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

Sheela Shrestha, Barry Wershil, John F. Sarwark, Timothy B. Niewold, Teresa Philipp, Lauren M. Pachman

Research output: Contribution to journalArticle

37 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2813-2822
Number of pages10
JournalArthritis and Rheumatism
Volume62
Issue number9
DOIs
StatePublished - 2010
Externally publishedYes

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Mast Cells
Dendritic Cells
Skin
Muscles
Pediatrics
Staining and Labeling
Interferon Type I
Exanthema
Juvenile dermatomyositis
Myxovirus Resistance Proteins
Cell Count
Biopsy
Tolonium Chloride
Staphylococcal Protein A
Nonparametric Statistics
Cell Differentiation
Blood Cells
Students
T-Lymphocytes
Antigens

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)
  • Medicine(all)

Cite this

Lesional and nonlesional skin from patients with untreated juvenile dermatomyositis displays increased numbers of mast cells and mature plasmacytoid dendritic cells. / Shrestha, Sheela; Wershil, Barry; Sarwark, John F.; Niewold, Timothy B.; Philipp, Teresa; Pachman, Lauren M.

In: Arthritis and Rheumatism, Vol. 62, No. 9, 2010, p. 2813-2822.

Research output: Contribution to journalArticle

Shrestha, Sheela ; Wershil, Barry ; Sarwark, John F. ; Niewold, Timothy B. ; Philipp, Teresa ; Pachman, Lauren M. / Lesional and nonlesional skin from patients with untreated juvenile dermatomyositis displays increased numbers of mast cells and mature plasmacytoid dendritic cells. In: Arthritis and Rheumatism. 2010 ; Vol. 62, No. 9. pp. 2813-2822.
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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.",
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T1 - Lesional and nonlesional skin from patients with untreated juvenile dermatomyositis displays increased numbers of mast cells and mature plasmacytoid dendritic cells

AU - Shrestha, Sheela

AU - Wershil, Barry

AU - Sarwark, John F.

AU - Niewold, Timothy B.

AU - Philipp, Teresa

AU - Pachman, Lauren M.

PY - 2010

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N2 - 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.

AB - 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.

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