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Personalized inherent randomness of the immune system is manifested by an individualized response to immune triggers and immunomodulatory therapies: a novel platform for designing personalized immunotherapies

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Abstract

The considerable variability of responses amongst subjects to disease triggers and immunotherapies is a major obstacle to designing better immune-based therapies. Therefore, development of patient-tailored precision medicine that improves the efficacy of immunomodulatory drugs is necessary. The individualized response to disease triggers and immunomodulatory therapies was studied using the concanavalin A (ConA) immune-mediated hepatitis model and the oral administration of anti CD3 or β-glucosylceramide (GC). Mice were treated with anti-CD3 antibodies or GC followed by an injection of ConA. The effects of these treatments on liver damage and the immune profile were then analyzed. An individualized response to ConA and orally administered immunomodulatory agents was observed in eight consecutive experiments. While alleviation of the immune-mediated liver injury, as measured by serum levels of liver enzymes, was seen, and high intra-group and inter-experimental variabilities were detected. A similar individualized response was observed for the effect on serum levels of IFN-γ, TNF-α, and IL-10 and on CD4+CD25+, CD8+CD25+, and CD3+NK1.1+ lymphocytes. A personalized form of inherent randomness in an isolated system was documented, which may underlie the variability in responses to immune triggers and immunomodulatory therapies. The data support the use of personalized randomness-based platforms for improving the response to chronic therapies.

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Abbreviations

GC:

β-glucosylceramide

ConA:

Concanavalin A

NKT:

Natural killer T

AST:

Aspartate aminotransferase

ALT:

Alanine aminotransferase

IFN-γ:

Interferon gamma

TNF-α:

Tumor necrosis factor alpha

IL10:

Interleukin 10

PDL1:

Programmed death-ligand 1

PD:

Programmed death-1

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  1. Department of Medicine, Hadassah-Hebrew University Medical Center, P.O.B 12000, IL-91120, Jerusalem, Israel

    Madi El-Haj, Dimitri Kanovitch & Yaron Ilan

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  1. Madi El-Haj
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Correspondence to Yaron Ilan.

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Animal experiments were carried out according to the guidelines of the Hebrew University-Hadassah Institutional Committee for the Care and Use of Laboratory Animals and with the committee’s approval.

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YI is a founder of Oberon Sciences and consultant for Teva, ENZO, Protalix, Betalin Therapeutics, Immuron, SciM, Natural Shield, Tiziana Pharma, Plantylight, and Exalenz Bioscience.

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El-Haj, M., Kanovitch, D. & Ilan, Y. Personalized inherent randomness of the immune system is manifested by an individualized response to immune triggers and immunomodulatory therapies: a novel platform for designing personalized immunotherapies. Immunol Res 67, 337–347 (2019). https://doi.org/10.1007/s12026-019-09101-y

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