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Altered Phenotype and Functionality of Circulating Immune Cells Characterize Adult Patients with Nonalcoholic Steatohepatitis

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Abstract

Nonalcoholic steatohepatitis (NASH) is a chronic inflammatory liver disease associated with insulin resistance and its metabolic consequences. Leukocyte mobilization, intrahepatic activation, and an exacerbated production of reactive oxygen species (ROS) and cytokines contribute to the development of NASH. Though alterations in peripheral blood (PB) T cell proportions and functionality remain unidentified, they might play a main role in NASH progression. We have compared the phenotype and Th1/Th2 commitment of peripheral immune cell reservoirs in adult patients and controls as well as the ability of neutrophils and monocytes to handle an ex vivo challenge. Also, we correlated those parameters with the main histological characteristics in NASH. Compared with controls, patients showed increased numbers of CD4+ cells and both CD4+ and CD8+ CD45RO subsets together with a higher frequency of IFN-γ-producing CD4+ and CD8+ T cells. We also found a decreased number of CD4+ and CD8+ CD45RA subsets. The distinctive production of IFN-γ highlights the significance of the observed skewed frequencies of PB T cells. Whereas ROS production by monocytes from NASH patients did not differ from controls, circulating neutrophils displayed a particularly higher phorbol myristate acetate-induced production of ROS. A negative correlation between oxidative burst and fibrosis grade was observed. This study reveals the presence of a characteristic profile of peripheral immune cells in NASH. We also discuss the probable influence of obesity on some of our present findings.

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Acknowledgments

We wish to thank the patients for their cooperation. We also thank Dr. A.E. Feldstein for proofreading our manuscript.

Source of Funding

This work was supported by the Buenos Aires University (UBACyT M010); CONICET (PIP 6104), and A.N.P.C.y T (06–257). The funding sources had no involvement in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.

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Authors and Affiliations

  1. Laboratorio de Inmunogenética, Hospital de Clínicas “José de San Martín”, Universidad de Buenos Aires, Av. Córdoba 2351. 3er piso, 1120, Buenos Aires, Argentina

    María Eugenia Inzaugarat, Nazarena Eugenia Ferreyra Solari, Luis Ariel Billordo & Alejandra Claudia Cherñavsky

  2. Unidad de Hepatología, Hospital Municipal de Gastroenterología “Dr. C.B. Udaondo”, Buenos Aires, Argentina

    Raquel Abecasis

  3. Sección de Hepatología y Transplante Hepático, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina

    Adrian C. Gadano

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  1. María Eugenia Inzaugarat
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  2. Nazarena Eugenia Ferreyra Solari
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  3. Luis Ariel Billordo
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  6. Alejandra Claudia Cherñavsky
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Correspondence to Alejandra Claudia Cherñavsky.

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Inzaugarat, M.E., Ferreyra Solari, N.E., Billordo, L.A. et al. Altered Phenotype and Functionality of Circulating Immune Cells Characterize Adult Patients with Nonalcoholic Steatohepatitis. J Clin Immunol 31, 1120–1130 (2011). https://doi.org/10.1007/s10875-011-9571-1

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  • DOI: https://doi.org/10.1007/s10875-011-9571-1

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