title: Lymphocytes infiltrate the quadriceps muscle in lymphocytic myocarditis patients: a potential new diagnostic tool.
abstract: BACKGROUND
  Diagnosing lymphocytic myocarditis (LM) is challenging because of the large variation in clinical presentation and the limitations inherent in current diagnostic tools. The objective of this study was to analyze infiltration of inflammatory cells in quadriceps skeletal muscle of LM patients and investigate the potential diagnostic value of assaying infiltrating inflammatory cells.
  
  
  METHODS
  Quadriceps muscle tissue, obtained at autopsy from control patients (n = 9) and LM patients (n = 21), was analyzed using immunohistochemistry for infiltration of lymphocytes (CD45), macrophages (CD68), neutrophilic granulocytes (myeloperoxidase), and several lymphocyte subtypes (CD3, CD4, CD8, CD20) and using polymerase chain reaction for a panel of myocarditis-associated viruses. Additionally, quadriceps muscle from mice with acute coxsackievirus B3-induced myocarditis and control mice was analyzed for presence of lymphocytes and virus.
  
  
  RESULTS
  In quadriceps muscle of LM patients the number of infiltrating lymphocytes were significantly increased and LM was diagnosed with specificity of 100% and sensitivity of 71%. Parvovirus B19 was the primary virus found in our patient groups, found in quadriceps tissue of 3 LM patients (although it was also found in 1 control patient). In the mice, enteroviral RNA was present in the quadriceps muscle, although enteroviral capsid proteins and lymphocyte infiltration were found primarily in the adipose tissue within and directly adjacent to the myocyte tissue, rather than in the myocyte tissue itself.
  
  
  CONCLUSIONS
  LM is associated with lymphocyte infiltration and viral presence in quadriceps muscle. This indicates that skeletal muscle biopsy/lymphocyte quantification might be a potential diagnostic tool for LM patients.
authors.affiliation: Department of Pathology, VU Medical Center, Amsterdam, The Netherlands; ICaR-VU, Institute of Cardiovascular Research, VU Medical Center, Amsterdam, The Netherlands; Department of Immunopathology, Sanquin Research, Amsterdam, The Netherlands. Electronic address: r.emmens@vumc.nl.
authors.forename: Reindert W
authors.initials: RW
authors.lastname: Emmens
authors.affiliation: Department of Pathology, VU Medical Center, Amsterdam, The Netherlands; ICaR-VU, Institute of Cardiovascular Research, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Linde
authors.initials: L
authors.lastname: Woudstra
authors.affiliation: Center for Heart Failure Research, Maastricht University, Maastricht, The Netherlands.
authors.forename: Anna
authors.initials: A
authors.lastname: Papageorgiou
authors.affiliation: Center for Heart Failure Research, Maastricht University, Maastricht, The Netherlands.
authors.forename: Paolo
authors.initials: P
authors.lastname: Carai
authors.affiliation: Department of Pathology, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Smit
authors.affiliation: Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Sevgi
authors.initials: S
authors.lastname: Seven-Deniz
authors.affiliation: Department of Pathology, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Rozendaal
authors.affiliation: ICaR-VU, Institute of Cardiovascular Research, VU Medical Center, Amsterdam, The Netherlands; Department of Physiology, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Paulus
authors.affiliation: Department of Immunopathology, Sanquin Research, Amsterdam, The Netherlands.
authors.forename: Diana
authors.initials: D
authors.lastname: Wouters
authors.affiliation: Department of Immunopathology, Sanquin Research, Amsterdam, The Netherlands; Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Sacha
authors.initials: S
authors.lastname: Zeerleder
authors.affiliation: Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Murk
authors.affiliation: Department of Immunopathology, Sanquin Research, Amsterdam, The Netherlands.
authors.forename: Marieke S
authors.initials: MS
authors.lastname: van Ham
authors.affiliation: Center for Heart Failure Research, Maastricht University, Maastricht, The Netherlands.
authors.forename: Stephane
authors.initials: S
authors.lastname: Heymans
authors.affiliation: ICaR-VU, Institute of Cardiovascular Research, VU Medical Center, Amsterdam, The Netherlands; Department of Cardiology, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Albert C
authors.initials: AC
authors.lastname: van Rossum
authors.affiliation: Department of Pathology, VU Medical Center, Amsterdam, The Netherlands; ICaR-VU, Institute of Cardiovascular Research, VU Medical Center, Amsterdam, The Netherlands; Department of Cardiac Surgery, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Hans W M
authors.initials: HW
authors.lastname: Niessen
authors.affiliation: Department of Pathology, VU Medical Center, Amsterdam, The Netherlands; ICaR-VU, Institute of Cardiovascular Research, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Paul A J
authors.initials: PA
authors.lastname: Krijnen
mesh_terms: D000818:Animals; D002102:Cadaver; D047630:Depsipeptides; D003937:Diagnosis, Differential; D004195:Disease Models, Animal; D005260:Female; D005500:Follow-Up Studies; D005670:Fusarium; D006801:Humans; D007150:Immunohistochemistry; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000473:pathology*; D051379:Mice; D008809:Mice, Inbred C3H; D009205:Myocarditis / Q000175:diagnosis*; D009206:Myocardium / Q000473:pathology*; D052097:Quadriceps Muscle / Q000473:pathology*; D012189:Retrospective Studies
chemical_list: D047630:Depsipeptides; C014001:fusafungin