Dynamics and correlations in multiplex immune profiling reveal persistent immune inflammation in male drug users after withdrawal

Re, Guo-Fen; Jia, Jie; Xu, Yu; Zhang, Zunyue; Xie, Zhenrong; Kong, Deshenyue; Lu, Dan; Li, Yue; Peng, Qingyan; Yu, Juehua; Kuang, Yi‐Qun; Wang, Kunhua

doi:10.1016/j.intimp.2022.108696

Cited by 12 publications

(15 citation statements)

References 77 publications

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“…Participants that reported recreational drug use, including marijuana, cocaine, and amphetamines had marginally higher log 2 Ab compared to non-users after PV, but not BV1 or BV2. Previous work has shown that recreational drug use is immunomodulatory, increasing the susceptibility to infectious diseases and microbes while impairing antibody production following vaccination (30–33). Our findings support the opposite, though this warrants further investigation given the small sample size of drug users in our cohort.…”

Section: Discussionmentioning

confidence: 99%

Determinants of health as predictors for differential antibody responses following SARS-CoV-2 primary and booster vaccination in an at-risk, longitudinal cohort

Tribin,

Williams,

Testamarck

et al. 2023

Preprint

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Post vaccine immunity following COVID-19 mRNA vaccination may be driven by extrinsic, or controllable and intrinsic, or inherent health factors. Thus, we investigated the effects of extrinsic and intrinsic on the peak antibody response following COVID-19 primary vaccination and on the trajectory of peak antibody magnitude and durability over time. Participants in a longitudinal cohort attended visits every 3 months for up to 2 years following enrollment. At baseline, participants provided information on their demographics, recreational behaviors, and comorbid health conditions which guided our model selection process. Blood samples were collected for serum processing and spike antibody testing at each visit. Cross-sectional and longitudinal models (linear-mixed effects models) were generated to assess the relationship between selected intrinsic and extrinsic health factors on peak antibody following vaccination and to determine the influence of these predictors on antibody over time. Following cross-sectional analysis, we observed higher peak antibody titers after primary vaccination in females, those who reported recreational drug use, younger age, and prior COVID-19 history. Following booster vaccination, females and Hispanics had higher peak titers after the 3rdand 4thdoses, respectively. Longitudinal models demonstrated that Moderna mRNA-1273 recipients, females, and those previously vaccinated had increased peak titers over time. Moreover, drug users and half-dose Moderna mRNA-1273 recipients had higher peak antibody titers over time following the first booster, while no predictive factors significantly affected post-second booster antibody responses. Overall, both intrinsic and extrinsic health factors play a significant role in shaping humoral immunogenicity after initial vaccination and the first booster. The absence of predictive factors for second booster immunogenicity suggests a more robust and consistent immune response after the second booster vaccine administration.

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Section: Discussionmentioning

confidence: 99%

Determinants of health as predictors for differential antibody responses following SARS-CoV-2 primary and booster vaccination in an at-risk, longitudinal cohort

Tribin,

Williams,

Testamarck

et al. 2023

Preprint

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“…However, even after 12 months of abstinence, immune dysfunction still exists and may persist for longer times in heroin and methamphetamine users. 21 Therefore, in this report, we opted for a simultaneous intranasal and intravenous administration of the hMSC-derived secretome.…”

Section: Discussionmentioning

confidence: 99%

“…Recent evidence suggests that the deregulated tone in glutamatergic activity is increased by glial immune activation. Opioids, including morphine, have been associated with an increase in both systemic and brain oxidative stress and inflammation 19–22 . Morphine can promote glial activation, and the subsequent increase in oxidative stress and inflammatory markers, by the direct activation of μ‐opioid receptors 23,24 .…”

Section: Introductionmentioning

confidence: 99%

Amelioration of morphine withdrawal syndrome by systemic and intranasal administration of mesenchymal stem cell‐derived secretome in preclinical models of morphine dependence

Quezada,

Ponce,

Berríos‐Cárcamo

et al. 2023

CNS Neurosci Ther

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BackgroundMorphine is an opiate commonly used in the treatment of moderate to severe pain. However, prolonged administration can lead to physical dependence and strong withdrawal symptoms upon cessation of morphine use. These symptoms can include anxiety, irritability, increased heart rate, and muscle cramps, which strongly promote morphine use relapse. The morphine‐induced increases in neuroinflammation, brain oxidative stress, and alteration of glutamate levels in the hippocampus and nucleus accumbens have been associated with morphine dependence and a higher severity of withdrawal symptoms. Due to its rich content in potent anti‐inflammatory and antioxidant factors, secretome derived from human mesenchymal stem cells (hMSCs) is proposed as a preclinical therapeutic tool for the treatment of this complex neurological condition associated with neuroinflammation and brain oxidative stress.MethodsTwo animal models of morphine dependence were used to evaluate the therapeutic efficacy of hMSC‐derived secretome in reducing morphine withdrawal signs. In the first model, rats were implanted subcutaneously with mini‐pumps which released morphine at a concentration of 10 mg/kg/day for seven days. Three days after pump implantation, animals were treated with a simultaneous intravenous and intranasal administration of hMSC‐derived secretome or vehicle, and withdrawal signs were precipitated on day seven by i.p. naloxone administration. In this model, brain alterations associated with withdrawal were also analyzed before withdrawal precipitation. In the second animal model, rats voluntarily consuming morphine for three weeks were intravenously and intranasally treated with hMSC‐derived secretome or vehicle, and withdrawal signs were induced by morphine deprivation.ResultsIn both animal models secretome administration induced a significant reduction of withdrawal signs, as shown by a reduction in a combined withdrawal score. Secretome administration also promoted a reduction in morphine‐induced neuroinflammation in the hippocampus and nucleus accumbens, while no changes were observed in extracellular glutamate levels in the nucleus accumbens.ConclusionData presented from two animal models of morphine dependence suggest that administration of secretome derived from hMSCs reduces the development of opioid withdrawal signs, which correlates with a reduction in neuroinflammation in the hippocampus and nucleus accumbens.

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“…In this subset analysis, cytokine PC1 scores remained a positive predictor of HUD, adjusting for the other variables (not shown). More broadly, we employed a simplified two-step approach for dimensionality reduction: first focusing on 29 targets that differed significantly between iHUD and HC, and secondly with PCA based on a subset of 19 targets that are members of canonical cytokine families 17,23 . Other methods to elucidate the optimal components of a "cytokine PC score" for use in iHUD can also be evaluated in larger studies.…”

Section: Other Inflammatory Targets (Not Part Of Canonical Cytokine F...mentioning

confidence: 99%

Serum cytokine and inflammatory markers in individuals with heroin use disorder: potential biomarkers for diagnosis and disease severity

Butelman,

Huang,

Cathomas

et al. 2024

Preprint

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Opioid use disorders cause major morbidity and mortality, and there is a pressing need for novel mechanistic targets and biomarkers for diagnosis and prognosis. Exposure to mu-opioid receptor (MOR) agonists causes changes in cytokine and inflammatory protein networks in peripheral blood, and also in brain glia and neurons. Individuals with heroin use disorder (iHUD) show dysregulated levels of several cytokines in blood. However, there is limited data on a comprehensive panel of such markers in iHUD versus healthy controls (HC), especially as a multi-target biomarker. We used a validated proximity extension assay for relative quantification of 92 cytokines and inflammatory proteins in serum of iHUD on medication assisted therapy (MAT; n=21), versus HC (n=24). Twenty-nine targets showed significant group differences (primarily iHUD>HC), surviving multiple comparison correction (p=0.05). This included 19 members of canonical cytokine families, including specific chemokines, interleukins, growth factors, and tumor necrosis factor (TNF)-related proteins. For dimensionality reduction, data from these 19 cytokines were entered into a principal component (PC) analysis, and PC1 scores were iHUD>HC (p<0.0001). A receiver-operating characteristic (ROC) curve analysis yielded an AUROC=91.7% (p<0.0001). This PC1 score remained a positive predictor of being in the HUD group in a multivariable logistic regression, which included demographic/clinical variables. Overall, this study shows a panel of cytokines that differ significantly between iHUD and HC, and provides a multi-target cytokine biomarker score for potential diagnostic purposes, and examination of disease severity.

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Dynamics and correlations in multiplex immune profiling reveal persistent immune inflammation in male drug users after withdrawal

Cited by 12 publications

References 77 publications

Determinants of health as predictors for differential antibody responses following SARS-CoV-2 primary and booster vaccination in an at-risk, longitudinal cohort

Determinants of health as predictors for differential antibody responses following SARS-CoV-2 primary and booster vaccination in an at-risk, longitudinal cohort

Amelioration of morphine withdrawal syndrome by systemic and intranasal administration of mesenchymal stem cell‐derived secretome in preclinical models of morphine dependence

Serum cytokine and inflammatory markers in individuals with heroin use disorder: potential biomarkers for diagnosis and disease severity

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