Lesional and nonlesional skin from patients with untreated juvenile dermatomyositis displays increased numbers of mast cells and mature plasmacytoid dendritic cells

Arthritis Rheum. 2010 Sep;62(9):2813-22. doi: 10.1002/art.27529.

Abstract

Objective: To investigate the distribution of mast cells and dendritic cell (DC) subsets in paired muscle and skin (lesional/nonlesional) from untreated children with juvenile dermatomyositis (DM).

Methods: Muscle and skin biopsy samples (4 skin biopsy samples with active rash) from 7 patients with probable/definite juvenile DM were compared with muscle and skin samples from 10 healthy pediatric controls. Mast cell distribution and number were assessed by toluidine blue staining and analyzed by Student's t-test. Immunohistochemical analysis was performed to identify mature DCs, myeloid DCs (MDCs), and plasmacytoid DCs (PDCs) by using antibodies against DC-LAMP, blood dendritic cell antigen 1 (BDCA-1), and BDCA-2, respectively. Myxovirus resistance protein A (MxA) staining indicated active type I interferon (IFN) signaling; positive staining was scored semiquantitatively and analyzed using the Mann-Whitney U test.

Results: Both inflamed and nonlesional skin from patients with juvenile DM contained more mast cells than did skin from pediatric controls (P = 0.029), and comparable numbers of mast cells were present in lesional and nonlesional skin. Interestingly, mast cell numbers were greater in skin than in paired muscle tissue from patients with juvenile DM (P = 0.014) and were not increased in muscle from patients with juvenile DM compared with control muscle. Both muscle and skin from patients with juvenile DM showed more mature PDCs and MxA staining than did their corresponding control tissues (P < 0.05). In both muscle and skin from patients with juvenile DM and in pediatric control muscle, there were fewer MDCs than PDCs, and the distributions of MDCs and PDCs were similar in pediatric control skin samples.

Conclusion: The identification of mast cells in skin (irrespective of rash) from patients with juvenile DM, but not in paired muscle tissue, suggests that they have a specific role in juvenile DM skin pathophysiology. In skin from patients with juvenile DM, increased numbers of PDCs and increased expression of type I IFN-induced protein suggest a selective influence on T cell differentiation and subsequent effector function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism
  • Biopsy
  • Child, Preschool
  • Dendritic Cells / metabolism
  • Dendritic Cells / pathology*
  • Dermatomyositis / metabolism
  • Dermatomyositis / pathology*
  • Dermatomyositis / physiopathology
  • Female
  • GTP-Binding Proteins / metabolism
  • Humans
  • Interferon Type I / metabolism
  • Magnetic Resonance Imaging
  • Male
  • Mast Cells / metabolism
  • Mast Cells / pathology*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology*
  • Myxovirus Resistance Proteins
  • Polymorphism, Genetic
  • Severity of Illness Index
  • Signal Transduction
  • Skin / metabolism
  • Skin / pathology*
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Biomarkers
  • Interferon Type I
  • MX1 protein, human
  • Myxovirus Resistance Proteins
  • Tumor Necrosis Factor-alpha
  • GTP-Binding Proteins