Skip to main content
Erschienen in: Journal of Clinical Immunology 2/2011

01.04.2011

CD8+ T Cells in Facioscapulohumeral Muscular Dystrophy Patients with Inflammatory Features at Muscle MRI

verfasst von: Giovanni Frisullo, Roberto Frusciante, Viviana Nociti, Giorgio Tasca, Rosaria Renna, Raffaele Iorio, Agata Katia Patanella, Elisabetta Iannaccone, Alessandro Marti, Monica Rossi, Assunta Bianco, Mauro Monforte, Pietro Attilio Tonali, Massimiliano Mirabella, Anna Paola Batocchi, Enzo Ricci

Erschienen in: Journal of Clinical Immunology | Ausgabe 2/2011

Einloggen, um Zugang zu erhalten

Abstract

Facioscapulohumeral muscular dystrophy (FSHD) is an inherited disease, and although strongly suggested, a contribution of inflammation to its pathogenesis has never been demonstrated. In FSHD patients, we found by immunohistochemistry inflammatory infiltrates mainly composed by CD8+ T cells in muscles showing hyperintensity features on T2-weighted short tau inversion recovery magnetic resonance imaging (T2-STIR-MRI) sequences. Therefore, we evaluated the presence of circulating activated immune cells and the production of cytokines in patients with or without muscles showing hyperintensity features on T2-STIR-MRI sequences and from controls. FSHD patients displaying hyperintensity features in one or more muscles showed higher CD8+pSTAT1+, CD8+T-bet+ T cells and CD14+pSTAT1+, CD14+T-bet+ cells percentages and IL12p40, IFNγ and TNFα levels than patients without muscles displaying hyperintense features and controls. Moreover, the percentages of CD8+pSTAT1+, CD8+T-bet+ and CD14+pSTAT1+ cells correlated with the proportion of muscles displaying hyperintensity features at T2-STIR sequences. These data indicate that circulating activated immune cells, mainly CD8+ T cells, may favour FSHD progression by promoting active phases of muscle inflammation.
Literatur
1.
Zurück zum Zitat Steinman L. Four easy pieces: interconnections between tissue injury, intermediary metabolism, autoimmunity, and chronic degeneration. Proc Am Thorac Soc. 2006;3:484–6.PubMedCrossRef Steinman L. Four easy pieces: interconnections between tissue injury, intermediary metabolism, autoimmunity, and chronic degeneration. Proc Am Thorac Soc. 2006;3:484–6.PubMedCrossRef
2.
Zurück zum Zitat Spencer MJ, Tidball JG. Do immune cells promote the pathology of dystrophin-deficient myopathies. Neuromuscul Disord. 2001;11:556–64.PubMedCrossRef Spencer MJ, Tidball JG. Do immune cells promote the pathology of dystrophin-deficient myopathies. Neuromuscul Disord. 2001;11:556–64.PubMedCrossRef
3.
Zurück zum Zitat Moser H, Dubye P, Fatemi A. Progress in X-linked adrenoleukodystrophy. Curr Opin Neurol. 2004;17:263–9.PubMedCrossRef Moser H, Dubye P, Fatemi A. Progress in X-linked adrenoleukodystrophy. Curr Opin Neurol. 2004;17:263–9.PubMedCrossRef
4.
Zurück zum Zitat Ranes J, Stoller K. Review of alpha 1-antitrypsin deficiency. Semin Respir Crit Care Med. 2005;26:154–66.PubMedCrossRef Ranes J, Stoller K. Review of alpha 1-antitrypsin deficiency. Semin Respir Crit Care Med. 2005;26:154–66.PubMedCrossRef
5.
Zurück zum Zitat Pescatori M, Broccolini A, Minetti C, Bertini E, Bruno C, D’amico A, et al. Gene expression profiling in the early phases of DMD: a constant molecular signature characterizes DMD muscle from early postnatal life throughout disease progression. FASEB J. 2007;21:1210–26.PubMedCrossRef Pescatori M, Broccolini A, Minetti C, Bertini E, Bruno C, D’amico A, et al. Gene expression profiling in the early phases of DMD: a constant molecular signature characterizes DMD muscle from early postnatal life throughout disease progression. FASEB J. 2007;21:1210–26.PubMedCrossRef
6.
Zurück zum Zitat Nagaraju K, Rawat R, Veszelovszky E, Thapliyal R, Kesari A, Sparks S, et al. Dysferlin deficiency enhances monocyte phagocytosis: a model for the inflammatory onset of limb-girdle muscular dystrophy 2B. Am J Pathol. 2008;172:774–85.PubMedCrossRef Nagaraju K, Rawat R, Veszelovszky E, Thapliyal R, Kesari A, Sparks S, et al. Dysferlin deficiency enhances monocyte phagocytosis: a model for the inflammatory onset of limb-girdle muscular dystrophy 2B. Am J Pathol. 2008;172:774–85.PubMedCrossRef
7.
Zurück zum Zitat van Deutekom JC, Wijmenga C, van Tienhoven EA, Gruter AM, Hewitt JE, Padberg GW, et al. FSHD associated DNA rearrangements are due to deletions of integral copies of a 3.2 kb tandemly repeated unit. Hum Mol Genet. 1993;2:2037–42.PubMedCrossRef van Deutekom JC, Wijmenga C, van Tienhoven EA, Gruter AM, Hewitt JE, Padberg GW, et al. FSHD associated DNA rearrangements are due to deletions of integral copies of a 3.2 kb tandemly repeated unit. Hum Mol Genet. 1993;2:2037–42.PubMedCrossRef
8.
Zurück zum Zitat Tawil R, Van Der Maarel SM. Facioscapulohumeral muscular dystrophy. Muscle Nerve. 2006;34:1–15.PubMedCrossRef Tawil R, Van Der Maarel SM. Facioscapulohumeral muscular dystrophy. Muscle Nerve. 2006;34:1–15.PubMedCrossRef
9.
Zurück zum Zitat Tupler R, Perini G, Pellegrino MA, Green MR. Profound misregulation of muscle-specific gene expression in facioscapulohumeral muscular dystrophy. Proc Natl Acad Sci USA. 1999;96:12650–4.PubMedCrossRef Tupler R, Perini G, Pellegrino MA, Green MR. Profound misregulation of muscle-specific gene expression in facioscapulohumeral muscular dystrophy. Proc Natl Acad Sci USA. 1999;96:12650–4.PubMedCrossRef
10.
Zurück zum Zitat Munsat TL, Piper D, Cancilla P, Mednick J. Inflammatory myopathy with facioscapulohumeral distribution. Neurology. 1972;22:335–47.PubMed Munsat TL, Piper D, Cancilla P, Mednick J. Inflammatory myopathy with facioscapulohumeral distribution. Neurology. 1972;22:335–47.PubMed
11.
Zurück zum Zitat Figarella-Branger D, Pellissier JF, Serratrice G, Pouget J, Bianco N. Immunocytochemical study of the inflammatory forms of facioscapulohumeral myopathies and correlation with other types of myositis. Ann Pathol. 1989;9:100–8.PubMed Figarella-Branger D, Pellissier JF, Serratrice G, Pouget J, Bianco N. Immunocytochemical study of the inflammatory forms of facioscapulohumeral myopathies and correlation with other types of myositis. Ann Pathol. 1989;9:100–8.PubMed
12.
Zurück zum Zitat Arahata K, Ishihara T, Fukunaga H, Orimo S, Lee JH, Goto K, et al. Inflammatory response in facioscapulohumeral muscular dystrophy (FSHD): immunocytochemical and genetic analyses. Muscle Nerve. 1995;2:S56–66.PubMedCrossRef Arahata K, Ishihara T, Fukunaga H, Orimo S, Lee JH, Goto K, et al. Inflammatory response in facioscapulohumeral muscular dystrophy (FSHD): immunocytochemical and genetic analyses. Muscle Nerve. 1995;2:S56–66.PubMedCrossRef
13.
Zurück zum Zitat Tawil R, McDermott MP, Pandya S, King W, Kissel J, Mendell JR, et al. A pilot trial of prednisone in facioscapulohumeral muscular dystrophy FSH-DY group. Neurology. 1997;48:46–9.PubMed Tawil R, McDermott MP, Pandya S, King W, Kissel J, Mendell JR, et al. A pilot trial of prednisone in facioscapulohumeral muscular dystrophy FSH-DY group. Neurology. 1997;48:46–9.PubMed
14.
Zurück zum Zitat Mercuri E, Talim B, Moghadaszadeh B, Petit N, Brockington M, Counsell S, et al. Clinical and imaging findings in six cases of congenital muscular dystrophy with rigid spine syndrome linked to chromosome 1p (RSMD1). Neuromuscul Disord. 2002;12:631–8.PubMedCrossRef Mercuri E, Talim B, Moghadaszadeh B, Petit N, Brockington M, Counsell S, et al. Clinical and imaging findings in six cases of congenital muscular dystrophy with rigid spine syndrome linked to chromosome 1p (RSMD1). Neuromuscul Disord. 2002;12:631–8.PubMedCrossRef
15.
Zurück zum Zitat Sookhoo S, Mackinnon I, Bushby K, Chinnery PF, Birchall D. MRI for the demonstration of subclinical muscle involvement in muscular dystrophy. Clin Radiol. 2007;62:160–5.PubMedCrossRef Sookhoo S, Mackinnon I, Bushby K, Chinnery PF, Birchall D. MRI for the demonstration of subclinical muscle involvement in muscular dystrophy. Clin Radiol. 2007;62:160–5.PubMedCrossRef
16.
Zurück zum Zitat Olsen DB, Gideon P, Jeppesen TD, Vissing J. Leg muscle involvement in facioscapulohumeral muscular dystrophy assessed by MRI. J Neurol. 2006;253:1437–41.PubMedCrossRef Olsen DB, Gideon P, Jeppesen TD, Vissing J. Leg muscle involvement in facioscapulohumeral muscular dystrophy assessed by MRI. J Neurol. 2006;253:1437–41.PubMedCrossRef
17.
Zurück zum Zitat Kan HE, Scheenen TW, Wohlgemuth M, Klomp DW, van Loosbroek-Wagenmans I, Padberg GW, et al. Quantitative MR imaging of individual muscle involvement in facioscapulohumeral muscular dystrophy. Neuromuscul Disord. 2009;19:357–62.PubMedCrossRef Kan HE, Scheenen TW, Wohlgemuth M, Klomp DW, van Loosbroek-Wagenmans I, Padberg GW, et al. Quantitative MR imaging of individual muscle involvement in facioscapulohumeral muscular dystrophy. Neuromuscul Disord. 2009;19:357–62.PubMedCrossRef
18.
Zurück zum Zitat May DA, Disler DG, Jones EA, Balkissoon AA, Manaster BJ. Abnormal signal intensity in skeletal muscle at MR imaging: patterns, pearls, and pitfalls. Radiographics. 2000;20:S295–315.PubMed May DA, Disler DG, Jones EA, Balkissoon AA, Manaster BJ. Abnormal signal intensity in skeletal muscle at MR imaging: patterns, pearls, and pitfalls. Radiographics. 2000;20:S295–315.PubMed
19.
Zurück zum Zitat Kamath S, Venkatanarasimha N, Walsh MA, Hughes PM. MRI appearance of muscle denervation. Skeletal Radiol. 2008;37:397–404.PubMedCrossRef Kamath S, Venkatanarasimha N, Walsh MA, Hughes PM. MRI appearance of muscle denervation. Skeletal Radiol. 2008;37:397–404.PubMedCrossRef
20.
Zurück zum Zitat Ricci E, Galluzzi G, Deidda G, Cacurri S, Colantoni L, Merico B, et al. Progress in the molecular diagnosis of facioscapulohumeral muscular dystrophy and correlation between the number of KpnI repeats at the 4q35 locus and clinical phenotype. Ann Neurol. 1999;45:751–7.PubMedCrossRef Ricci E, Galluzzi G, Deidda G, Cacurri S, Colantoni L, Merico B, et al. Progress in the molecular diagnosis of facioscapulohumeral muscular dystrophy and correlation between the number of KpnI repeats at the 4q35 locus and clinical phenotype. Ann Neurol. 1999;45:751–7.PubMedCrossRef
21.
Zurück zum Zitat Lynöe N, Sandlund M, Dahlqvist G, Jacobsson L. Informed consent: study of quality of information given to participants in a clinical trial. BMJ. 1991;303:610–3.PubMedCrossRef Lynöe N, Sandlund M, Dahlqvist G, Jacobsson L. Informed consent: study of quality of information given to participants in a clinical trial. BMJ. 1991;303:610–3.PubMedCrossRef
22.
Zurück zum Zitat Brunn A, Schroder R, Deckert M. The inflammatory reaction pattern distinguishes primary dysferlinopathies from idiopathic inflammatory myopathies: an important role for the membrane attack complex. Acta Neuropathol. 2006;112:325–32.PubMedCrossRef Brunn A, Schroder R, Deckert M. The inflammatory reaction pattern distinguishes primary dysferlinopathies from idiopathic inflammatory myopathies: an important role for the membrane attack complex. Acta Neuropathol. 2006;112:325–32.PubMedCrossRef
23.
Zurück zum Zitat Wang J, Fathman JW, Lugo-Villarino G, Scimone L, von Andrian U, Dorfman DM, et al. Transcription factor T-bet regulates inflammatory arthritis through its function in dendritic cells. J Clin Invest. 2006;116:414–21.PubMedCrossRef Wang J, Fathman JW, Lugo-Villarino G, Scimone L, von Andrian U, Dorfman DM, et al. Transcription factor T-bet regulates inflammatory arthritis through its function in dendritic cells. J Clin Invest. 2006;116:414–21.PubMedCrossRef
24.
Zurück zum Zitat Lighvani AA, Frucht DM, Jankovic D, Yamane H, Aliberti J, Hissong BD, et al. T-bet is rapidly induced by interferon-gamma in lymphoid and myeloid cells. Proc Natl Acad Sci USA. 2001;98:15137–42.PubMedCrossRef Lighvani AA, Frucht DM, Jankovic D, Yamane H, Aliberti J, Hissong BD, et al. T-bet is rapidly induced by interferon-gamma in lymphoid and myeloid cells. Proc Natl Acad Sci USA. 2001;98:15137–42.PubMedCrossRef
25.
Zurück zum Zitat Afkarian M, Sedy JR, Yang J, Jacobson NG, Cereb N, Yang SY, et al. T-bet is a STAT1-induced regulator of IL-12R receptor in naïve CD4+ cells. Nat Immunol. 2002;3:549–57.PubMedCrossRef Afkarian M, Sedy JR, Yang J, Jacobson NG, Cereb N, Yang SY, et al. T-bet is a STAT1-induced regulator of IL-12R receptor in naïve CD4+ cells. Nat Immunol. 2002;3:549–57.PubMedCrossRef
26.
Zurück zum Zitat Mullen AC, High FA, Hutchins AS, Lee HW, Villarino AV, Livingston DM, et al. Role of T-bet in commitment of TH1 cells before IL-12-dependent selection. Science. 2001;292:1907–10.PubMedCrossRef Mullen AC, High FA, Hutchins AS, Lee HW, Villarino AV, Livingston DM, et al. Role of T-bet in commitment of TH1 cells before IL-12-dependent selection. Science. 2001;292:1907–10.PubMedCrossRef
27.
Zurück zum Zitat Yang Y, Ochando JC, Bromberg JS, Ding Y. Identification of a distant T-bet enhancer responsive to IL-12/Stat4 and IFNgamma/Stat1 signals. Blood. 2007;110:2494–500.PubMedCrossRef Yang Y, Ochando JC, Bromberg JS, Ding Y. Identification of a distant T-bet enhancer responsive to IL-12/Stat4 and IFNgamma/Stat1 signals. Blood. 2007;110:2494–500.PubMedCrossRef
28.
Zurück zum Zitat Mayer KD, Mohrs K, Reiley W, Wittmer S, Kohlmeier JE, Pearl JE, et al. Cutting edge: T-bet and IL-27R are critical for in vivo IFN-gamma production by CD8 T cells during infection. J Immunol. 2008;180:693–7.PubMed Mayer KD, Mohrs K, Reiley W, Wittmer S, Kohlmeier JE, Pearl JE, et al. Cutting edge: T-bet and IL-27R are critical for in vivo IFN-gamma production by CD8 T cells during infection. J Immunol. 2008;180:693–7.PubMed
29.
Zurück zum Zitat Sullivan BM, Juedes A, Szabo SJ, von Herrath M, Glimcher LH. Antigen-driven effector CD8 T cell function regulated by T-bet. Proc Natl Acad Sci USA. 2003;100:15818–23.PubMedCrossRef Sullivan BM, Juedes A, Szabo SJ, von Herrath M, Glimcher LH. Antigen-driven effector CD8 T cell function regulated by T-bet. Proc Natl Acad Sci USA. 2003;100:15818–23.PubMedCrossRef
30.
Zurück zum Zitat Cruz-Guilloty F, Pipkin ME, Djuretic IM, Levanon D, Lotem J, Lichtenheld MG, et al. Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs. J Exp Med. 2009;206:51–9.PubMedCrossRef Cruz-Guilloty F, Pipkin ME, Djuretic IM, Levanon D, Lotem J, Lichtenheld MG, et al. Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs. J Exp Med. 2009;206:51–9.PubMedCrossRef
31.
Zurück zum Zitat Manel N, Unutmaz D, Littman DR. The differentiation of human T(H)-17 cells requires transforming growth factor-beta and induction of the nuclear receptor RORgammat. Nat Immunol. 2008;9:641–9.PubMedCrossRef Manel N, Unutmaz D, Littman DR. The differentiation of human T(H)-17 cells requires transforming growth factor-beta and induction of the nuclear receptor RORgammat. Nat Immunol. 2008;9:641–9.PubMedCrossRef
32.
Zurück zum Zitat Takeda K, Kaisho T, Yoshida N, Takeda J, Kishimoto T, Akira S. Stat3 activation is responsible for IL-6-dependent T cell proliferation through preventing apoptosis: generation and characterization of T cell-specific Stat3-deficient mice. J Immunol. 1998;161(9):4652–60.PubMed Takeda K, Kaisho T, Yoshida N, Takeda J, Kishimoto T, Akira S. Stat3 activation is responsible for IL-6-dependent T cell proliferation through preventing apoptosis: generation and characterization of T cell-specific Stat3-deficient mice. J Immunol. 1998;161(9):4652–60.PubMed
33.
Zurück zum Zitat Mangan JK, Rane SG, Kang AD, Amanullah A, Wong BC, Reddy EP. Mechanisms associated with IL-6-induced up-regulation of Jak3 and its role in monocytic differentiation. Blood. 2004;103:4093–101.PubMedCrossRef Mangan JK, Rane SG, Kang AD, Amanullah A, Wong BC, Reddy EP. Mechanisms associated with IL-6-induced up-regulation of Jak3 and its role in monocytic differentiation. Blood. 2004;103:4093–101.PubMedCrossRef
34.
Zurück zum Zitat Volpe E, Servant N, Zollinger R, Bogiatzi SI, Hupé P, Barillot E, et al. A critical function for transforming growth factor-beta, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 responses. Nat Immunol. 2008;9:650–7.PubMedCrossRef Volpe E, Servant N, Zollinger R, Bogiatzi SI, Hupé P, Barillot E, et al. A critical function for transforming growth factor-beta, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 responses. Nat Immunol. 2008;9:650–7.PubMedCrossRef
35.
Zurück zum Zitat O’Garra A, Vieira P. T(H)1 cells control themselves by producing interleukin-10. Nat Rev Immunol. 2007;7:425–8.PubMedCrossRef O’Garra A, Vieira P. T(H)1 cells control themselves by producing interleukin-10. Nat Rev Immunol. 2007;7:425–8.PubMedCrossRef
36.
Zurück zum Zitat Corinti S, Albanesi C, la Sala A, Pastore S, Girolomoni G. Regulatory activity of autocrine IL-10 on dendritic cell functions. J Immunol. 2001;166:4312–8.PubMed Corinti S, Albanesi C, la Sala A, Pastore S, Girolomoni G. Regulatory activity of autocrine IL-10 on dendritic cell functions. J Immunol. 2001;166:4312–8.PubMed
37.
Zurück zum Zitat Hoentjen F, Sartor RB, Ozaki M, Jobin C. STAT3 regulates NF-kappaB recruitment to the IL-12p40 promoter in dendritic cells. Blood. 2005;105:689–96.PubMedCrossRef Hoentjen F, Sartor RB, Ozaki M, Jobin C. STAT3 regulates NF-kappaB recruitment to the IL-12p40 promoter in dendritic cells. Blood. 2005;105:689–96.PubMedCrossRef
38.
Zurück zum Zitat Williams L, Bradley L, Smith A, Foxwell B. Signal transducer and activator of transcription 3 is the dominant mediator of the anti-inflammatory effects of IL-10 in human macrophages. J Immunol. 2004;172:567–76.PubMed Williams L, Bradley L, Smith A, Foxwell B. Signal transducer and activator of transcription 3 is the dominant mediator of the anti-inflammatory effects of IL-10 in human macrophages. J Immunol. 2004;172:567–76.PubMed
39.
Zurück zum Zitat Murray PJ. Understanding and exploiting the endogenous interleukin-10/STAT3-mediated anti-inflammatory response. Curr Opin Pharmacol. 2006;6:379–86.PubMedCrossRef Murray PJ. Understanding and exploiting the endogenous interleukin-10/STAT3-mediated anti-inflammatory response. Curr Opin Pharmacol. 2006;6:379–86.PubMedCrossRef
40.
Zurück zum Zitat Stumhofer JS, Silver JS, Laurence A, Porrett PM, Harris TH, Turka LA, et al. Interleukins 27 and 6 induce STAT3-mediated T cell production of interleukin 10. Nat Immunol. 2007;8:1363–71.PubMedCrossRef Stumhofer JS, Silver JS, Laurence A, Porrett PM, Harris TH, Turka LA, et al. Interleukins 27 and 6 induce STAT3-mediated T cell production of interleukin 10. Nat Immunol. 2007;8:1363–71.PubMedCrossRef
41.
Zurück zum Zitat Janssen SP, Gayan-Ramirez G, Van den Bergh A, Herijgers P, Maes K, Verbeken E, et al. Interleukin-6 causes myocardial failure and skeletal muscle atrophy in rats. Circulation. 2005;111:996–1005.PubMedCrossRef Janssen SP, Gayan-Ramirez G, Van den Bergh A, Herijgers P, Maes K, Verbeken E, et al. Interleukin-6 causes myocardial failure and skeletal muscle atrophy in rats. Circulation. 2005;111:996–1005.PubMedCrossRef
42.
Zurück zum Zitat Haddad F, Zaldivar F, Cooper DM, Adams GR. IL-6-induced skeletal muscle atrophy. J Appl Physiol. 2005;98:911–7.PubMedCrossRef Haddad F, Zaldivar F, Cooper DM, Adams GR. IL-6-induced skeletal muscle atrophy. J Appl Physiol. 2005;98:911–7.PubMedCrossRef
43.
Zurück zum Zitat Schaap LA, Pluijm SM, Deeg DJ, Visser M. Inflammatory markers and loss of muscle mass (sarcopenia) and strength. Am J Med. 2006;119:9–17.CrossRef Schaap LA, Pluijm SM, Deeg DJ, Visser M. Inflammatory markers and loss of muscle mass (sarcopenia) and strength. Am J Med. 2006;119:9–17.CrossRef
44.
Zurück zum Zitat Toth MJ, Ades PA, Tischler MD, Tracy RP, LeWinter MM. Immune activation is associated with reduced skeletal muscle mass and physical function in chronic heart failure. Int J Cardiol. 2006;109:179–87.PubMedCrossRef Toth MJ, Ades PA, Tischler MD, Tracy RP, LeWinter MM. Immune activation is associated with reduced skeletal muscle mass and physical function in chronic heart failure. Int J Cardiol. 2006;109:179–87.PubMedCrossRef
45.
Zurück zum Zitat Huey KA, McCusker RH, Kelley KW. Exaggerated expression of skeletal muscle-derived interleukin-6, but not TNFalpha, in mice lacking interleukin-10. J Neuroimmunol. 2008;199:56–62.PubMedCrossRef Huey KA, McCusker RH, Kelley KW. Exaggerated expression of skeletal muscle-derived interleukin-6, but not TNFalpha, in mice lacking interleukin-10. J Neuroimmunol. 2008;199:56–62.PubMedCrossRef
Metadaten
Titel
CD8+ T Cells in Facioscapulohumeral Muscular Dystrophy Patients with Inflammatory Features at Muscle MRI
verfasst von
Giovanni Frisullo
Roberto Frusciante
Viviana Nociti
Giorgio Tasca
Rosaria Renna
Raffaele Iorio
Agata Katia Patanella
Elisabetta Iannaccone
Alessandro Marti
Monica Rossi
Assunta Bianco
Mauro Monforte
Pietro Attilio Tonali
Massimiliano Mirabella
Anna Paola Batocchi
Enzo Ricci
Publikationsdatum
01.04.2011
Verlag
Springer US
Erschienen in
Journal of Clinical Immunology / Ausgabe 2/2011
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-010-9474-6

Weitere Artikel der Ausgabe 2/2011

Journal of Clinical Immunology 2/2011 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.