Sarcoidosis: Are There Sarcoidosis Genes?

  • Helmut H. Popper
Part of the Molecular Pathology Library book series (MPLB, volume 1)


More than 100 years have passed since the first description of sarcoidosis by Hutchinson1 and the identification of sarcoid granulomas by Besnier,2 Boeck,3 and Schaumann,4 but the causative agent or agents of sarcoidosis still have not been identified. However, in these intervening years, considerable knowledge has accumulated about the pathogenesis and the molecular events that lead to the granulomatous reaction. Clinical evaluation has shed some light on this systemic disease; pathology and immunology have contributed to our understanding of the inflammatory process. More recently, genetics and molecular biology have opened new avenues of research for this still enigmatic disease. There is some hope that new techniques provided by molecular biology, employing samples from bronchoalveolar lavage and biopsies, might elucidate the causative agents behind this disease and define the genetic modifications that make some people prone to developing sarcoidosis.


Human Leukocyte Antigen Respir Crit Human Leukocyte Antigen Class Cardiac Sarcoidosis Sarcoidosis Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Hutchinson J. Mortimer’s malady: a form of lupus pernio. Arch Surg 1898;9:307–315.Google Scholar
  2. 2.
    Besnier E. Lupus pernio de la face. Ann Dermatol Syphiligr 1889;10:33–36.Google Scholar
  3. 3.
    Boeck C. Multiple benign sarcoid of the skin. Norsk Mag Laegevid 1899;14:1321–1345.Google Scholar
  4. 4.
    Schaumann J. Lymphogranuloma benigna in the light of prolonged clinical observations and autopsy findings. Br J Dermatol 1936;48:346–399.CrossRefGoogle Scholar
  5. 5.
    Löfgren S. Primary pulmonary sarcoidosis. I Early signs and symptoms. Acta Med Scand 1953;145:424–431.PubMedGoogle Scholar
  6. 6.
    Romer FK. Sarcoidosis with large nodular lesions simulating pulmonary metastases. An analysis of 126 cases of intrathoracic sarcoidosis. Scand J Respir Dis 1977;58:11–16.PubMedGoogle Scholar
  7. 7.
    Churg A. Pulmonary angiitis and granulomatosis revisited. Hum Pathol 1983;14:868–883.CrossRefPubMedGoogle Scholar
  8. 8.
    Liebow AA. The J. Burns Amberson lecture—pulmonary angiitis and granulomatosis. Am Rev Respir Dis 1973;108:1–18.PubMedGoogle Scholar
  9. 9.
    Churg A, Carrington CB, Gupta R. Necrotizing sarcoid granulomatosis. Chest 1979;76:406–413.CrossRefPubMedGoogle Scholar
  10. 10.
    Popper HH KH, Churg A, Colby TV. Necrotizing sarcoid granulomatosis—is it different from nodular sarcoidosis? Pneumology 2003;57:268–271.CrossRefGoogle Scholar
  11. 11.
    Ishioka S, Saito T, Hiyama K, et al. Increased expression of tumor necrosis factor-alpha, interleukin-6, platelet-derived growth factor-B and granulocyte-macrophage colonystimulating factor mRNA in cells of bronchoalveolar lavage fluids from patients with sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 1996;13:139–145.PubMedGoogle Scholar
  12. 12.
    Llombart A, Jr., Escudero JM. The incidence and significance of epithelioid and sarcoid-like cellular reaction in the stromata of malignant tumours. A morphological and experimental study. Eur J Cancer 1970;6:545–551.PubMedGoogle Scholar
  13. 13.
    Bassler R, Birke F. Histopathology of tumour associated sarcoid-like stromal reaction in breast cancer. An analysis of 5 cases with immunohistochemical investigations. Virchows Arch A Pathol Anat Histopathol 1988;412:231–239.CrossRefPubMedGoogle Scholar
  14. 14.
    Parra ER, Canzian M, Saber AM, et al. Pulmonary and mediastinal “sarcoidosis” following surgical resection of cancer. Pathol Res Pract 2004;200:701–705CrossRefPubMedGoogle Scholar
  15. 15.
    Amicosante M, Fontenot AP. T cell recognition in chronic beryllium disease. Clin Immunol 2006;121(2):134–143.CrossRefPubMedGoogle Scholar
  16. 16.
    Bill JR, Mack DG, Falta MT, et al. Beryllium presentation to CD4+ T cells is dependent on a single amino acid residue of the MHC class II beta-chain, J Immunol 2005;175:7029–7037.PubMedGoogle Scholar
  17. 17.
    Saltini C, Amicosante M. Beryllium disease. Am J Med Sci 2001;321:89–98CrossRefPubMedGoogle Scholar
  18. 18.
    Fontenot AP, Torres M, Marshall WH, et al. Beryllium presentation to CD4+ T cells underlies disease-susceptibility HLA-DP alleles in chronic beryllium disease. Proc Natl Acad Sci USA 2000;97:12717–12722.CrossRefPubMedGoogle Scholar
  19. 19.
    Gaede KI, Amicosante M, Schurmann M, et al. Function associated transforming growth factor-beta gene polymorphism in chronic beryllium disease. J Mol Med 2005;83:397–405.CrossRefPubMedGoogle Scholar
  20. 20.
    Shigehara K, Shijubo N, Ohmichi M, et al. Enhanced mRNA expression of Th1 cytokines and IL-12 in active pulmonary sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2000;17:151–157.PubMedGoogle Scholar
  21. 21.
    Cameron LA, Taha RA, Tsicopoulos A, et al. Airway epithelium expresses interleukin-18. Eur Respir J 1999;14:553–559.CrossRefPubMedGoogle Scholar
  22. 22.
    Lucas S, Ghilardi N, Li J, et al. IL-27 regulates IL-12 responsiveness of naive CD4+ T cells through Stat1-dependent and-independent mechanisms. Proc Natl Acad Sci USA 2003;100:15047–15052.CrossRefPubMedGoogle Scholar
  23. 23.
    Negishi T, Kato Y, Ooneda O, et al. Effects of aryl hydrocarbon receptor signaling on the modulation of TH1/TH2 balance. J Immunol 2005;175:7348–7356.PubMedGoogle Scholar
  24. 24.
    Salmond RJ, Huyer G, Kotsoni A, et al. The src homology 2 domain-containing tyrosine phosphatase 2 regulates primary T-dependent immune responses and Th cell differentiation. J Immunol 2005;175:6498–6508.PubMedGoogle Scholar
  25. 25.
    Yamashita M, Shinnakasu R, Asou H, et al. Ras-ERK MAPK cascade regulates GATA3 stability and Th2 differentiation through ubiquitin-proteasome pathway. J Biol Chem 2005;280:29409–29419.CrossRefPubMedGoogle Scholar
  26. 26.
    Ziegenhagen MW, Benner UK, Zissel G, et al. Sarcoidosis: TNF-alpha release from alveolar macrophages and serum level of sIL-2R are prognostic markers. Am J Respir Crit Care Med 1997;156:1586–1592.PubMedGoogle Scholar
  27. 27.
    Kunkel SL, Lukacs NW, Strieter RM, et al. Th1 and Th2 responses regulate experimental lung granuloma development. Sarcoidosis Vasc Diffuse Lung Dis 1996;13:120–128.PubMedGoogle Scholar
  28. 28.
    Graham DY MD, Kalter DC, Yoshimura HH. Isolation of cell wall defective acid fast bacteria from skin lesions in patients with sarcoidosis. In Grassi C, Rizzato G, Pozzi E, eds. Sarcoidosis and Other Granulomatous Disorders. 1988:161–164.Google Scholar
  29. 29.
    Ikonomopoulos JA, Gorgoulis VG, Kastrinakis NG, et al. Experimental inoculation of laboratory animals with samples collected from sarcoidal patients and molecular diagnostic evaluation of the results. In Vivo 2000;14:761–765.PubMedGoogle Scholar
  30. 30.
    Milman N, Lisby G, Friis S, et al. Prolonged culture for mycobacteria in mediastinal lymph nodes from patients with pulmonary sarcoidosis. A negative study. Sarcoidosis Vasc Diffuse Lung Dis 2004;21:25–28.PubMedGoogle Scholar
  31. 31.
    el-Zaatari FA, Naser SA, Markesich DC, et al. Identification of Mycobacterium avium complex in sarcoidosis. J Clin Microbiol 1996;34:2240–2245.PubMedGoogle Scholar
  32. 32.
    Fidler H, Rook GA, Johnson NM, et al. Search for mycobacterial DNA in granulomatous tissues from patients with sarcoidosis using the polymerase chain reaction. Am Rev Respir Dis 1993;147:777–778.PubMedGoogle Scholar
  33. 33.
    Gudit VS, Campbell SM, Gould D, et al. Activation of cutaneous sarcoidosis following Mycobacterium marinum infection of skin. J Eur Acad Dermatol Venereol 2000;14:296–297.CrossRefPubMedGoogle Scholar
  34. 34.
    Mitchell IC, Turk JL, Mitchell DN. Detection of mycobacterial rRNA in sarcoidosis with liquid-phase hybridisation. Lancet 1992;339:1015–1017.CrossRefPubMedGoogle Scholar
  35. 35.
    Popper HH, Klemen H, Hoefler G, et al. Presence of mycobacterial DNA in sarcoidosis. Hum Pathol 1997;28:796–800.CrossRefPubMedGoogle Scholar
  36. 36.
    Klemen H, Husain AN, Cagle PT, et al. Mycobacterial DNA in recurrent sarcoidosis in the transplanted lung—a PCR-based study on four cases. Virchows Arch 2000;436:365–369.CrossRefPubMedGoogle Scholar
  37. 37.
    Saboor SA, Johnson NM, McFadden J. Detection of mycobacterial DNA in sarcoidosis and tuberculosis with polymerase chain reaction. Lancet 1992;339:1012–1015.CrossRefPubMedGoogle Scholar
  38. 38.
    Ghossein RA, Ross DG, Salomon RN, et al. A search for mycobacterial DNA in sarcoidosis using the polymerase chain reaction. Am J Clin Pathol 1994;101:733–737.PubMedGoogle Scholar
  39. 39.
    Richter E, Greinert U, Kirsten D, et al. Assessment of mycobacterial DNA in cells and tissues of mycobacterial and sarcoid lesions. Am J Respir Crit Care Med 1996;153:375–380.PubMedGoogle Scholar
  40. 40.
    Vokurka M, Lecossier D, du Bois RM, et al. Absence of DNA from mycobacteria of the M. tuberculosis complex in sarcoidosis. Am J Respir Crit Care Med 1997;156:1000–1003.PubMedGoogle Scholar
  41. 41.
    Alavi HA, Moscovic EA. Immunolocalization of cell-walldeficient forms of Mycobacterium tuberculosis complex in sarcoidosis and in sinus histiocytosis of lymph nodes draining carcinoma. Histol Histopathol 1996;11:683–694.PubMedGoogle Scholar
  42. 42.
    Graham DY, Markesich DC, Kalter DC, et al. Mycobacterial aetiology of sarcoidosis. Lancet 1992;340:52–53.CrossRefPubMedGoogle Scholar
  43. 43.
    Popper HH, Klemen H, Hoefler G, et al. Presence of mycobacterial DNA in sarcoidosis. Hum Pathol 1997;28:796–800.CrossRefPubMedGoogle Scholar
  44. 44.
    Ragno S CM, Lowrie DB, Winrow VR, et al. Protection of rats from adjuvant arthritis by immunization with naked DNA encoding for mycobacterial heat shock protein 65. Arthritis Rheum 1997;40:277–283.CrossRefPubMedGoogle Scholar
  45. 45.
    Huygen K CJ, Denis O, Montgomery DL, et al. Immunogenicity and protective efficacy of a tuberculosis DNA vaccine. Nat Med 1996;2:893–898.CrossRefPubMedGoogle Scholar
  46. 46.
    Thonhofer R, Maercker C, Popper HH. Expression of sarcoidosis related genes in lung lavage cells. Sarcoidosis Vasc Diffuse Lung Dis 2002;19:59–65.PubMedGoogle Scholar
  47. 47.
    Vabulas RM, Ahmad-Nejad P, da Costa C, et al. Endocytosed HSP60s use toll-like receptor 2 (TLR2) and TLR4 to activate the toll/interleukin-1 receptor signaling pathway in innate immune cells. J Biol Chem 2001;276:31332–31339.CrossRefPubMedGoogle Scholar
  48. 48.
    Kirschning CJ, Schumann RR. TLR2: cellular sensor for microbial and endogenous molecular patterns. Curr Top Microbiol Immunol 2002;270:121–144.PubMedGoogle Scholar
  49. 49.
    Rha YH, Taube C, Haczku A, et al. Effect of microbial heat shock proteins on airway inflammation and hyperresponsiveness. J Immunol 2002;169:5300–5307.PubMedGoogle Scholar
  50. 50.
    Petzmann SCM, Markert E, Kern I, et al. Enhanced proliferation and decreased apoptosis in lung lavage cells of sarcoidosis patients. Sarcoidosis Vasc Diffuse Lung Dis 2007 (in press.)Google Scholar
  51. 51.
    Ishige I, Usui Y, Takemura T, et al. Quantitative PCR of mycobacterial and propionibacterial DNA in lymph nodes of Japanese patients with sarcoidosis. Lancet 1999;354:120–123.CrossRefPubMedGoogle Scholar
  52. 52.
    McCaskill JG, Chason KD, Hua X, et al. Pulmonary immune responses to Propionibacterium acnes in C57BL/6 and BALB/c mice. Am J Respir Cell Mol Biol 2006;35(3):347–356.CrossRefPubMedGoogle Scholar
  53. 53.
    Minami J, Eishi Y, Ishige Y, et al. Pulmonary granulomas caused experimentally in mice by a recombinant triggerfactor protein of Propionibacterium acnes. J Med Dent Sci 2003;50:265–274.PubMedGoogle Scholar
  54. 54.
    Costabel U, Hunninghake GW. ATS/ERS/WASOG statement on sarcoidosis. Sarcoidosis Statement Committee. American Thoracic Society. European Respiratory Society. World Association for Sarcoidosis and Other Granulomatous Disorders. Eur Respir J 1999;14:735–737.CrossRefPubMedGoogle Scholar
  55. 55.
    McGrath DS, Goh N, Foley PJ, et al. Sarcoidosis: genes and microbes—soil or seed? Sarcoidosis Vasc Diffuse Lung Dis 2001;18:149–164.PubMedGoogle Scholar
  56. 56.
    Iannuzzi MC, Maliarik MJ, Poisson LM, et al. Sarcoidosis susceptibility and resistance HLA-DQB1 alleles in African Americans. Am J Respir Crit Care Med 2003;167:1225–1231.CrossRefPubMedGoogle Scholar
  57. 57.
    Voorter CE, Drent M, van den Berg-Loonen EM. Severe pulmonary sarcoidosis is strongly associated with the haplotype HLA-DQB1*0602-DRB1*150101. Hum Immunol 2005;66:826–835.CrossRefPubMedGoogle Scholar
  58. 58.
    Kruit A, Grutters JC, Ruven HJ, et al. Transforming growth factor-beta gene polymorphisms in sarcoidosis patients with and without fibrosis. Chest 2006;129:1584–1591.CrossRefPubMedGoogle Scholar
  59. 59.
    Hill MR, Papafili A, Booth H, et al. Functional prostaglandin-endoperoxide synthase 2 polymorphism predicts poor outcome in sarcoidosis. Am J Respir Crit Care Med 2006;174(8):915–922.CrossRefPubMedGoogle Scholar
  60. 60.
    Spagnolo P, Renzoni EA, Wells AU, et al. C-C chemokine receptor 2 and sarcoidosis: association with Lofgren’s syndrome. Am J Respir Crit Care Med 2003;168:1162–1166.CrossRefPubMedGoogle Scholar
  61. 61.
    Bogunia-Kubik K, Koscinska K, Suchnicki K, et al. HSP70-hom gene single nucleotide (+2763 G/A and +2437 C/T) polymorphisms in sarcoidosis. Int J Immunogenet 2006;33:135–140.CrossRefPubMedGoogle Scholar
  62. 62.
    Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol 2004;4:499–511.CrossRefPubMedGoogle Scholar
  63. 63.
    Leung TF, Tang NL, Wong GW, et al. CD 14 and toll-like receptors: potential contribution of genetic factors and mechanisms to inflammation and allergy, Curr Drug Targets Inflamm Allergy 2005;4:169–175.CrossRefPubMedGoogle Scholar
  64. 64.
    Vabulas RM, Ahmad-Nejad P, Ghose S, et al. HSP70 as endogenous stimulus of the Toll/interleukin-1 receptor signal pathway. J Biol Chem 2002;277:15107–15112.CrossRefPubMedGoogle Scholar
  65. 65.
    Jones RG, Elford AR, Parsons MJ, et al. CD28-dependent activation of protein kinase B/Akt blocks Fas-mediated apoptosis by preventing death-inducing signaling complex assembly. J Exp Med 2002;196:335–348.CrossRefPubMedGoogle Scholar
  66. 66.
    Parry RV, Rumbley CA, Vandenberghe LH, et al. CD28 and inducible costimulatory protein Src homology 2 binding domains show distinct regulation of phosphatidylinositol 3-kinase, Bcl-xL, and IL-2 expression in primary human CD4 T lymphocytes. J Immunol 2003;171:166–174.PubMedGoogle Scholar
  67. 67.
    Beutler B. Inferences, questions and possibilities in Tolllike receptor signalling. Nature 2004;430:257–263.CrossRefPubMedGoogle Scholar
  68. 68.
    Pabst S, Baumgarten G, Stremmel A, et al. Toll-like receptor (TLR) 4 polymorphisms are associated with a chronic course of sarcoidosis. Clin Exp Immunol 2006;143:420–426.CrossRefPubMedGoogle Scholar
  69. 69.
    Fukao T, Koyasu S. PI3K and negative regulation of TLR signaling. Trends Immunol 2003;24:358–363.CrossRefPubMedGoogle Scholar
  70. 70.
    Valentonyte R, Hampe J, Huse K, et al. Sarcoidosis is associated with a truncating splice site mutation in BTNL2. Nat Genet 2005;37:357–364.CrossRefPubMedGoogle Scholar
  71. 71.
    Rybicki BA, Walewski JL, Maliarik MJ, et al. The BTNL2 gene and sarcoidosis susceptibility in African Americans and Whites. Am J Hum Genet 2005;77:491–499.CrossRefPubMedGoogle Scholar
  72. 72.
    Nguyen T, Liu XK, Zhang Y, et al. BTNL2, a butyrophilin-like molecule that functions to inhibit T cell activation. J Immunol 2006;176:7354–7360.PubMedGoogle Scholar
  73. 73.
    Martinetti M, Tinelli C, Kolek V, et al. “The sarcoidosis map”: a joint survey of clinical and immunogenetic findings in two European countries. Am J Respir Crit Care Med 1995;152:557–564PubMedGoogle Scholar
  74. 74.
    Grunewald J, Eklund A, Olerup O. Human leukocyte antigen class I alleles and the disease course in sarcoidosis patients. Am J Respir Crit Care Med 2004;169:696–702.CrossRefPubMedGoogle Scholar
  75. 75.
    Schürmann M, Lympany PA, Reichel P, et al. Familial sarcoidosis is linked to the major histocompatibility complex region. Am J Respir Crit Care Med 2000;162:861–864.PubMedGoogle Scholar
  76. 76.
    Schurmann M, Reichel P, Muller-Myhsok B, et al. Results from a genome-wide search for predisposing genes in sarcoidosis. Am J Respir Crit Care Med 2001;164:840–846.PubMedGoogle Scholar
  77. 77.
    Valentonyte R, Hampe J, Croucher PJ, et al. Study of C-C chemokine receptor 2 alleles in sarcoidosis, with emphasis on family-based analysis. Am J Respir Crit Care Med 2005;171:1136–1141.CrossRefPubMedGoogle Scholar
  78. 78.
    Rossman MD, Thompson B, Frederick M, et al. HLADRB1* 1101: a significant risk factor for sarcoidosis in blacks and whites. Am J Hum Genet 2003;73:720–735.CrossRefPubMedGoogle Scholar
  79. 79.
    Sato H, Grutters JC, Pantelidis P, et al. HLA-DQB1*0201: a marker for good prognosis in British and Dutch patients with sarcoidosis. Am J Respir Cell Mol Biol 2002;27:406–412.PubMedGoogle Scholar
  80. 80.
    Foley PJ, McGrath DS, Puscinska E, et al. Human leukocyte antigen-DRB1 position 11 residues are a common protective marker for sarcoidosis. Am J Respir Cell Mol Biol 2001;25:272–277.PubMedGoogle Scholar
  81. 81.
    Seitzer U, Swider C, Stuber F, et al. Tumour necrosis factor alpha promoter gene polymorphism in sarcoidosis. Cytokine 1997;9:787–790.CrossRefPubMedGoogle Scholar
  82. 82.
    Grutters JC, Sato H, Pantelidis P, et al. Increased frequency of the uncommon tumor necrosis factor −857T allele in British and Dutch patients with sarcoidosis. Am J Respir Crit Care Med 2002;165:1119–1124.PubMedGoogle Scholar
  83. 83.
    Yamaguchi E, Itoh A, Hizawa N, et al. The gene polymorphism of tumor necrosis factor-beta, but not that of tumor necrosis factor-alpha, is associated with the prognosis of sarcoidosis. Chest 2001;119:753–761.CrossRefPubMedGoogle Scholar
  84. 84.
    Herry I, Bonay M, Bouchonnet F, et al. Extensive apoptosis of lung T-lymphocytes maintained in vitro. Am J Respir Cell Mol Biol 1996;15:339–347.PubMedGoogle Scholar
  85. 85.
    Kunitake R, Kuwano K, Miyazaki H, et al. Apoptosis in the course of granulomatous inflammation in pulmonary sarcoidosis. Eur Respir J 1999;13:1329–1337.CrossRefPubMedGoogle Scholar
  86. 86.
    Stridh H, Planck A, Gigliotti D, et al. Apoptosis resistant bronchoalveolar lavage (BAL) fluid lymphocytes in sarcoidosis. Thorax 2002;57:897–901.CrossRefPubMedGoogle Scholar
  87. 87.
    Dai H, Guzman J, Costabel U. Increased expression of apoptosis signalling receptors by alveolar macrophages in sarcoidosis. Eur Respir J 1999;13:1451–1454.CrossRefPubMedGoogle Scholar
  88. 88.
    Shikuwa C, Kadota J, Mukae H, et al. High concentrations of soluble Fas ligand in bronchoalveolar lavage fluid of patients with pulmonary sarcoidosis. Respiration 2002;69:242–246.CrossRefPubMedGoogle Scholar
  89. 89.
    Rutherford RM, Staedtler F, Kehren J, et al. Functional genomics and prognosis in sarcoidosis—the critical role of antigen presentation. Sarcoidosis Vasc Diffuse Lung Dis 2004;21:10–18.PubMedGoogle Scholar
  90. 90.
    Xaus J, Besalduch N, Comalada M, et al. High expression of p21 Waf1 in sarcoid granulomas: a putative role for long-lasting inflammation. J Leukoc Biol 2003;74:295–301.CrossRefPubMedGoogle Scholar
  91. 91.
    Daniels CE, Wilkes MC, Edens M, et al. Imatinib mesylate inhibits the profibrogenic activity of TGF-beta and prevents bleomycin-mediated lung fibrosis. J Clin Invest 2004;114:1308–1316.PubMedGoogle Scholar
  92. 92.
    Homma S, Nagaoka I, Abe H, et al. Localization of platelet-derived growth factor and insulin-like growth factor I in the fibrotic lung. Am J Respir Crit Care Med 1995;152:2084–2089.PubMedGoogle Scholar
  93. 93.
    Yoshida Y, Morimoto S, Hiramitsu S, et al. Incidence of cardiac sarcoidosis in Japanese patients with high-degree atrioventricular block. Am Heart J 1997;134:382–386.CrossRefPubMedGoogle Scholar
  94. 94.
    Baughman RP, Teirstein AS, Judson MA, et al. Clinical characteristics of patients in a case control study of sarcoidosis. Am J Respir Crit Care Med 2001;164:1885–1889.PubMedGoogle Scholar
  95. 95.
    Naruse TK, Matsuzawa Y, Ota M, et al. HLA-DQB1*0601 is primarily associated with the susceptibility to cardiac sarcoidosis. Tissue Antigens 2000;56:52–57.CrossRefPubMedGoogle Scholar
  96. 96.
    Takashige N, Naruse TK, Matsumori A, et al. Genetic polymorphisms at the tumour necrosis factor loci (TNFA and TNFB) in cardiac sarcoidosis. Tissue Antigens 1999;54:191–193.CrossRefPubMedGoogle Scholar
  97. 97.
    Hattori N, Niimi T, Sato S, et al. Cytotoxic T-lymphocyte antigen 4 gene polymorphisms in sarcoidosis patients. Sarcoidosis Vasc Diffuse Lung Dis 2005;22:27–32.PubMedGoogle Scholar
  98. 98.
    Sharpe AH, Freeman GJ. The B7-CD28 superfamily. Nat Rev Immunol 2002;2:116–126.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Helmut H. Popper
    • 1
  1. 1.Institute of Pathology, Laboratories for Molecular Cytogenetics, Environmental and Respiratory PathologyMedical University of GrazGrazAustria

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