T lymphocyte abnormalities in juvenile systemic sclerosis patients

Reiff, Andreas; Weinberg, Kenneth I.; Triche, Timothy J.; Masinsin, Bernadette; Mahadeo, Kris Michael; Lin, Chen‐Chou; Brown, Diane E.; Parkman, Robertson

doi:10.1016/j.clim.2013.07.005

Cited by 20 publications

(9 citation statements)

References 49 publications

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“…Debate on the pathogenesis of chronic GVHD has centered on whether chronic GVHD is a continuation of the pathogenic mechanisms that cause acute GVHD (ie, donor-derived T lymphocytes with specificity for recipient-restricted histocompatibility antigens/cytokines) or a disease of immune dysregulation [1][2][3]. The present demonstration of decreased rTregs in HSCT recipients with active chronic GVHD is similar to the reported deficiencies of rTregs in both adult and pediatric patients with systemic sclerosis, indicating that immune dysregulation may be central to the pathogenesis of both systemic sclerosis and chronic GVHD [24,25].…”

Section: Discussionsupporting

confidence: 76%

Immunologic Resolution of Human Chronic Graft-versus-Host Disease

Mahadeo

Masinsin

Kapoor

et al. 2014

Biology of Blood and Marrow Transplantation

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To determine the role of regulatory T lymphocytes (Tregs) in the pathogenesis of human chronic graft-versus-host disease (GVHD) and its clinical resolution, we evaluated long-term recipients of pediatric allogeneic hematopoietic stem cell transplantation (HSCT). Seventy-one recipients were evaluated, 30 of whom had a history of chronic GVHD, including 16 with active chronic GVHD and 14 with resolved chronic GVHD. There were no significant clinical differences and no differences in the frequency of Tregs (CD4(+), CD127(-), CD25(+)) between the recipients with active chronic GVHD and those with resolved chronic GVHD. Using the Miyara/Sakaguchi classification scheme to identify functional Tregs, a decreased frequency of functional resting Tregs (rTregs) was identified in recipients with active chronic GVHD (P = .009 compared with normal donors; P = .001 compared with HSCT recipients without history of chronic GVHD; P = .005 compared with recipients with resolved chronic GVHD). The frequency and number of recent thymic emigrants in rTregs were normal in recipients with resolved chronic GVHD, but persistently decreased in recipients with active chronic GVHD. These results support the hypothesis that the reestablishment of normal numbers of functional rTregs is required for the clinical resolution of chronic GVHD.

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Section: Discussionsupporting

confidence: 76%

Immunologic Resolution of Human Chronic Graft-versus-Host Disease

Mahadeo

Masinsin

Kapoor

et al. 2014

Biology of Blood and Marrow Transplantation

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“…The most dramatic reduction from inducing to functional Tregs was seen in the jSSc disease control. Reiff et al (2013) also observed significantly decreased numbers of functional Tregs in jSSc PBMCs, further supporting a more severe phenotype in SSc. The similar decrease in LS functional Tregs and their negative correlation with LS disease severity features implicates the permissive status of disease pathophysiology when functional Tregs populations are low.…”

mentioning

confidence: 56%

Identifying the Signature Immune Phenotypes Present in Pediatric Localized Scleroderma

Mirizio

Marathi

Hershey

et al. 2019

Journal of Investigative Dermatology

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“…Flow cytometry studies of the circulating cellular phenotype of LS (pediatric and adult) have shown a predominance of CD4 + T helper cells along with decreased functional T regulatory cells (61–63). This decrease in T regulatory cells, possibly reflecting a more “permissive state,” was also seen in pediatric SSc without increases in other T cell populations (64). Furthermore, when comparing paired active to inactive PBMC phenotypes in LS, those with active disease states demonstrated much higher populations of IFNγ-expressing T cells (reflecting T H 1 cells; CD4 + IFNγ + T cells) (63).…”

Section: Potential Pathogenic Etiologiesmentioning

confidence: 69%

Immunopathogenesis of Pediatric Localized Scleroderma

Torok

Jacobe

et al. 2019

Front. Immunol.

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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.

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T lymphocyte abnormalities in juvenile systemic sclerosis patients

Cited by 20 publications

References 49 publications

Immunologic Resolution of Human Chronic Graft-versus-Host Disease

Immunologic Resolution of Human Chronic Graft-versus-Host Disease

Identifying the Signature Immune Phenotypes Present in Pediatric Localized Scleroderma

Immunopathogenesis of Pediatric Localized Scleroderma

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