title: Regulatory T cells and other lymphocyte subpopulations in patients with melanoma developing interferon-induced thyroiditis during high-dose interferon-α2b treatment.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Department of Endocrinology and Nutrition, Hospital Universitari Germans Trias i Pujol, Universitat Autonoma de Barcelona, spain. bsoldevila.germanstrias@gencat.cat
authors.forename: Berta
authors.initials: B
authors.lastname: Soldevila
authors.forename: Núria
authors.initials: N
authors.lastname: Alonso
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Martínez-Arconada
authors.forename: Maria L
authors.initials: ML
authors.lastname: Granada
authors.forename: Aram
authors.initials: A
authors.lastname: Boada
authors.forename: Virginia
authors.initials: V
authors.lastname: Vallejos
authors.forename: Manuel
authors.initials: M
authors.lastname: Fraile
authors.forename: Marco A
authors.initials: MA
authors.lastname: Fernández-Sanmartín
authors.forename: Ricardo
authors.initials: R
authors.lastname: Pujol-Borrell
authors.forename: Manel
authors.initials: M
authors.lastname: Puig-Domingo
authors.forename: Anna
authors.initials: A
authors.lastname: Sanmartí
authors.forename: Eva M
authors.initials: EM
authors.lastname: Martínez-Cáceres
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D016131:Lymphocyte Subsets / Q000473:pathology*; D008297:Male; D008545:Melanoma / Q000150:complications / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000150:complications / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000473:pathology*; D013960:Thyroid Function Tests; D013966:Thyroiditis / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins