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- Pandya, Jayesh M., et al.
(author)
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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
- 2016
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In: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 18
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Journal article (peer-reviewed)abstract
- Background: 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. Methods: 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. Results: 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. Conclusions: 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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- Alexanderson, H, et al.
(author)
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Resistive home exercise in patients with recent-onset polymyositis and dermatomyositis -- a randomized controlled single-blinded study with a 2-year followup
- 2014
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In: The Journal of rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 41:6, s. 1124-1132
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Journal article (peer-reviewed)abstract
- To evaluate the outcome of resistive home exercise and its possible longterm influence on health, disability, and disease activity in patients with active polymyositis (PM) or dermatomyositis (DM).Methods.Nineteen patients with recent-onset PM/DM were included after introduction of high-dose prednisolone. They were assessed by independent assessors as to perceived health, muscle performance, aerobic capacity, and serum creatine phosphokinase (CPK) at baseline and after 24 weeks, including repeated muscle biopsies at 24 weeks (single-blinded randomized controlled study), and in an open-label followup at 52, 78, and 104 weeks. Patients were randomized to 12 weeks, 5 days/week resistive home exercise with telephone support and encouragement for another 12 weeks of twice-a-week home or gym exercise (EG, n = 10) or to 24 weeks, 5 days/week range of motion exercise (CG, n = 9). Patients in the CG group without inflammatory infiltrates in muscle biopsies at 24 weeks were invited to the 12-week resistive home exercises.Results.At baseline, the EG had poorer perceived health, but otherwise the groups were comparable. At 24 weeks, both groups improved in muscle performance and aerobic capacity (p < 0.001 to < 0.05) with no signs of increased inflammation assessed by CPK levels or muscle biopsies. Both groups improved in muscle performance and aerobic capacity up to 52 weeks (p < 0.05) lasting to 104 weeks in the EG (p < 0.05) and presented minor improvements in perceived health.Conclusion.Our study supports the safety of resistive exercise in patients with active PM/DM but did not reveal any between-group differences in exercise effects. An individually adapted physical therapist–supervised home exercise program might be recommended in early active PM/DM, with regular evaluation of muscle performance and health.
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