Immunopathogenesis of Pediatric Localized Scleroderma
Localized scleroderma (LS) is a complex disease characterized by a mixture of inflammation and fibrosis of the skin that, especially in the pediatric population, also affects extracutaneous tissues ranging from muscle to the central nervous system. Although developmental origins have been hypothesiz...
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doaj-e5bfae5480c14443b9a704ac3db0ae0b2020-11-24T22:15:53ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-04-011010.3389/fimmu.2019.00908452932Immunopathogenesis of Pediatric Localized SclerodermaKathryn S. Torok0Suzanne C. Li1Suzanne C. Li2Heidi M. Jacobe3Sarah F. Taber4Sarah F. Taber5Anne M. Stevens6Anne M. Stevens7Francesco Zulian8Theresa T. Lu9Theresa T. Lu10Theresa T. Lu11Division of Pediatric Rheumatology, Department of Pediatrics, Childrens's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, United StatesDivision of Pediatric Rheumatology, Department of Pediatrics, Hackensack University Medical Center, Hackensack, NJ, United StatesHackensack Meridian School of Medicine at Seton Hall University, Clifton, NJ, United StatesDepartment of Dermatology, UT Southwestern Medical Center, Dallas, TX, United StatesDivision of Pediatric Rheumatology, Department of Rheumatology, Hospital for Special Surgery, New York, NY, United StatesDepartment of Pediatrics, Weill Cornell Medicine, New York, NY, United StatesDivision of Pediatric Rheumatology, Department of Pediatrics, University of Washington, Seattle, WA, United StatesSeattle Children's Research Institute, University of Washington, Seattle, WA, United StatesPediatric Rheumatology Unit, Department of Woman's and Child's Health, University of Padua, Padua, ItalyDivision of Pediatric Rheumatology, Department of Rheumatology, Hospital for Special Surgery, New York, NY, United States0HSS Research Institute, Hospital for Special Surgery, New York, NY, United States1Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, United StatesLocalized scleroderma (LS) is a complex disease characterized by a mixture of inflammation and fibrosis of the skin that, especially in the pediatric population, also affects extracutaneous tissues ranging from muscle to the central nervous system. Although developmental origins have been hypothesized, evidence points to LS as a systemic autoimmune disorder, as there is a strong correlation to family history of autoimmune disease, the presence of shared HLA types with rheumatoid arthritis, high frequency of auto-antibodies, and elevated circulating chemokines and cytokines associated with T-helper cell, IFNγ, and other inflammatory pathways. This inflammatory phenotype of the peripheral blood is reflected in the skin via microarray, RNA Sequencing and tissue staining. Research is underway to identify the key players in the pathogenesis of LS, but close approximation of inflammatory lymphocytic and macrophage infiltrate with collagen and fibroblasts deposition supports the notion that LS is a disease of inflammatory driven fibrosis. The immune system is dynamic and undergoes changes during childhood, and we speculate on how the unique features of the immune system in childhood could potentially contribute to some of the differences in LS between children and adults. Interestingly, the immune phenotype in pediatric LS resembles to some extent the healthy adult cellular phenotype, possibly supporting accelerated maturation of the immune system in LS. We discuss future directions in better understanding the pathophysiology of and how to better treat pediatric LS.https://www.frontiersin.org/article/10.3389/fimmu.2019.00908/fulllocalized sclerodermamorpheapediatric rheumatologyimmunophenotypedisease etiologyautoimmune disease |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kathryn S. Torok Suzanne C. Li Suzanne C. Li Heidi M. Jacobe Sarah F. Taber Sarah F. Taber Anne M. Stevens Anne M. Stevens Francesco Zulian Theresa T. Lu Theresa T. Lu Theresa T. Lu |
spellingShingle |
Kathryn S. Torok Suzanne C. Li Suzanne C. Li Heidi M. Jacobe Sarah F. Taber Sarah F. Taber Anne M. Stevens Anne M. Stevens Francesco Zulian Theresa T. Lu Theresa T. Lu Theresa T. Lu Immunopathogenesis of Pediatric Localized Scleroderma Frontiers in Immunology localized scleroderma morphea pediatric rheumatology immunophenotype disease etiology autoimmune disease |
author_facet |
Kathryn S. Torok Suzanne C. Li Suzanne C. Li Heidi M. Jacobe Sarah F. Taber Sarah F. Taber Anne M. Stevens Anne M. Stevens Francesco Zulian Theresa T. Lu Theresa T. Lu Theresa T. Lu |
author_sort |
Kathryn S. Torok |
title |
Immunopathogenesis of Pediatric Localized Scleroderma |
title_short |
Immunopathogenesis of Pediatric Localized Scleroderma |
title_full |
Immunopathogenesis of Pediatric Localized Scleroderma |
title_fullStr |
Immunopathogenesis of Pediatric Localized Scleroderma |
title_full_unstemmed |
Immunopathogenesis of Pediatric Localized Scleroderma |
title_sort |
immunopathogenesis of pediatric localized scleroderma |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2019-04-01 |
description |
Localized scleroderma (LS) is a complex disease characterized by a mixture of inflammation and fibrosis of the skin that, especially in the pediatric population, also affects extracutaneous tissues ranging from muscle to the central nervous system. Although developmental origins have been hypothesized, evidence points to LS as a systemic autoimmune disorder, as there is a strong correlation to family history of autoimmune disease, the presence of shared HLA types with rheumatoid arthritis, high frequency of auto-antibodies, and elevated circulating chemokines and cytokines associated with T-helper cell, IFNγ, and other inflammatory pathways. This inflammatory phenotype of the peripheral blood is reflected in the skin via microarray, RNA Sequencing and tissue staining. Research is underway to identify the key players in the pathogenesis of LS, but close approximation of inflammatory lymphocytic and macrophage infiltrate with collagen and fibroblasts deposition supports the notion that LS is a disease of inflammatory driven fibrosis. The immune system is dynamic and undergoes changes during childhood, and we speculate on how the unique features of the immune system in childhood could potentially contribute to some of the differences in LS between children and adults. Interestingly, the immune phenotype in pediatric LS resembles to some extent the healthy adult cellular phenotype, possibly supporting accelerated maturation of the immune system in LS. We discuss future directions in better understanding the pathophysiology of and how to better treat pediatric LS. |
topic |
localized scleroderma morphea pediatric rheumatology immunophenotype disease etiology autoimmune disease |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2019.00908/full |
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