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1.
Rev Med Interne ; 41(8): 545-551, 2020 Aug.
Article in French | MEDLINE | ID: mdl-32624260

ABSTRACT

The holistic approach of the human immune system is based on the study of its components collectively driving a functional response to an immunogenic stimulus. To appreciate a specific immune dysfunction, a condition is mimicked ex vivo and the immune response induced is assessed. The application field of such assays are broad and expanding, from the diagnosis of primary and secondary immunodeficiencies, immunotherapy for cancer to the management of patients at-risk for infections and vaccination. These assays are immune monitoring tools that may contribute to a personalised and precision medicine. The purpose of this review is to describe immune functional assays available in the setting of non-HIV acquired immune deficiency. First, we will address the use of theses assays in the diagnosis of opportunistic infections such as viral reactivation. Secondly, we will report the usefulness of these assays to assess vaccine efficacy and to manage immunosuppressive therapies.


Subject(s)
Drug Monitoring/methods , Immunocompromised Host , Immunosuppressive Agents/therapeutic use , Opportunistic Infections/diagnosis , Humans , Immunoassay/methods , Immunoassay/standards , Immunocompromised Host/drug effects , Opportunistic Infections/chemically induced , Opportunistic Infections/metabolism , Precision Medicine/methods , Predictive Value of Tests , Risk Factors , Virus Activation/drug effects , Virus Activation/physiology , Virus Diseases/chemically induced , Virus Diseases/diagnosis
2.
In Silico Biol ; 14(1-2): 101-121, 2020.
Article in English | MEDLINE | ID: mdl-32597796

ABSTRACT

A dynamical model of the pathophysiological behaviors of IL18 and IL10 cytokines with their receptors is tested against data for the case of early sepsis. The proposed approach considers the surroundings (organs and bone marrow) and the different subsystems (cells and cyctokines). The interactions between blood cells, cytokines and the surroundings are described via mass balances. Cytokines are adsorbed onto associated receptors at the cell surface. The adsorption is described by the Langmuir model and gives rise to the production of more cytokines and associated receptors inside the cell. The quantities of pro and anti-inflammatory cytokines present in the body are combined to give global information via an inflammation level function which describes the patient's state. Data for parameter estimation comes from the Sepsis 48 H database. Comparisons between patient data and simulations are presented and are in good agreement. For the IL18/IL10 cytokine pair, 5 key parameters have been found. They are linked to pro-inflammatory IL18 cytokine and show that the early sepsis is driven by components of inflammatory character.


Subject(s)
Adjuvants, Immunologic/therapeutic use , Cytokines/immunology , Sepsis/drug therapy , Adjuvants, Immunologic/pharmacology , Anti-Inflammatory Agents/therapeutic use , Cytokines/metabolism , Cytokines/therapeutic use , Female , Humans , Inflammation , Interleukin-10/metabolism , Interleukin-18/metabolism , Male , Models, Immunological , Sepsis/immunology , Sepsis/metabolism , Shock, Septic/drug therapy , Shock, Septic/immunology , Shock, Septic/metabolism , Treatment Outcome
3.
Clin Exp Immunol ; 176(3): 401-9, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24460818

ABSTRACT

The mechanisms sustaining the absence of complete immune recovery in HIV-infected patients upon long-term effective highly active anti-retroviral therapy (HAART) remain elusive. Immune activation, regulatory T cells (T(regs)) or very low-level viraemia (VLLV) have been alternatively suspected, but rarely investigated simultaneously. We performed a cross-sectional study in HIV-infected aviraemic subjects (mean duration of HAART: 12 years) to concomitantly assess parameters associated independently with inadequate immunological response. Patients were classified as complete immunological responders (cIR, n = 48) and inadequate immunological responders (iIR, n = 39), depending on the CD4(+) T cell count (> or < 500/mm(3)). Clinical and virological data (including very low-level viraemia) were collected. In parallel, immunophenotyping of CD4(+) lymphocytes, including T(reg) subsets, and CD8(+) T cells was performed. Percentages of activated CD4(+) T cells, T(regs), effector T(regs) and terminal effector T(regs) were found to be significantly elevated in iIR. Neither the percentage of activated CD8(+) T cells nor VLLV were found to be associated with iIR. In the multivariate analysis, nadir of CD4(+) T cell count and percentage of T(regs) were the only two parameters associated independently with iIR [odds ratio (OR) = 2·339, P = 0·001, and OR = 0·803, P = 0·041]. We present here the largest study investigating simultaneously the immune response to long-term HAART, activation of CD4(+) and CD8(+) T cells, T(reg) percentages and very low-level viraemia. Causative interactions between T(regs) and CD4(+) T cells should now be explored prospectively in a large patients cohort.


Subject(s)
Antiretroviral Therapy, Highly Active , HIV Infections/drug therapy , HIV Infections/immunology , Lymphocyte Activation/immunology , T-Lymphocytes, Regulatory/immunology , Adult , Aged , CD4 Lymphocyte Count , Cross-Sectional Studies , Female , HIV Infections/virology , HLA-DR Antigens/immunology , Humans , Immunity, Cellular , Immunophenotyping , Male , Middle Aged , T-Lymphocytes, Regulatory/metabolism , Treatment Outcome , Viral Load , Viremia
4.
Pathol Biol (Paris) ; 59(6): 329-33, 2011 Dec.
Article in French | MEDLINE | ID: mdl-21981928

ABSTRACT

Septic syndromes (systemic inflammatory response associated with infection) remain a major although largely under-recognized health care problem and represent the first cause of mortality in intensive care units. Regarding immune response, it is now agreed that sepsis induces an anti-inflammatory process, acting as a negative feedback. This inhibitory mechanism becomes deleterious as nearly all immune functions are rapidly compromised. The magnitude and persistence over time of this immunosuppression is correlated with nosocomial infections and mortality. Decreased HLA-DR expression on monocytes/increased percentage of regulatory T cells are biomarkers identifying patients at risk who could benefit from immunotherapy. This review attempts to integrate these new facts into an up-to-date account of sepsis pathophysiology.


Subject(s)
Cross Infection/epidemiology , Cross Infection/immunology , Immune Tolerance/physiology , Intensive Care Units , Sepsis/mortality , Sepsis/therapy , Biomarkers/analysis , Cross Infection/diagnosis , Cross Infection/therapy , Humans , Intensive Care Units/standards , Models, Biological , Precision Medicine/methods , Prognosis , Sepsis/diagnosis , Sepsis/immunology
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