PMID- 36195449
OWN - NLM
STAT- MEDLINE
DCOM- 20221116
LR  - 20221217
IS  - 1526-632X (Electronic)
IS  - 0028-3878 (Linking)
VI  - 99
IP  - 20
DP  - 2022 Nov 15
TI  - Morphologic and Molecular Patterns of Polymyositis With Mitochondrial Pathology 
      and Inclusion Body Myositis.
PG  - e2212-e2222
LID - 10.1212/WNL.0000000000201103 [doi]
AB  - BACKGROUND AND OBJECTIVE: To characterize morphological and molecular 
      underpinnings of polymyositis with mitochondrial pathology (PM-Mito) in 
      comparison with sporadic inclusion body myositis (IBM) and to define common and 
      distinct pathophysiologic features with a focus on interferon (IFN)-associated 
      inflammation and T-cell response. METHODS: In this cross-sectional study, 
      skeletal muscle biopsy samples and clinical and laboratory data from patients 
      with PM-Mito and IBM were analyzed at Charite university hospital in Berlin, 
      Germany. All available PM-Mito biopsy samples, an equal number of randomly 
      selected IBM biopsy samples, and randomly selected nondiseased controls (NDCs) 
      were included in the study. Biopsy samples were studied by histopathology, 
      immunohistochemistry, and quantitative PCR (qPCR) and compared with biopsies 
      derived from NDCs. Primary outcomes included cell counts for immunohistochemistry 
      and gene expression (fold-change values compared with those in NDCs) for qPCR. 
      RESULTS: Twenty-five skeletal muscle biopsy samples of patients with PM-Mito and 
      IBM were included in the study and compared with 5 biopsy samples from NDCs. 
      PM-Mito and IBM qualitatively harbored a strikingly similar molecular signature 
      and shared important histopathologic features. Expression of IFN-induced 
      guanylate-binding protein (GBP)6 and T-cell function-related KLRG1 distinguished 
      IBM from PM-Mito biopsies with IBM patients showing significantly higher 
      expression of GBP6 and KLRG1. Cryptic exon expression was detected in both 
      patient groups with IBM patients showing higher expression levels. Skeletal 
      muscle biopsies from IBM patients showed significantly more GBP6(+) cells and 
      KLRG1(+) lymphocytes in comparison with biopsies from patients with PM-Mito. 
      CD45(+), CD68(+), CD57(+), PD1(+), and CD8(+) cytotoxic T cells were also 
      significantly more abundant in patients with IBM. Clinically, patients with 
      PM-Mito presented with a spectrum of muscle-related symptoms including myalgia, 
      proximal paraparesis, proximal tetraparesis, and incomplete IBM-like patterns. 
      Thirteen of 14 (93%) patients with PM-Mito for whom clinical follow-up was 
      available later developed clinically defined IBM. Notably, 2 follow-up biopsies 
      obtained 5 and 7 years after the first ones were available in this cohort, both 
      showing histopathologic progress to net IBM including GBP6 and KLRG1 
      upregulation. DISCUSSION: Our combined data suggest that specific IFN-mediated 
      inflammation plays a key role in both IBM and PM-Mito. GBP6 was identified as a 
      new molecule of type II IFN-induced inflammation distinguishing IBM from PM-Mito. 
      Skeletal muscles from both groups harbor dysfunctional T cells of similar type, 
      albeit in different quantity. T-cell senescence exemplified by KLRG1 positivity 
      does not play a significant role in PM-Mito. Based on these findings, we propose 
      to include PM-Mito in the spectrum of IBM (IBM-spectrum disease [IBM-SD]) as a 
      possible early form of this disease. The establishment of IBM-SD as a larger 
      entity could potentially have a significant effect on the design of trials and 
      therapeutic interventions.
CI  - (c) 2022 American Academy of Neurology.
FAU - Kleefeld, Felix
AU  - Kleefeld F
AUID- ORCID: 0000-0002-0643-7313
AD  - From the Department of Neurology (F.K., W.S., K.H.), Charite-Universitatsmedizin 
      Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu 
      Berlin, Germany; Department of Neurology (A.U.), Tokyo Metropolitan Neurological 
      Hospital, Japan; Institute of Neuropathology (A.S., A.N.), Justus Liebig 
      University, Giessen, Germany; Pediatric Neurology (A.R.), University Children's 
      Hospital, University of Duisburg-Essen, Faculty of Medicine, Germany, and 
      Department of Neurology, Heimer Institute for Muscle Research, University 
      Hospital Bergmannsheil, Ruhr-University Bochum, Germany; Departments of 
      Rheumatology (U.S.) and Neuropathology (H.H.G.), Charite-Universitatsmedizin 
      Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu 
      Berlin, Germany; Department of Neuropathology (H.H.G.), University Medical 
      Center, Mainz, Germany and Charite-Universitatsmedizin Berlin, Corporate Member 
      of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Germany; 
      Department of Neuropediatrics (M.S.), Charite-Universitatsmedizin Berlin, 
      Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, 
      Germany; Cand Department of Neurology with Institute for Translational Neurology 
      (C.P.), University Hospital Munster, Munster, Germany and Department of 
      Neuropathology (C.P., W.S.), Charite-Universitatsmedizin Berlin, Corporate Member 
      of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Germany.
FAU - Uruha, Akinori
AU  - Uruha A
AD  - From the Department of Neurology (F.K., W.S., K.H.), Charite-Universitatsmedizin 
      Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu 
      Berlin, Germany; Department of Neurology (A.U.), Tokyo Metropolitan Neurological 
      Hospital, Japan; Institute of Neuropathology (A.S., A.N.), Justus Liebig 
      University, Giessen, Germany; Pediatric Neurology (A.R.), University Children's 
      Hospital, University of Duisburg-Essen, Faculty of Medicine, Germany, and 
      Department of Neurology, Heimer Institute for Muscle Research, University 
      Hospital Bergmannsheil, Ruhr-University Bochum, Germany; Departments of 
      Rheumatology (U.S.) and Neuropathology (H.H.G.), Charite-Universitatsmedizin 
      Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu 
      Berlin, Germany; Department of Neuropathology (H.H.G.), University Medical 
      Center, Mainz, Germany and Charite-Universitatsmedizin Berlin, Corporate Member 
      of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Germany; 
      Department of Neuropediatrics (M.S.), Charite-Universitatsmedizin Berlin, 
      Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, 
      Germany; Cand Department of Neurology with Institute for Translational Neurology 
      (C.P.), University Hospital Munster, Munster, Germany and Department of 
      Neuropathology (C.P., W.S.), Charite-Universitatsmedizin Berlin, Corporate Member 
      of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Germany.
FAU - Schanzer, Anne
AU  - Schanzer A
AD  - From the Department of Neurology (F.K., W.S., K.H.), Charite-Universitatsmedizin 
      Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu 
      Berlin, Germany; Department of Neurology (A.U.), Tokyo Metropolitan Neurological 
      Hospital, Japan; Institute of Neuropathology (A.S., A.N.), Justus Liebig 
      University, Giessen, Germany; Pediatric Neurology (A.R.), University Children's 
      Hospital, University of Duisburg-Essen, Faculty of Medicine, Germany, and 
      Department of Neurology, Heimer Institute for Muscle Research, University 
      Hospital Bergmannsheil, Ruhr-University Bochum, Germany; Departments of 
      Rheumatology (U.S.) and Neuropathology (H.H.G.), Charite-Universitatsmedizin 
      Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu 
      Berlin, Germany; Department of Neuropathology (H.H.G.), University Medical 
      Center, Mainz, Germany and Charite-Universitatsmedizin Berlin, Corporate Member 
      of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Germany; 
      Department of Neuropediatrics (M.S.), Charite-Universitatsmedizin Berlin, 
      Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, 
      Germany; Cand Department of Neurology with Institute for Translational Neurology 
      (C.P.), University Hospital Munster, Munster, Germany and Department of 
      Neuropathology (C.P., W.S.), Charite-Universitatsmedizin Berlin, Corporate Member 
      of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Germany.
FAU - Nishimura, Anna
AU  - Nishimura A
AD  - From the Department of Neurology (F.K., W.S., K.H.), Charite-Universitatsmedizin 
      Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu 
      Berlin, Germany; Department of Neurology (A.U.), Tokyo Metropolitan Neurological 
      Hospital, Japan; Institute of Neuropathology (A.S., A.N.), Justus Liebig 
      University, Giessen, Germany; Pediatric Neurology (A.R.), University Children's 
      Hospital, University of Duisburg-Essen, Faculty of Medicine, Germany, and 
      Department of Neurology, Heimer Institute for Muscle Research, University 
      Hospital Bergmannsheil, Ruhr-University Bochum, Germany; Departments of 
      Rheumatology (U.S.) and Neuropathology (H.H.G.), Charite-Universitatsmedizin 
      Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu 
      Berlin, Germany; Department of Neuropathology (H.H.G.), University Medical 
      Center, Mainz, Germany and Charite-Universitatsmedizin Berlin, Corporate Member 
      of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Germany; 
      Department of Neuropediatrics (M.S.), Charite-Universitatsmedizin Berlin, 
      Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, 
      Germany; Cand Department of Neurology with Institute for Translational Neurology 
      (C.P.), University Hospital Munster, Munster, Germany and Department of 
      Neuropathology (C.P., W.S.), Charite-Universitatsmedizin Berlin, Corporate Member 
      of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Germany.
FAU - Roos, Andreas
AU  - Roos A
AD  - From the Department of Neurology (F.K., W.S., K.H.), Charite-Universitatsmedizin 
      Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu 
      Berlin, Germany; Department of Neurology (A.U.), Tokyo Metropolitan Neurological 
      Hospital, Japan; Institute of Neuropathology (A.S., A.N.), Justus Liebig 
      University, Giessen, Germany; Pediatric Neurology (A.R.), University Children's 
      Hospital, University of Duisburg-Essen, Faculty of Medicine, Germany, and 
      Department of Neurology, Heimer Institute for Muscle Research, University 
      Hospital Bergmannsheil, Ruhr-University Bochum, Germany; Departments of 
      Rheumatology (U.S.) and Neuropathology (H.H.G.), Charite-Universitatsmedizin 
      Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu 
      Berlin, Germany; Department of Neuropathology (H.H.G.), University Medical 
      Center, Mainz, Germany and Charite-Universitatsmedizin Berlin, Corporate Member 
      of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Germany; 
      Department of Neuropediatrics (M.S.), Charite-Universitatsmedizin Berlin, 
      Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, 
      Germany; Cand Department of Neurology with Institute for Translational Neurology 
      (C.P.), University Hospital Munster, Munster, Germany and Department of 
      Neuropathology (C.P., W.S.), Charite-Universitatsmedizin Berlin, Corporate Member 
      of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Germany.
FAU - Schneider, Udo
AU  - Schneider U
AD  - From the Department of Neurology (F.K., W.S., K.H.), Charite-Universitatsmedizin 
      Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu 
      Berlin, Germany; Department of Neurology (A.U.), Tokyo Metropolitan Neurological 
      Hospital, Japan; Institute of Neuropathology (A.S., A.N.), Justus Liebig 
      University, Giessen, Germany; Pediatric Neurology (A.R.), University Children's 
      Hospital, University of Duisburg-Essen, Faculty of Medicine, Germany, and 
      Department of Neurology, Heimer Institute for Muscle Research, University 
      Hospital Bergmannsheil, Ruhr-University Bochum, Germany; Departments of 
      Rheumatology (U.S.) and Neuropathology (H.H.G.), Charite-Universitatsmedizin 
      Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu 
      Berlin, Germany; Department of Neuropathology (H.H.G.), University Medical 
      Center, Mainz, Germany and Charite-Universitatsmedizin Berlin, Corporate Member 
      of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Germany; 
      Department of Neuropediatrics (M.S.), Charite-Universitatsmedizin Berlin, 
      Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, 
      Germany; Cand Department of Neurology with Institute for Translational Neurology 
      (C.P.), University Hospital Munster, Munster, Germany and Department of 
      Neuropathology (C.P., W.S.), Charite-Universitatsmedizin Berlin, Corporate Member 
      of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Germany.
FAU - Goebel, Hans H
AU  - Goebel HH
AD  - From the Department of Neurology (F.K., W.S., K.H.), Charite-Universitatsmedizin 
      Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu 
      Berlin, Germany; Department of Neurology (A.U.), Tokyo Metropolitan Neurological 
      Hospital, Japan; Institute of Neuropathology (A.S., A.N.), Justus Liebig 
      University, Giessen, Germany; Pediatric Neurology (A.R.), University Children's 
      Hospital, University of Duisburg-Essen, Faculty of Medicine, Germany, and 
      Department of Neurology, Heimer Institute for Muscle Research, University 
      Hospital Bergmannsheil, Ruhr-University Bochum, Germany; Departments of 
      Rheumatology (U.S.) and Neuropathology (H.H.G.), Charite-Universitatsmedizin 
      Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu 
      Berlin, Germany; Department of Neuropathology (H.H.G.), University Medical 
      Center, Mainz, Germany and Charite-Universitatsmedizin Berlin, Corporate Member 
      of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Germany; 
      Department of Neuropediatrics (M.S.), Charite-Universitatsmedizin Berlin, 
      Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, 
      Germany; Cand Department of Neurology with Institute for Translational Neurology 
      (C.P.), University Hospital Munster, Munster, Germany and Department of 
      Neuropathology (C.P., W.S.), Charite-Universitatsmedizin Berlin, Corporate Member 
      of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Germany.
FAU - Schuelke, Markus
AU  - Schuelke M
AD  - From the Department of Neurology (F.K., W.S., K.H.), Charite-Universitatsmedizin 
      Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu 
      Berlin, Germany; Department of Neurology (A.U.), Tokyo Metropolitan Neurological 
      Hospital, Japan; Institute of Neuropathology (A.S., A.N.), Justus Liebig 
      University, Giessen, Germany; Pediatric Neurology (A.R.), University Children's 
      Hospital, University of Duisburg-Essen, Faculty of Medicine, Germany, and 
      Department of Neurology, Heimer Institute for Muscle Research, University 
      Hospital Bergmannsheil, Ruhr-University Bochum, Germany; Departments of 
      Rheumatology (U.S.) and Neuropathology (H.H.G.), Charite-Universitatsmedizin 
      Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu 
      Berlin, Germany; Department of Neuropathology (H.H.G.), University Medical 
      Center, Mainz, Germany and Charite-Universitatsmedizin Berlin, Corporate Member 
      of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Germany; 
      Department of Neuropediatrics (M.S.), Charite-Universitatsmedizin Berlin, 
      Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, 
      Germany; Cand Department of Neurology with Institute for Translational Neurology 
      (C.P.), University Hospital Munster, Munster, Germany and Department of 
      Neuropathology (C.P., W.S.), Charite-Universitatsmedizin Berlin, Corporate Member 
      of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Germany.
FAU - Hahn, Katrin
AU  - Hahn K
AD  - From the Department of Neurology (F.K., W.S., K.H.), Charite-Universitatsmedizin 
      Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu 
      Berlin, Germany; Department of Neurology (A.U.), Tokyo Metropolitan Neurological 
      Hospital, Japan; Institute of Neuropathology (A.S., A.N.), Justus Liebig 
      University, Giessen, Germany; Pediatric Neurology (A.R.), University Children's 
      Hospital, University of Duisburg-Essen, Faculty of Medicine, Germany, and 
      Department of Neurology, Heimer Institute for Muscle Research, University 
      Hospital Bergmannsheil, Ruhr-University Bochum, Germany; Departments of 
      Rheumatology (U.S.) and Neuropathology (H.H.G.), Charite-Universitatsmedizin 
      Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu 
      Berlin, Germany; Department of Neuropathology (H.H.G.), University Medical 
      Center, Mainz, Germany and Charite-Universitatsmedizin Berlin, Corporate Member 
      of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Germany; 
      Department of Neuropediatrics (M.S.), Charite-Universitatsmedizin Berlin, 
      Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, 
      Germany; Cand Department of Neurology with Institute for Translational Neurology 
      (C.P.), University Hospital Munster, Munster, Germany and Department of 
      Neuropathology (C.P., W.S.), Charite-Universitatsmedizin Berlin, Corporate Member 
      of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Germany.
FAU - Preusse, Corinna
AU  - Preusse C
AD  - From the Department of Neurology (F.K., W.S., K.H.), Charite-Universitatsmedizin 
      Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu 
      Berlin, Germany; Department of Neurology (A.U.), Tokyo Metropolitan Neurological 
      Hospital, Japan; Institute of Neuropathology (A.S., A.N.), Justus Liebig 
      University, Giessen, Germany; Pediatric Neurology (A.R.), University Children's 
      Hospital, University of Duisburg-Essen, Faculty of Medicine, Germany, and 
      Department of Neurology, Heimer Institute for Muscle Research, University 
      Hospital Bergmannsheil, Ruhr-University Bochum, Germany; Departments of 
      Rheumatology (U.S.) and Neuropathology (H.H.G.), Charite-Universitatsmedizin 
      Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu 
      Berlin, Germany; Department of Neuropathology (H.H.G.), University Medical 
      Center, Mainz, Germany and Charite-Universitatsmedizin Berlin, Corporate Member 
      of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Germany; 
      Department of Neuropediatrics (M.S.), Charite-Universitatsmedizin Berlin, 
      Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, 
      Germany; Cand Department of Neurology with Institute for Translational Neurology 
      (C.P.), University Hospital Munster, Munster, Germany and Department of 
      Neuropathology (C.P., W.S.), Charite-Universitatsmedizin Berlin, Corporate Member 
      of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Germany.
FAU - Stenzel, Werner
AU  - Stenzel W
AD  - From the Department of Neurology (F.K., W.S., K.H.), Charite-Universitatsmedizin 
      Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu 
      Berlin, Germany; Department of Neurology (A.U.), Tokyo Metropolitan Neurological 
      Hospital, Japan; Institute of Neuropathology (A.S., A.N.), Justus Liebig 
      University, Giessen, Germany; Pediatric Neurology (A.R.), University Children's 
      Hospital, University of Duisburg-Essen, Faculty of Medicine, Germany, and 
      Department of Neurology, Heimer Institute for Muscle Research, University 
      Hospital Bergmannsheil, Ruhr-University Bochum, Germany; Departments of 
      Rheumatology (U.S.) and Neuropathology (H.H.G.), Charite-Universitatsmedizin 
      Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu 
      Berlin, Germany; Department of Neuropathology (H.H.G.), University Medical 
      Center, Mainz, Germany and Charite-Universitatsmedizin Berlin, Corporate Member 
      of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Germany; 
      Department of Neuropediatrics (M.S.), Charite-Universitatsmedizin Berlin, 
      Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, 
      Germany; Cand Department of Neurology with Institute for Translational Neurology 
      (C.P.), University Hospital Munster, Munster, Germany and Department of 
      Neuropathology (C.P., W.S.), Charite-Universitatsmedizin Berlin, Corporate Member 
      of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Germany. 
      werner.stenzel@charite.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221004
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
SB  - IM
CIN - Neurology. 2022 Nov 15;99(20):873-874. PMID: 36195454
MH  - Humans
MH  - *Myositis, Inclusion Body/pathology
MH  - Cross-Sectional Studies
MH  - *Polymyositis
MH  - Muscle, Skeletal/pathology
MH  - Biopsy
MH  - Inflammation/pathology
MH  - *Myositis/pathology
EDAT- 2022/10/05 06:00
MHDA- 2022/11/18 06:00
CRDT- 2022/10/04 21:22
PHST- 2022/01/31 00:00 [received]
PHST- 2022/06/28 00:00 [accepted]
PHST- 2022/10/05 06:00 [pubmed]
PHST- 2022/11/18 06:00 [medline]
PHST- 2022/10/04 21:22 [entrez]
AID - WNL.0000000000201103 [pii]
AID - 10.1212/WNL.0000000000201103 [doi]
PST - ppublish
SO  - Neurology. 2022 Nov 15;99(20):e2212-e2222. doi: 10.1212/WNL.0000000000201103. 
      Epub 2022 Oct 4.