Skip to main content
Top
Published in: Pediatric Cardiology 8/2011

01-12-2011 | Original Article

The Myocardium of Fetuses with Endocardial Fibroelastosis Contains Fewer B and T Lymphocytes than Normal Control Myocardium

Authors: Nisha M. Fernandes, Glenn P. Taylor, Cedric Manlhiot, Brian W. McCrindle, Michael Ho, Steven E. S. Miner, Adelle Atkinson, Edgar T. Jaeggi, Lynne E. Nield

Published in: Pediatric Cardiology | Issue 8/2011

Login to get access

Abstract

The observation that endocardial fibroelastosis (EFE) can result from an immune response to maternal autoantibody deposition in the fetal myocardium raises the possibility that the fetal immune system may contribute to the pathogenesis of idiopathic EFE and dilated cardiomyopathy (DCM). This study sought to characterize myocardial immune cell presence in fetuses and neonates with idiopathic EFE + DCM, in those with EFE + structural heart disease, and in normal control subjects. Paraffin tissue sections from fetuses identified from the pathology database were stained for B cell, T cell, macrophage, and general hematopoietic cell surface markers. Of the 14 fetuses included in the study, 5 had EFE + DCM, 4 had EFE + structural heart disease, and 5 were normal control fetuses. The EFE + DCM group had fewer B cells than the control group (0.15 vs. 0.44 cells/mm2; p = 0.005). The EFE + heart disease group had both fewer B cells (0.18 vs. 0.44 cells/mm2; p = 0.08) and T cells (0.29 vs. 0.80 cells/mm2; p = 0.04) than the control group. The CD4/CD8 ratio was similar in the EFE + DCM and EFE + heart disease groups (1.0 vs. 0.9; p = 0.17) but higher in the EFE + DCM group than in the control group (0.9 vs. 0.3; p = 0.03). The myocardium of fetuses with EFE contains fewer B and T lymphocytes than normal control fetuses.
Literature
1.
go back to reference Ait-Oufella H, Salomon BL, Potteaux S, Robertson AK, Gourdy P, Zoll J, Merval R, Esposito B, Cohen JL, Fisson S, Flavell RA, Hansson GK, Klatzmann D, Tedgui A, Mallat Z (2006) Natural regulatory T cells control the development of atherosclerosis in mice. Nat Med 12:178–180PubMedCrossRef Ait-Oufella H, Salomon BL, Potteaux S, Robertson AK, Gourdy P, Zoll J, Merval R, Esposito B, Cohen JL, Fisson S, Flavell RA, Hansson GK, Klatzmann D, Tedgui A, Mallat Z (2006) Natural regulatory T cells control the development of atherosclerosis in mice. Nat Med 12:178–180PubMedCrossRef
2.
go back to reference Bacchetta R, Gregori S, Roncarolo MG (2005) CD4+ regulatory T cells: mechanisms of induction and effector function. Autoimmun Rev 4:491–496PubMedCrossRef Bacchetta R, Gregori S, Roncarolo MG (2005) CD4+ regulatory T cells: mechanisms of induction and effector function. Autoimmun Rev 4:491–496PubMedCrossRef
3.
go back to reference Bauer M, Orescovic I, Schoell WM, Bianchi DW, Pertl B (2002) Detection of maternal deoxyribonucleic acid in umbilical cord plasma by using fluorescent polymerase chain reaction amplification of short tandem repeat sequences. Am J Obstet Gynecol 186:117–120PubMedCrossRef Bauer M, Orescovic I, Schoell WM, Bianchi DW, Pertl B (2002) Detection of maternal deoxyribonucleic acid in umbilical cord plasma by using fluorescent polymerase chain reaction amplification of short tandem repeat sequences. Am J Obstet Gynecol 186:117–120PubMedCrossRef
4.
go back to reference Bennett MJ, Hale DE, Pollitt RJ, Stanley CA, Variend S (1996) Endocardial fibroelastosis and primary carnitine deficiency due to a defect in the plasma membrane carnitine transporter. Clin Cardiol 19:243–246PubMedCrossRef Bennett MJ, Hale DE, Pollitt RJ, Stanley CA, Variend S (1996) Endocardial fibroelastosis and primary carnitine deficiency due to a defect in the plasma membrane carnitine transporter. Clin Cardiol 19:243–246PubMedCrossRef
5.
go back to reference Bonvicini F, Manaresi E, Gallinella G, Gentilomi GA, Musiani M, Zerbini M (2009) Diagnosis of fetal parvovirus B19 infection: value of virological assays in fetal specimens. BJOG 116:813–817PubMedCrossRef Bonvicini F, Manaresi E, Gallinella G, Gentilomi GA, Musiani M, Zerbini M (2009) Diagnosis of fetal parvovirus B19 infection: value of virological assays in fetal specimens. BJOG 116:813–817PubMedCrossRef
6.
go back to reference Burch GE, DePasquale NP, Sun SC, Hale AR, Mogabgab WJ (1966) Experimental Coxsackie virus endocarditis. JAMA 196:349–352PubMedCrossRef Burch GE, DePasquale NP, Sun SC, Hale AR, Mogabgab WJ (1966) Experimental Coxsackie virus endocarditis. JAMA 196:349–352PubMedCrossRef
7.
go back to reference Caddell JL (2001) Endomyocardial fibroelastosis. In: Allen HD, Clark EB, Gutgesell HP, Driscoll DJ (eds) Moss and Adams’ heart disease in infants, children and adolescents. Lippincott Williams & Wilkins, Philadelphia, pp 1272–1274 Caddell JL (2001) Endomyocardial fibroelastosis. In: Allen HD, Clark EB, Gutgesell HP, Driscoll DJ (eds) Moss and Adams’ heart disease in infants, children and adolescents. Lippincott Williams & Wilkins, Philadelphia, pp 1272–1274
8.
go back to reference Cupedo T, Nagasawa M, Weijer K, Blom B, Spits H (2005) Development and activation of regulatory T cells in the human fetus. Eur J Immunol 35:383–390PubMedCrossRef Cupedo T, Nagasawa M, Weijer K, Blom B, Spits H (2005) Development and activation of regulatory T cells in the human fetus. Eur J Immunol 35:383–390PubMedCrossRef
9.
go back to reference Fishbein MC, Ferrans VJ, Roberts WC (1977) Histologic and ultrastructural features of primary and secondary endocardial fibroelastosis. Arch Pathol Lab Med 101:49–54PubMed Fishbein MC, Ferrans VJ, Roberts WC (1977) Histologic and ultrastructural features of primary and secondary endocardial fibroelastosis. Arch Pathol Lab Med 101:49–54PubMed
10.
go back to reference Greenwood RD, Nadas AS, Fyler DC (1976) The clinical course of primary myocardial disease in infants and children. Am Heart J 92:549–560PubMedCrossRef Greenwood RD, Nadas AS, Fyler DC (1976) The clinical course of primary myocardial disease in infants and children. Am Heart J 92:549–560PubMedCrossRef
11.
go back to reference Griffin L, Kearney D, Ni J, Jaffe R, Fricker FJ, Webber S, Demmler G, Gelb BD, Towbin JA (1995) Analysis of formalin-fixed and frozen myocardial autopsy samples for viral genome in childhood myocarditis and dilated cardiomyopathy with endocardial fibroelastosis using polymerase chain reaction (PCR). Cardiovasc Pathol 4:3–11CrossRef Griffin L, Kearney D, Ni J, Jaffe R, Fricker FJ, Webber S, Demmler G, Gelb BD, Towbin JA (1995) Analysis of formalin-fixed and frozen myocardial autopsy samples for viral genome in childhood myocarditis and dilated cardiomyopathy with endocardial fibroelastosis using polymerase chain reaction (PCR). Cardiovasc Pathol 4:3–11CrossRef
12.
go back to reference Heller EA, Liu E, Tager AM, Yuan Q, Lin AY, Ahluwalia N, Jones K, Koehn SL, Lok VM, Aikawa E, Moore KJ, Luster AD, Gerszten RE (2006) Chemokine CXCL10 promotes atherogenesis by modulating the local balance of effector and regulatory T cells. Circulation 113:2301–2312PubMedCrossRef Heller EA, Liu E, Tager AM, Yuan Q, Lin AY, Ahluwalia N, Jones K, Koehn SL, Lok VM, Aikawa E, Moore KJ, Luster AD, Gerszten RE (2006) Chemokine CXCL10 promotes atherogenesis by modulating the local balance of effector and regulatory T cells. Circulation 113:2301–2312PubMedCrossRef
13.
go back to reference Henning RJ, Shariff M, Eadula U, Alvarado F, Vasko M, Sanberg PR, Delostia V (2008) Human cord blood mononuclear cells decrease cytokines and inflammatory cells in acute myocardial infarction. Stem Cells Dev 17:1207–1219PubMedCrossRef Henning RJ, Shariff M, Eadula U, Alvarado F, Vasko M, Sanberg PR, Delostia V (2008) Human cord blood mononuclear cells decrease cytokines and inflammatory cells in acute myocardial infarction. Stem Cells Dev 17:1207–1219PubMedCrossRef
14.
go back to reference Ino T, Benson LN, Freedom RM, Rowe RD (1988) Natural history and prognostic risk factors in endocardial fibroelastosis. Am J Cardiol 62:431–434PubMedCrossRef Ino T, Benson LN, Freedom RM, Rowe RD (1988) Natural history and prognostic risk factors in endocardial fibroelastosis. Am J Cardiol 62:431–434PubMedCrossRef
15.
go back to reference Jaeggi ET, Fouron JC, Silverman ED, Ryan G, Smallhorn J, Hornberger LK (2004) Transplacental fetal treatment improves the outcome of prenatally diagnosed complete atrioventricular block without structural heart disease. Circulation 110:1542–1548PubMedCrossRef Jaeggi ET, Fouron JC, Silverman ED, Ryan G, Smallhorn J, Hornberger LK (2004) Transplacental fetal treatment improves the outcome of prenatally diagnosed complete atrioventricular block without structural heart disease. Circulation 110:1542–1548PubMedCrossRef
16.
go back to reference Jaeggi ET, Silverman ED, Yoo SJ, Kingdom J (2004) Is immune-mediated complete fetal atrioventricular block reversible by transplacental dexamethasone therapy? Ultrasound Obstet Gynecol 23:602–605PubMedCrossRef Jaeggi ET, Silverman ED, Yoo SJ, Kingdom J (2004) Is immune-mediated complete fetal atrioventricular block reversible by transplacental dexamethasone therapy? Ultrasound Obstet Gynecol 23:602–605PubMedCrossRef
17.
go back to reference Klein RM, Jiang H, Niederacher D, Adams O, Du M, Horlitz M, Schley P, Marx R, Lankisch MR, Brehm MU, Strauer BE, Gabbert HE, Scheffold T, Gulker H (2004) Frequency and quantity of the parvovirus B19 genome in endomyocardial biopsies from patients with suspected myocarditis or idiopathic left ventricular dysfunction. Z Kardiol 93:300–309PubMedCrossRef Klein RM, Jiang H, Niederacher D, Adams O, Du M, Horlitz M, Schley P, Marx R, Lankisch MR, Brehm MU, Strauer BE, Gabbert HE, Scheffold T, Gulker H (2004) Frequency and quantity of the parvovirus B19 genome in endomyocardial biopsies from patients with suspected myocarditis or idiopathic left ventricular dysfunction. Z Kardiol 93:300–309PubMedCrossRef
18.
go back to reference Lipshultz SE, Sleeper LA, Towbin JA, Lowe AM, Orav EJ, Cox GF, Lurie PR, McCoy KL, McDonald MA, Messere JE, Colan SD (2003) The incidence of pediatric cardiomyopathy in two regions of the United States. N Engl J Med 348:1647–1655PubMedCrossRef Lipshultz SE, Sleeper LA, Towbin JA, Lowe AM, Orav EJ, Cox GF, Lurie PR, McCoy KL, McDonald MA, Messere JE, Colan SD (2003) The incidence of pediatric cardiomyopathy in two regions of the United States. N Engl J Med 348:1647–1655PubMedCrossRef
19.
go back to reference Maisch B, Herzum M, Hufnagel G, Schonian U (1996) Immunosuppressive and immunomodulatory treatment for myocarditis. Curr Opin Cardiol 11:310–324PubMedCrossRef Maisch B, Herzum M, Hufnagel G, Schonian U (1996) Immunosuppressive and immunomodulatory treatment for myocarditis. Curr Opin Cardiol 11:310–324PubMedCrossRef
20.
go back to reference Murphy K, Travers P, Walport M (2008) Janeway’s immunobiology. Garland Science, London, pp 783–803 Murphy K, Travers P, Walport M (2008) Janeway’s immunobiology. Garland Science, London, pp 783–803
21.
go back to reference Nield LE, Silverman ED, Smallhorn JF, Taylor GP, Mullen JB, Benson LN, Hornberger LK (2002) Endocardial fibroelastosis associated with maternal anti-Ro and anti-La antibodies in the absence of atrioventricular block. J Am Coll Cardiol 40:796–802PubMedCrossRef Nield LE, Silverman ED, Smallhorn JF, Taylor GP, Mullen JB, Benson LN, Hornberger LK (2002) Endocardial fibroelastosis associated with maternal anti-Ro and anti-La antibodies in the absence of atrioventricular block. J Am Coll Cardiol 40:796–802PubMedCrossRef
22.
go back to reference Nield LE, Silverman ED, Taylor GP, Smallhorn JF, Mullen JB, Silverman NH (2002) Maternal anti-Ro and anti-La antibody-associated endocardial fibroelastosis. Circulation 105:843–848PubMedCrossRef Nield LE, Silverman ED, Taylor GP, Smallhorn JF, Mullen JB, Silverman NH (2002) Maternal anti-Ro and anti-La antibody-associated endocardial fibroelastosis. Circulation 105:843–848PubMedCrossRef
23.
go back to reference Pahwa S, Read JS, Yin W, Matthews Y, Shearer W, Diaz C, Rich K, Mendez H, Thompson B (2008) CD4+/CD8+ T cell ratio for diagnosis of HIV-1 infection in infants: Women and Infants Transmission Study. Pediatrics 122:331–339PubMedCrossRef Pahwa S, Read JS, Yin W, Matthews Y, Shearer W, Diaz C, Rich K, Mendez H, Thompson B (2008) CD4+/CD8+ T cell ratio for diagnosis of HIV-1 infection in infants: Women and Infants Transmission Study. Pediatrics 122:331–339PubMedCrossRef
24.
go back to reference Pedra SR, Smallhorn JF, Ryan G, Chitayat D, Taylor GP, Khan R, Abdolell M, Hornberger LK (2002) Fetal cardiomyopathies: pathogenic mechanisms, hemodynamic findings, and clinical outcome. Circulation 106:585–591PubMedCrossRef Pedra SR, Smallhorn JF, Ryan G, Chitayat D, Taylor GP, Khan R, Abdolell M, Hornberger LK (2002) Fetal cardiomyopathies: pathogenic mechanisms, hemodynamic findings, and clinical outcome. Circulation 106:585–591PubMedCrossRef
25.
go back to reference Petit T, Dommergues M, Socie G, Dumez Y, Gluckman E, Brison O (1997) Detection of maternal cells in human fetal blood during the third trimester of pregnancy using allele-specific PCR amplification. Br J Haematol 98:767–771PubMedCrossRef Petit T, Dommergues M, Socie G, Dumez Y, Gluckman E, Brison O (1997) Detection of maternal cells in human fetal blood during the third trimester of pregnancy using allele-specific PCR amplification. Br J Haematol 98:767–771PubMedCrossRef
26.
go back to reference Rustico MA, Benettoni A, Bussani R, Maieron A, Mandruzzato G (1995) Early fetal endocardial fibroelastosis and critical aortic stenosis: a case report. Ultrasound Obstet Gynecol 5:202–205PubMedCrossRef Rustico MA, Benettoni A, Bussani R, Maieron A, Mandruzzato G (1995) Early fetal endocardial fibroelastosis and critical aortic stenosis: a case report. Ultrasound Obstet Gynecol 5:202–205PubMedCrossRef
28.
go back to reference Sakaguchi S (2004) Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol 22:531–562PubMedCrossRef Sakaguchi S (2004) Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol 22:531–562PubMedCrossRef
29.
go back to reference Sardella G, De Luca L, Francavilla V, Accapezzato D, Mancone M, Sirinian MI, Fedele F, Paroli M (2007) Frequency of naturally occurring regulatory T cells is reduced in patients with ST-segment elevation myocardial infarction. Thromb Res 120:631–634PubMedCrossRef Sardella G, De Luca L, Francavilla V, Accapezzato D, Mancone M, Sirinian MI, Fedele F, Paroli M (2007) Frequency of naturally occurring regulatory T cells is reduced in patients with ST-segment elevation myocardial infarction. Thromb Res 120:631–634PubMedCrossRef
30.
go back to reference Sellers F, Keith J, Manning J (1964) The diagnosis of primary endocardial fibroelastosis. Circulation 29:49–59PubMed Sellers F, Keith J, Manning J (1964) The diagnosis of primary endocardial fibroelastosis. Circulation 29:49–59PubMed
31.
go back to reference Shearer WT, Pahwa S, Read JS, Chen J, Wijayawardana SR, Palumbo P, Abrams EJ, Nesheim SR, Yin W, Thompson B, Easley KA (2007) CD4/CD8 T-cell ratio predicts HIV infection in infants: the National Heart, Lung, and Blood Institute P2C2 Study. J Allergy Clin Immunol 120:1449–1456PubMedCrossRef Shearer WT, Pahwa S, Read JS, Chen J, Wijayawardana SR, Palumbo P, Abrams EJ, Nesheim SR, Yin W, Thompson B, Easley KA (2007) CD4/CD8 T-cell ratio predicts HIV infection in infants: the National Heart, Lung, and Blood Institute P2C2 Study. J Allergy Clin Immunol 120:1449–1456PubMedCrossRef
32.
go back to reference Shevach EM, Piccirillo CA, Thornton AM, McHugh RS (2003) Control of T cell activation by CD4+CD25+ suppressor T cells. Novartis Found Symp 252:24–36, discussion 36–44, 106–114 Shevach EM, Piccirillo CA, Thornton AM, McHugh RS (2003) Control of T cell activation by CD4+CD25+ suppressor T cells. Novartis Found Symp 252:24–36, discussion 36–44, 106–114
33.
go back to reference Takahashi T, Kuniyasu Y, Toda M, Sakaguchi N, Itoh M, Iwata M, Shimizu J, Sakaguchi S (1998) Immunologic self-tolerance maintained by CD25+CD4+ naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state. Int Immunol 10:1969–1980PubMedCrossRef Takahashi T, Kuniyasu Y, Toda M, Sakaguchi N, Itoh M, Iwata M, Shimizu J, Sakaguchi S (1998) Immunologic self-tolerance maintained by CD25+CD4+ naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state. Int Immunol 10:1969–1980PubMedCrossRef
34.
go back to reference Van der Geld H, Peetoom F, Somers K, Kanyerezi BR (1966) Immunohistological and serological studies in endomyocardial fibrosis. Lancet 2:1210–1213PubMedCrossRef Van der Geld H, Peetoom F, Somers K, Kanyerezi BR (1966) Immunohistological and serological studies in endomyocardial fibrosis. Lancet 2:1210–1213PubMedCrossRef
35.
go back to reference Weber R, Golding F, Jaeggi E (2008) Managing the fetus with atrioventricular block. Heart Rhythm 5:1347–1349PubMedCrossRef Weber R, Golding F, Jaeggi E (2008) Managing the fetus with atrioventricular block. Heart Rhythm 5:1347–1349PubMedCrossRef
36.
go back to reference Zandbergen HR, Sharma UC, Gupta S, Verjans JW, van den Borne S, Pokharel S, van Brakel T, Duijestijn A, van Rooijen N, Maessen JG, Reutelingsperger C, Pinto YM, Narula J, Hofstra L (2009) Macrophage depletion in hypertensive rats accelerates development of cardiomyopathy. J Cardiovasc Pharmacol Ther 14:68–75PubMedCrossRef Zandbergen HR, Sharma UC, Gupta S, Verjans JW, van den Borne S, Pokharel S, van Brakel T, Duijestijn A, van Rooijen N, Maessen JG, Reutelingsperger C, Pinto YM, Narula J, Hofstra L (2009) Macrophage depletion in hypertensive rats accelerates development of cardiomyopathy. J Cardiovasc Pharmacol Ther 14:68–75PubMedCrossRef
Metadata
Title
The Myocardium of Fetuses with Endocardial Fibroelastosis Contains Fewer B and T Lymphocytes than Normal Control Myocardium
Authors
Nisha M. Fernandes
Glenn P. Taylor
Cedric Manlhiot
Brian W. McCrindle
Michael Ho
Steven E. S. Miner
Adelle Atkinson
Edgar T. Jaeggi
Lynne E. Nield
Publication date
01-12-2011
Publisher
Springer-Verlag
Published in
Pediatric Cardiology / Issue 8/2011
Print ISSN: 0172-0643
Electronic ISSN: 1432-1971
DOI
https://doi.org/10.1007/s00246-011-9980-1

Other articles of this Issue 8/2011

Pediatric Cardiology 8/2011 Go to the issue