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Clinical Endocrinology

Regulatory T cells and other lymphocyte subpopulations in patients with melanoma developing interferon-induced thyroiditis during high-dose interferon-α2b treatment

Authors

  • Berta Soldevila,

    Corresponding author
    1. Department of Medicine, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona
    2. Institut d'Investigació Germans Trias I Pujol
    • Department of Endocrinology and Nutrition, Hospital Universitari Germans Trias i Pujol
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  • Núria Alonso,

    1. Department of Endocrinology and Nutrition, Hospital Universitari Germans Trias i Pujol
    2. Department of Medicine, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona
    3. Institut d'Investigació Germans Trias I Pujol
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  • Maria J. Martínez-Arconada,

    1. Institut d'Investigació Germans Trias I Pujol
    2. Department of Immunology, Laboratory of Immunobiology for Research and Diagnosis (LIRAD), Blood and Tissue Bank, Hospital Universitari Germans Trias i Pujol
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  • Maria L. Granada,

    1. Department of Clinical Biochemistry, Hospital Universitari Germans Trias i Pujol
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  • Aram Boada,

    1. Department of Dermatology, Hospital Universitari Germans Trias i Pujol
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  • Virginia Vallejos,

    1. Department of Nuclear Medicine, Hospital Universitari Germans Trias i Pujol
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  • Manuel Fraile,

    1. Department of Nuclear Medicine, Hospital Universitari Germans Trias i Pujol
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  • Marco A. Fernández-Sanmartín,

    1. Institut d'Investigació Germans Trias I Pujol
    2. Cytometry Platform, Institut d'Investigació Germans Trias i Pujol
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  • Ricardo Pujol-Borrell,

    1. Institut d'Investigació Germans Trias I Pujol
    2. Department of Immunology, Laboratory of Immunobiology for Research and Diagnosis (LIRAD), Blood and Tissue Bank, Hospital Universitari Germans Trias i Pujol
    3. Department of Cell Biology, Physiology and Immunology, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, spain
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  • Manel Puig-Domingo,

    1. Department of Endocrinology and Nutrition, Hospital Universitari Germans Trias i Pujol
    2. Department of Medicine, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona
    3. Institut d'Investigació Germans Trias I Pujol
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  • Anna Sanmartí,

    1. Department of Endocrinology and Nutrition, Hospital Universitari Germans Trias i Pujol
    2. Department of Medicine, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona
    3. Institut d'Investigació Germans Trias I Pujol
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    • Shared senior co-authorship.

  • Eva M. Martínez-Cáceres

    1. Institut d'Investigació Germans Trias I Pujol
    2. Department of Immunology, Laboratory of Immunobiology for Research and Diagnosis (LIRAD), Blood and Tissue Bank, Hospital Universitari Germans Trias i Pujol
    3. Department of Cell Biology, Physiology and Immunology, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, spain
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    • Shared senior co-authorship.


Correspondence: Berta Soldevila, Department of Endocrinology and Nutrition, Hospital Universitari Germans Trias i Pujol, Carretera del Canyet s/n, 08916 Badalona, Barcelona, Spain. Tel.: +34934978860; Fax: +34934978843; E-mail: bsoldevila.germanstrias@gencat.cat

Summary

Context

One of the side effects of interferon-alpha therapy is interferon-induced thyroiditis (IIT). The role of lymphocyte subpopulations in IIT melanoma patients remains to be defined.

Objective

Our objective was to assess different peripheral blood lymphocyte subpopulations, mainly regulatory T cells (Tregs), in melanoma patients who developed IIT.

Design, patients and methods

From 30 melanoma patients receiving high-dose interferon (HDI)-alpha 2b (IFN-α2b) treatment, those who developed IIT (IIT patients) were selected and compared with patients who did not develop IIT (Co-MM) and healthy controls (Co-H). Peripheral blood mononuclear cells were obtained before treatment (BT), mid-treatment (MT), end of treatment (ET), 24 weeks post-treatment and at appearance of IIT (TT).

Results

Nine patients developed IIT (30%): four Hashimoto's thyroiditis and five destructive thyroiditis. An increase in Tregs was observed in both melanoma groups during HDI treatment. A decrease in CD3+, NKT lymphocyte subpopulations and Bcl2 expression on B cells was also observed in both groups. However, no changes were observed in the percentage of CD4+, CD8+, CD3+γδ+, CD19+, transitional B cells (CD24highCD38highCD19+CD27), natural killer (NK), invariant NKT (iNKT) lymphocytes and Th1/Th2 balance when BT was compared with ET. At TT, IIT patients had a higher Tregs percentage than Co-MM (P = 0·012) and Co-H (P = 0·004), a higher iNKT percentage than Co-MM (P = 0·011), a higher transitional B cells percentage than Co-H (P = 0·015), a lower CD3+ percentage than Co-H (P = 0·001) and a lower Bcl2 expression on B cells than Co-H (P < 0·001).

Conclusions

Our results point to the immunomodulatory effects of IFN-α on different lymphocyte subpopulations and a possible role of Tregs in melanoma patients who developed IIT.

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