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Immunophysiology of Pediatric Rheumatic Diseases

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Front. Immunol. | doi: 10.3389/fimmu.2019.00908

Immunopathogenesis of pediatric localized scleroderma

  • 1Children's Hospital of Pittsburgh, School of Medicine, University of Pittsburgh, United States
  • 2Hackensack University Medical Center, United States
  • 3University of Texas Southwestern Medical Center, United States
  • 4Hospital for Special Surgery, United States
  • 5Weill Cornell Medicine, Cornell University, United States
  • 6Seattle Children's Hospital, United States
  • 7University of Washington Medical Center, United States
  • 8University of Padova, Italy
  • 9Auotimmunity and Inflammation Program, Hospital for Special Surgery, United States

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. 

Keywords: scleroderma, pediatric, Immunopathogenesis, morphea, Linear scleroderma, immunophysiology, Pathogenesis

Received: 05 Feb 2019; Accepted: 09 Apr 2019.

Edited by:

Randy Q. Cron, University of Alabama at Birmingham, United States

Reviewed by:

Richard M. Silver, Medical University of South Carolina, United States
Ann M. Reed, School of Medicine, Duke University, United States  

Copyright: © 2019 Torok, Li, Jacobe, Taber, Stevens, Zulian and Lu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Theresa T. Lu, Hospital for Special Surgery, Auotimmunity and Inflammation Program, New York, 10021, NY, United States, lut@hss.edu