Sarcoidosis: Are There Sarcoidosis Genes?

  • Helmut H. Popper
Part of the Molecular Pathology Library book series (MPLB, volume 4)


More than 100 years have passed since the first description of sarcoidosis by Hutchinson and the identification of sarcoid granulomas by Besnier, Boeck, and Schaumann, 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 Costimulatory Molecule Human Leukocyte Antigen Class Epithelioid Cell Cardiac Sarcoidosis 
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.


  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.CrossRefPubMedGoogle 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, Klemen H, Churg A, Colby TV. Necrotizing sarcoid granulomatosis – is it different from nodular sarcoidosis? Pneumologie. 2003;57:268–271.CrossRefPubMedGoogle 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 colony-stimulating 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;200:701–705.CrossRefPubMedGoogle 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;321:89–98.CrossRefPubMedGoogle 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 Statl-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 sre 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 GAT A3 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. Thl and Th2 responses regulate experimental lung granuloma development. Sarcoidosis Vasc Diffuse Lung Dis. 1996;13:120–128.PubMedGoogle Scholar
  28. 28.
    Graham DY, Markersich DC, 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. New York: Elsevier; 1988:161–164.Google Scholar
  29. 29.
    Ikonomopouios 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.Google 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-wall-deficient 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.
    Ragno S, Colston MJ, Lowrie DB, 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
  44. 44.
    Huygen K, Content J, Denis O, et al. Immunogenicity and protective efficacy of a tuberculosis DNA vaccine. Nat Med. 1996;2:893–898.CrossRefPubMedGoogle Scholar
  45. 45.
    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
  46. 46.
    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
  47. 47.
    Kirschning CJ, Schumann RR. TLR2: cellular sensor for microbial and endogenous molecular patterns. Curr Top Microbiol Immunol. 2002;270:121–144.PubMedGoogle Scholar
  48. 48.
    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
  49. 49.
    Petzmann S, Maercker C, Markert E, et al. Enhanced proliferation and decreased apoptosis in lung lavage cells of sarcoidosis patients. Sarcoidosis Vasc Diffuse Lung Dis. 2006;23(3):190–200.PubMedGoogle Scholar
  50. 50.
    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
  51. 51.
    McCaskill JG, Chason KD, Hua X, et al. Pulmonary immune responses to Propionibacterium acnes in C57BL/6 and B ALB/c mice. Am J Respir Cell Mol Biol. 2006;35(3):347–356.CrossRefPubMedGoogle Scholar
  52. 52.
    Minami J, Eishi Y, Ishige Y, et al. Pulmonary granulomas caused experimentally in mice by a recombinant trigger-factor protein of Propionibacterium acnes. J Med Dent Sci. 2003;50:265–274.PubMedGoogle Scholar
  53. 53.
    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
  54. 54.
    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
  55. 55.
    Iannuzzi MC, Maliarik MJ, Poisson LM, et al. Sarcoidosis susceptibility and resistance HLA-DQBI alleles in African Americans. Am J Respir Crit Care Med. 2003;167:1225–1231.CrossRefPubMedGoogle Scholar
  56. 56.
    Voorter CE, Drcnt 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
  57. 57.
    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
  58. 58.
    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
  59. 59.
    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
  60. 60.
    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
  61. 61.
    Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol. 2004;4:499–511.CrossRefPubMedGoogle Scholar
  62. 62.
    Leung TF, Tang NL, Wong GW, et al. CD14 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
  63. 63.
    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
  64. 64.
    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
  65. 65.
    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
  66. 66.
    Beutler B. Inferences, questions and possibilities in Toll-like receptor signalling. Nature. 2004;430:257–263.CrossRefPubMedGoogle Scholar
  67. 67.
    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
  68. 68.
    Fukao T, Koyasu S. PI3K and negative regulation of TLR signaling. Trends Immunol. 2003;24:358–363.CrossRefPubMedGoogle Scholar
  69. 69.
    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
  70. 70.
    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
  71. 71.
    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
  72. 72.
    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;152:557–564.PubMedGoogle Scholar
  73. 73.
    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
  74. 74.
    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
  75. 75.
    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
  76. 76.
    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
  77. 77.
    Rossman MD, Thompson B, Frederick M, et al. HLA-DRB1*1101: a significant risk factor for sarcoidosis in blacks and whites. Am J Hum Genet. 2003;73:720–735.CrossRefPubMedGoogle Scholar
  78. 78.
    Sato H, Grutters JC, Pantelidis P, et al. HLA-DQBf *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
  79. 79.
    Foley PJ, McGrath DS, Puscinska E, et al. Human leukocyte antigen-DRBl position 11 residues are a common protective marker for sarcoidosis. Am J Respir Cell Mol Biol. 2001;25:272–277.PubMedGoogle Scholar
  80. 80.
    Seitzer U, Swider C, Stuber F, et al. Tumour necrosis factor alpha promoter gene polymorphism in sarcoidosis. Cytokine. 1997;9:787–790.CrossRefPubMedGoogle Scholar
  81. 81.
    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
  82. 82.
    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
  83. 83.
    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
  84. 84.
    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
  85. 85.
    Stridh H, Planck A, Gigliotti D, et al. Apoptosis resistant bronchoalveolar lavage (BAL) fluid lymphocytes in sarcoidosis. Thorax. 2002;57:897–901.CrossRefPubMedGoogle Scholar
  86. 86.
    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
  87. 87.
    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
  88. 88.
    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
  89. 89.
    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
  90. 90.
    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
  91. 91.
    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
  92. 92.
    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
  93. 93.
    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
  94. 94.
    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
  95. 95.
    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
  96. 96.
    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
  97. 97.
    Sharpe AH, Freeman GJ. The B7–CD28 superfamily. Nat Rev Immunol. 2002;2:116–126.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Helmut H. Popper
    • 1
  1. 1.Department of PathologyMedical University of GrazGrazAustria

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