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Effects of conventional immunosuppressive treatment on CD244+ (CD28null) and FOXP3+ T cells in the inflamed muscle of patients with polymyositis and dermatomyositis

Overview of attention for article published in Arthritis Research & Therapy, April 2016
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Title
Effects of conventional immunosuppressive treatment on CD244+ (CD28null) and FOXP3+ T cells in the inflamed muscle of patients with polymyositis and dermatomyositis
Published in
Arthritis Research & Therapy, April 2016
DOI 10.1186/s13075-016-0974-5
Pubmed ID
Authors

Jayesh M. Pandya, Ingela Loell, Mohammad Shahadat Hossain, Mei Zong, Helene Alexanderson, Sukanya Raghavan, Ingrid E. Lundberg, Vivianne Malmström

Abstract

T-cell infiltrates may persist in muscle tissue of polymyositis (PM) and dermatomyositis (DM) patients despite aggressive immunosuppressive treatment. Here, we investigated to what extent persistent T cells in affected muscle were FOXP3+, a marker for regulatory T cells (Tregs), or CD244+, a marker for CD28null T cells, and whether their presence correlated to clinical outcome. The sensitivity of CD28null T cells towards glucocorticoid and Treg-mediated immunosuppression was also investigated. Muscle biopsies from 16 newly diagnosed or untreated patients with PM/DM were investigated by immunohistochemistry for expression of CD3, FOXP3 and CD244 before and after treatment with glucocorticoids and immunosuppressive agents. For clinical evaluation, serum levels of creatine kinase, muscle performance (FI and MMT8), disease activity (MITAX) and disability (HAQ) were measured. In vitro suppressive effects of glucocorticoids and Tregs on T-cell activation were measured by CD69 upregulation. Before treatment, CD244+ cells were present at higher proportions compared to FOXP3+ cells in the inflamed muscle. Following treatment, FOXP3+ cell numbers decreased while CD244+ cells persisted. Patients with impaired muscle function (<75 % FI) post-treatment had higher levels of CD244+ cells in the follow-up biopsy compared to those with FI >75 %. MITAX and HAQ correlated with the number of CD244+ cells post-treatment. CD4+CD28null T cells displayed lower sensitivity towards both glucocorticoid and Treg-mediated immunosuppression in vitro compared to their CD28+ counterparts. Poor outcome in patients with myositis following immunosuppressive therapy was linked to persistence of CD244+ (CD28null) T cells in muscle tissue, suggesting their resistance against immunosuppression. A relative loss of regulatory T cells could also contribute to poor clinical outcome given their recently ascribed role in muscle tissue regeneration.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 41 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 2%
Unknown 40 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 15%
Researcher 6 15%
Student > Master 6 15%
Student > Doctoral Student 4 10%
Student > Bachelor 3 7%
Other 7 17%
Unknown 9 22%
Readers by discipline Count As %
Medicine and Dentistry 14 34%
Immunology and Microbiology 3 7%
Nursing and Health Professions 3 7%
Agricultural and Biological Sciences 2 5%
Biochemistry, Genetics and Molecular Biology 1 2%
Other 5 12%
Unknown 13 32%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 April 2016.
All research outputs
#20,655,488
of 25,373,627 outputs
Outputs from Arthritis Research & Therapy
#2,907
of 3,381 outputs
Outputs of similar age
#234,500
of 314,719 outputs
Outputs of similar age from Arthritis Research & Therapy
#28
of 37 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. This one is in the 10th percentile – i.e., 10% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,381 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.2. This one is in the 7th percentile – i.e., 7% of its peers scored the same or lower than it.
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