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Features of repeated muscle biopsies and phenotypes of monocytes in paired blood samples and clinical long-term response to treatment in patients with idiopathic inflammatory myopathy: a pilot study
Q. Tang1, K.R. Gheorghe2, X.-M. Zhang3, E. Lindroos4, H. Alexanderson5, C. Wick6, M. Bruton7, C. Fernandes-Cerqueira8, R.A. Harris9, I. Nennesmo10, I.E. Lundberg11
- Division of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, and Division of Rheumatology, Karolinska University Hospital, Solna, Stockholm, Sweden. quan.tang@ki.se
- Division of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, and Division of Rheumatology, Karolinska University Hospital, Solna, Stockholm, Sweden.
- Applied Immunology and Immunotherapy, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska Hospital Solna, Stockholm, Sweden.
- Division of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
- Division of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, and Functional Area Occupational Therapy and Physical Therapy, Karolinska University Hospital, and Dept.of NVS, Div. of Physiotherapy, Karolinska Inst., Stockholm, Sweden.
- Division of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
- Division of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
- Division of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
- Applied Immunology and Immunotherapy, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska Hospital Solna, Stockholm, Sweden.
- Department of Pathology, Karolinska University Hospital, Stockholm, Sweden.
- Division of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, and Division of Rheumatology, Karolinska University Hospital, Solna, Stockholm, Sweden.
CER11961
2020 Vol.38, N°1
PI 0042, PF 0049
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PMID: 31140400 [PubMed]
Received: 03/12/2018
Accepted : 04/03/2019
In Press: 22/05/2019
Published: 06/02/2020
Abstract
OBJECTIVES:
In a pilot study we aimed to identify biomarkers in repeated muscle biopsies and paired blood samples, taken before and after conventional immunosuppressive therapy, in order to predict long-term therapeutic response in patients with idiopathic inflammatory myopathies (IIM).
METHODS:
Muscle biopsies were selected from 13 new onset patients, six responders and seven non-responders. Repeated muscle biopsies after a median of 11 months follow-up were available from 9 patients and paired peripheral blood mononuclear cells (PBMCs) from 5 patients. Treatment response after 3 years was defined by MMT-8 measuring muscle strength and the ACR/EULAR 2016 improvement criteria. Frozen biopsy sections were immunohistochemically stained for expression of CD3, CD66b, IL-15, CD68, CD163 and myosin heavy chain neonatal (MHCn). PBMCs were analysed by flow cytometry for monocyte phenotypes (CD14, CD16, CD68, CX3CR1, and CCR2).
RESULTS:
Before treatment there were no significant differences in any clinical or muscle biopsy variables or monocyte subsets between responders and non-responders. MMT-8 was significantly higher compared to baseline in the responders at 3-year follow-up. In responders the expression of CD68 in the repeated biopsies was significantly lower compared to non-responders (p<0.05).
CONCLUSIONS:
Baseline biopsy, monocyte profile or clinical data did not predict long-term treatment response, but in the repeated biopsy within 1 year of immunosuppressive treatment, the lower number of macrophages (CD68+) seemed to predict a more favourable long-term clinical response with regard to improved muscle strength.