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Monocyte and Lymphocyte Activation and Regulation in Multiple Sclerosis Patients. Therapy Effects

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Abstract

Analysis of gut barrier status, monocyte and lymphocyte activation and T regulatory (Treg) cells at diagnosis before and after therapy, in patients with multiple sclerosis (MS). Analysis of differential effects of interferon beta (IFN-β), glatiramer acetate (GA) and natalizumab. Thirty-five patients with untreated MS were included. Gut barrier status (serum concentrations of intestinal fatty acid binding protein), monocyte (serum levels of soluble CD14, soluble CD163 and interleukin 6) and T lymphocyte activation (CD4 + DR+ and CD8 + DR+) and Treg (CD4 + CD25highFoxP3+) cells were analyzed. Patients with clinical isolated syndrome and relapsing-remitting forms were treated with IFN-β or GA, and immune characteristics were reevaluated following up after 6 months. A sample of 56 stable RR MS patients, in treatment with IFN-β, GA or natalizumab, and 50 healthy individuals were included as controls. Gut barrier status was similar in MS patients and healthy controls. Untreated patients with relapsing-remitting and primary progressive patterns of MS showed increased serum levels of soluble CD14. At baseline, significant increases in activated T lymphocytes and Treg were detected in patients. A significant decrease of CD4 + DR+, CD8 + DR+, and Treg percentages after 6 months of therapy was observed. In previously treated patients, IFN-β, GA, or natalizumab therapies were associated with a comparable cell proportion of activated lymphocytes and Treg. MS patients have a baseline state characterized by monocyte and lymphocyte activation, not related with gut barrier lesion. An increase in Treg number, correlated with activated T CD8+ lymphocytes, was detected. Treatment with IFN-β, GA or natalizumab was associated with a comparable decrease in activated lymphocytes and Treg.

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Contributions Made by each of the Authors to the Article

Conceived and designed the experiments: María Carmen González-Oria, Mercedes Márquez-Coello, José A Girón-González.

Clinical follow-up of patients`: María Carmen González-Oria, Joaquín Argente-Alcaraz, Miguel Moya-Molina.

Contributed reagents/materials/analysis tools: Mercedes Márquez-Coello; José Antonio Girón-González.

Analyzed the data: María Carmen González-Oria, José Antonio Girón-Ortega, José Antonio Girón-González.

Wrote the draft: José Antonio Girón-Ortega, José Antonio Girón-González.

All authors contributed to conception of the study, and critical revision of the manuscript, and saw and approved the final version.

Availability of Data and Materials

All data generated or analyzed during this study are included in this published article.

Funding

This work was supported by a Grant from Neurología, Fundación para la Investigación Biomédica de Cádiz. MCGO was the recipient of this Grant.

Author information

Authors and Affiliations

  1. Servicio de Neurología, Hospitales Universitarios Virgen del Rocío, Seville, Spain

    M. C. González-Oria

  2. Servicio de Medicina Interna, Hospital Universitario Puerta del Mar, Facultad de Medicina, Universidad de Cádiz, Instituto de Investigación e Innovación en Ciencias Biomédicas de Cádiz (INiBICA), Avda Ana de Viya s/n, 11009, Cádiz, Spain

    M. Márquez-Coello & José-Antonio Girón-González

  3. Servicio de Medicina Interna, Hospital Universitario Virgen Macarena, Seville, Spain

    J. A. Girón-Ortega

  4. Servicio de Neurología, Hospital Universitario Puerta del Mar, Facultad de Medicina, Universidad de Cádiz, Instituto de Investigación e Innovación en Ciencias Biomédicas de Cádiz (INiBICA), Cádiz, Spain

    J. Argente & M. Moya

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  1. M. C. González-Oria
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  2. M. Márquez-Coello
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  6. José-Antonio Girón-González
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Correspondence to José-Antonio Girón-González.

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The project was approved by the hospital ethical research committee. Written informed consent was obtained from each participant.

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The authors declare that they have no competing interests.

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González-Oria, M.C., Márquez-Coello, M., Girón-Ortega, J.A. et al. Monocyte and Lymphocyte Activation and Regulation in Multiple Sclerosis Patients. Therapy Effects. J Neuroimmune Pharmacol 14, 413–422 (2019). https://doi.org/10.1007/s11481-018-09832-z

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  • DOI: https://doi.org/10.1007/s11481-018-09832-z

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