whole blood is assessed in the presence or absence of stimulation with lipopolysaccharide (LPS) toxin. The LPS incubation time will vary in length, and ELISA will measure pg/ml concentration of IL-6, TNF-α, IL-1β, CRP
次要结局
- Degree of Morbidity(Survey responses are collected within 30 minutes after completing the second Cyberball sequence and the sum of response scores calculated during data analysis)
- Resilience(Survey responses are collected within 30 minutes after completing the second Cyberball sequence and the average response score calculated during data analysis)
- Average Community Risk Protective Factors(Survey responses are collected within 30 minutes after completing the first Cyberball sequence and score calculated during data analysis)
- Methylation Score(Methylsequencing of PMBCs purified from whole blood collected collected 30 minutes after the first and 30 minutes after the second Cyberball sequence)
- Average Community Protective Factors(Survey responses are collected within 30 minutes after completing the first Cyberball sequence and score calculated during data analysis)
- Magnitude of Race/Ethnic Residential Segregation (Dissimilarity Index)(Questionnaire responses to the zip code items are collected within first 30 minutes in the lab and Index calculated during data analysis)
- Frequency of recent stress(Survey responses are collected within 30 minutes after completing the first Cyberball sequence and Perceived Stress score calculated during data analysis)
研究者
Ingrid Tulloch
Associate Professor
Morgan State University