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

Clin Endocrinol (Oxf). 2013 Apr;78(4):621-8. doi: 10.1111/cen.12036.

Abstract

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 (CD24(high) CD38(high) CD19(+) 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use
  • Female
  • Hepatitis C / complications
  • Hepatitis C / drug therapy
  • Hepatitis C / immunology
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / adverse effects*
  • Interferon-alpha / therapeutic use
  • Lymphocyte Subsets / pathology*
  • Male
  • Melanoma / complications
  • Melanoma / drug therapy
  • Melanoma / immunology*
  • Melanoma / pathology
  • Middle Aged
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / therapeutic use
  • Skin Neoplasms / complications
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / immunology*
  • Skin Neoplasms / pathology
  • T-Lymphocytes, Regulatory / pathology*
  • Thyroid Function Tests
  • Thyroiditis / chemically induced*
  • Thyroiditis / immunology
  • Thyroiditis / pathology
  • Young Adult

Substances

  • Antiviral Agents
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins