Quan Tang1, Karina R Gheorghe2, Xing-Mei Zhang3, Eva Lindroos4, Helene Alexanderson5, Cecilia Wick4, Mei Bruton4, Cátia Fernandes-Cerqueira4, Robert A Harris3, Inger Nennesmo6, Ingrid E Lundberg2. 1. Division of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, and Division of Rheumatology, Karolinska University Hospital, Solna, Stockholm, Sweden. quan.tang@ki.se. 2. Division of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, and Division of Rheumatology, Karolinska University Hospital, Solna, Stockholm, Sweden. 3. Applied Immunology and Immunotherapy, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska Hospital Solna, Stockholm, Sweden. 4. Division of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden. 5. 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. 6. Department of Pathology, Karolinska University Hospital, Stockholm, Sweden.
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.
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.
Authors: Uta Barbara Metzing; Christian von Loeffelholz; Ricardo Steidl; Bernd Romeike; René Winkler; Falk Rauchfuß; Utz Settmacher; Christian Stoppe; Sina M Coldewey; Claudia Weinmann; Martin O Weickert; Ralf A Claus; Andreas L Birkenfeld; Christian Kosan; Paul Horn Journal: Sci Rep Date: 2022-01-11 Impact factor: 4.379