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Effects of immunosuppressive treatment on interleukin-15 and interleukin-15 receptor α expression in muscle tissue of patients with polymyositis or dermatomyositis
  1. Mei Zong1,2,
  2. Ingela Loell1,
  3. Eva Lindroos1,
  4. Gustavo A Nader1,
  5. Helene Alexanderson1,3,
  6. Christina Ståhl Hallengren4,
  7. Kristian Borg5,
  8. Snjolaug Arnardottir6,
  9. Iain B McInnes7,
  10. Ingrid E Lundberg1
  1. 1Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden
  2. 2Department of Rheumatology and Immunology, Shandong Provincial Hospital, Shandong University, Jinan 250021, China
  3. 3Department of Physical Therapy, Orthopaedic/Rheumatology Unit, Karolinska Univeristy Hospital, Solna, Karolinska Institutet, Stockholm, Sweden
  4. 4Rheumatology Unit, Helsingborg Hospital, Helsingborg, Sweden
  5. 5Division of Rehabilitation Medicine, Department of Clinical Sciences, Karolinska Institutet, Danderyd University Hospital, Stockholm, Sweden
  6. 6Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
  7. 7Centre for Rheumatic Diseases, University of Glasgow, Glasgow Royal Infirmary, Glasgow, UK
  1. Correspondence to Mei Zong, Rheumatology Unit, Karolinska University Hospital, SE-171 76, Stockholm, Sweden; mei.zong{at}ki.se

Abstract

Objectives To investigate the expression of interleukin (IL)-15 and IL-15 receptor α (IL-15Rα) in muscle tissue from patients with polymyositis or dermatomyositis before and after conventional immunosuppressive (IS) treatment.

Methods Muscle biopsies from 17 patients before and after conventional IS treatment and seven healthy individuals were investigated by immunohistochemistry using antibodies against IL-15 and IL-15Rα. Quantification was performed by computerised image analysis. Cellular localisation of IL-15 was determined by double immunofluorescence. Clinical outcome was measured by the functional index and serum creatine kinase. Human myotubes were cultured and IL-15 staining was performed by immunocytochemistry.

Results IL-15 was observed in mononuclear inflammatory cells of muscle tissue while IL-15Rα was localised to mononuclear inflammatory cells, capillaries and large vessels. Double staining showed localisation of IL-15 to CD163+ macrophages. A significantly larger number of IL-15 and IL-15Rα-positive cells were seen in muscle tissue of patients compared with healthy individuals. Baseline IL-15 expression correlated negatively with improvement in muscle function. After conventional IS treatment, a significantly lower number of IL-15 and IL-15Rα-positive cells was found. However, compared with controls, eight of 17 patients still had more IL-15-positive cells and less muscle function improvement was shown in this group of patients, both in short-term and long-term observations. Human differentiated myotubes were negative for IL-15 staining.

Conclusions IL-15 and its receptor are expressed in the muscle tissue of patients with myositis and IL-15 expression is correlated with improvement in muscle function. IL-15 may play a role in the pathogenesis of myositis and could be a biological treatment target, at least in a subgroup of patients with polymyositis or dermatomyositis.

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Footnotes

  • Funding This study was supported by grants from the Swedish Research Council, the Swedish Rheumatism Association, King Gustaf V 80 Year Foundation, Funds at the Karolinska Institutet and through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet.

  • Competing interests None.

  • Ethics approval Ethics approval for the research was granted by the ethics committee at Karolinska University Hospital, Stockholm and all patients and control individuals gave their informed consent to participate in the study.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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