title: CD45 is a more sensitive marker than CD3 to diagnose lymphocytic myocarditis in the endomyocardium.
abstract: To diagnose lymphocytic myocarditis (LM), immunohistopathological examination of endomyocardial biopsies (EMBs) is used with a cutoff value of at least 14 leukocytes per mm2, composed of CD3- and CD68-positive cells. We hypothesized that a more common leukocyte marker, CD45, instead of CD3 could increase the diagnostic sensitivity. Hearts of mice with acute viral myocarditis (n = 9) and of controls (n = 7) and the EMB sampling area of the left ventricular posterior wall (LVPW) obtained from autopsied hearts of patients diagnosed with LM (n = 18) and controls (n = 6) were stained with anti-CD68, anti-CD3, and anti-CD45. When applying the threshold of at least 14 leukocytes per mm2, 33% of the mice would be diagnosed with LM with the use of CD3+CD68 and 89% with the use of CD45+CD68. In the EMB sampling area of autopsied hearts, using the cutoff value of at least 14 leukocytes per mm2, CD3+CD68 could only confirm 17% of the diagnosis of LM, whereas CD45+CD68 could confirm 50% of the LM cases. Moreover, we compared inflammation in the EMB sampling area of the LVPW to the remaining myocardium of the LVPW and observed a significant increase of CD45+CD68 cells per mm2in patients with LM. In conclusion, the use of the common leukocyte marker CD45 increases the sensitivity of the diagnosis of LM. Furthermore, the inflammatory infiltrate in the EMB sampling area is significantly increased compared with the remaining LVPW, indicating that the sampling area constitutes the highest chance for histological diagnosis of LM.
authors.affiliation: Department of Pathology, VU University Medical Center, 1081 HV Amsterdam, the Netherlands; ICaR-VU, Institute for Cardiovascular Research, VU University Medical Center, 1081 HV Amsterdam, the Netherlands. Electronic address: l.woudstra@vumc.nl.
authors.forename: Linde
authors.initials: L
authors.lastname: Woudstra
authors.affiliation: ICaR-VU, Institute for Cardiovascular Research, VU University Medical Center, 1081 HV Amsterdam, the Netherlands; Department of Cardiology, VU University Medical Center, 1081 HV Amsterdam, the Netherlands; The Netherlands Heart Institute (ICIN), Inter university Cardiology Institute of the Netherlands, 3511 EP Utrecht, the Netherlands.
authors.forename: P Stefan
authors.initials: PS
authors.lastname: Biesbroek
authors.affiliation: Department of Pathology, VU University Medical Center, 1081 HV Amsterdam, the Netherlands; ICaR-VU, Institute for Cardiovascular Research, VU University Medical Center, 1081 HV Amsterdam, the Netherlands.
authors.forename: Reindert W
authors.initials: RW
authors.lastname: Emmens
authors.affiliation: Center for Heart Failure Research, Cardiovascular Research Institute Maastricht (CARIM), University Hospital Maastricht, 6229 ER Maastricht, the Netherlands.
authors.forename: Stephane
authors.initials: S
authors.lastname: Heymans
authors.affiliation: ICaR-VU, Institute for Cardiovascular Research, VU University Medical Center, 1081 HV Amsterdam, the Netherlands; Department of Cardiology, VU University Medical Center, 1081 HV Amsterdam, the Netherlands.
authors.forename: Lynda J
authors.initials: LJ
authors.lastname: Juffermans
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Allard C
authors.initials: AC
authors.lastname: van der Wal
authors.affiliation: ICaR-VU, Institute for Cardiovascular Research, VU University Medical Center, 1081 HV Amsterdam, the Netherlands; Department of Cardiology, VU University Medical Center, 1081 HV Amsterdam, the Netherlands; The Netherlands Heart Institute (ICIN), Inter university Cardiology Institute of the Netherlands, 3511 EP Utrecht, the Netherlands.
authors.forename: Albert C
authors.initials: AC
authors.lastname: van Rossum
authors.affiliation: Department of Pathology, VU University Medical Center, 1081 HV Amsterdam, the Netherlands; ICaR-VU, Institute for Cardiovascular Research, VU University Medical Center, 1081 HV Amsterdam, the Netherlands; Department of Cardiothoracic Surgery, VU University Medical Center, 1081 HV Amsterdam, the Netherlands.
authors.forename: Hans W M
authors.initials: HWM
authors.lastname: Niessen
authors.affiliation: Department of Pathology, VU University Medical Center, 1081 HV Amsterdam, the Netherlands; ICaR-VU, Institute for Cardiovascular Research, VU University Medical Center, 1081 HV Amsterdam, the Netherlands.
authors.forename: Paul A J
authors.initials: PAJ
authors.lastname: Krijnen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001344:Autopsy; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D017252:CD3 Complex / Q000032:analysis*; D016022:Case-Control Studies; D002648:Child; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000032:analysis*; D007958:Leukocyte Count; D008214:Lymphocytes / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D008809:Mice, Inbred C3H; D008875:Middle Aged; D009205:Myocarditis / Q000276:immunology* / Q000473:pathology; D009206:Myocardium / Q000276:immunology* / Q000473:pathology; D011237:Predictive Value of Tests; D011247:Pregnancy; D015203:Reproducibility of Results; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D017252:CD3 Complex; D017493:Leukocyte Common Antigens; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C081026:CD68 protein, mouse; C516769:PTPRC protein, human; C516770:Ptprc protein, mouse
keywords: CD3; CD45; Endomyocardial biopsy; Inflammatory cells; Lymphocytic myocarditis