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DOI: 10.1055/s-2003-39020
Genetics of Sarcoidosis
Publikationsverlauf
Publikationsdatum:
07. Mai 2003 (online)
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ABSTRACT
Sarcoidosis is a systemic disorder of granulomatous inflammation that primarily affects the lung and lymph system, although all organs can be involved. Two principal presentations of the disorder can be defined; an acute form, often with short duration and complete restitution, and a more insidious course with multiorgan involvement and a higher risk of progressive organ damage. Sarcoidosis affects mainly young adults.
The etiology of sarcoidosis is unknown, and current concepts assume one or more environmental triggers that start in a host with an inherited susceptibility to a dysbalanced immune response. Candidate susceptibility genes include genes with a function in antigen recognition, T cell activation, T-helper 1/2 (TH1/TH2) cell balance, and granuloma formation.
A few genetic linkage analyses and numerous association studies with a focus on the region of the major histocompatibility complex genes have been performed, which have so far yielded no breakthrough. They have, rather, verified the assumption of a complex and possibly heterogeneous character of the genetics of sarcoidosis.
KEYWORDS
Sarcoidosis - disease susceptibility - immunogenetics - major histocompatibility complex
REFERENCES
- 1 Hunninghake G W, Costabel U, Ando M. et al . Statement on sarcoidosis. Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999. Am J Respir Crit Care Med . 1999; 160 736-755
- 2 Newman L S, Rose C S, Maier L A. Sarcoidosis. N Engl J Med . 1997; 336 1224-1234
- 3 Müller-Quernheim J. Sarcoidosis: immunopathogenetic concepts and their clinical application. Eur Respir J . 1998; 12 716-738
- 4 Conron M, Du Bois M R. Immunological mechanisms in sarcoidosis. Clin Exp Allergy . 2001; 31 543-554
- 5 Costabel U. Sarcoidosis: clinical update. Eur Respir J . 2001; 18(suppl 32) S56-S68
- 6 Milman N, Hoffmann A L, Byg K E. Sarcoidosis in children: epidemiology in Danes, clinical features, diagnosis, treatment and prognosis. Acta Paediatr . 1998; 87 871-878
- 7 Nowak D A, Widenka D C. Neurosarcoidosis: a review of its intracranial manifestation. J Neurol . 2001; 248 363-372
- 8 Bresnitz E A, Stolley P D, Israel H L, Soper K. Possible risk factors for sarcoidosis: a case-control study. Ann N Y Acad Sci . 1986; 465 632-642
- 9 Rybicki B A, Maliarik M J, Major M, Popovich Jr J, Iannuzzi M C. Epidemiology, demographics, and genetics of sarcoidosis. Semin Respir Infect . 1998; 13 166-173
- 10 Luisetti M, Beretta A, Casali L. Genetic aspects in sarcoidosis. Eur Respir J . 2000; 16 768-780
- 11 McGrath D S, Goh N, Foley P J, du Bois M R. Sarcoidosis: genes and microbes: soil or seed?. Sarcoidosis Vasc Diffuse Lung Dis . 2001; 18 149-164
- 12 Cummings M M. An evaluation of the possible relationship of pine pollen to sarcoidosis (a critical summary). Acta Med Scand Suppl . 1964; 425 48-50
- 13 Terris M, Chaves A D. An epidemiologic study of sarcoidosis. Am Rev Respir Dis . 1966; 94 50-55
- 14 Hillerdal G, Nou E, Osterman K, Schmekel B. Sarcoidosis: epidemiology and prognosis: a 15-year European study. Am Rev Respir Dis . 1984; 130 29-32
- 15 Iwai K. Propionibacterium acnes in sarcoidosis. Sarcoidosis . 1989; 6 73-75
- 16 Kon O M, du Bois M R. Mycobacteria and sarcoidosis. Thorax . 1997; 52(suppl 3) S47-S51
- 17 Grosser M, Luther T, Muller J. et al . Detection of M. tuberculosis DNA in sarcoidosis: correlation with T-cell response. Lab Invest . 1999; 79 775-784
- 18 Eishi Y, Suga M, Ishige I. et al . Quantitative analysis of mycobacterial and propionibacterial DNA in lymph nodes of Japanese and European patients with sarcoidosis. J Clin Microbiol . 2002; 40 198-204
- 19 Edmondstone W M, Wilson A G. Temporal clustering of familial sarcoidosis in nonconsanguineous relatives. Br J Dis Chest . 1984; 78 184-186
- 20 Fite E, Alsina J M, Mana J, Pujol R, Ruiz J, Morera J. Epidemiology of sarcoidosis in Catalonia: 1979-1989. Sarcoidosis Vasc Diffuse Lung Dis . 1996; 13 153-158
- 21 Wilsher M L. Seasonal clustering of sarcoidosis presenting with erythema nodosum. Eur Respir J . 1998; 12 1197-1199
- 22 Padilla M L, Schilero G J, Teirstein A S. Donor-aquired sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis . 2002; 19 18-24
- 23 Bellocq A, Lecossier D, Pierre-Audigier C, Tazi A, Valeyre D, Hance A J. T cell receptor repertoire of T lymphocytes recovered from the lung and blood of patients with sarcoidosis. Am J Respir Crit Care Med . 1994; 149 646-654
- 24 Klein J T, Horn T D, Forman J D, Silver R F, Teirstein A S, Moller D R. Selection of oligoclonal V beta-specific T cells in the intradermal response to Kveim-Siltzbach reagent in individuals with sarcoidosis. J Immunol . 1995; 154 1450-1460
- 25 Grunewald J, Berlin M, Olerup O, Eklund A. Lung T-helper cells expressing T-cell receptor AV2S3 associate with clinical features of pulmonary sarcoidosis. Am J Respir Crit Care Med . 2000; 161 814-818
- 26 James D G. Epidemiology of sarcoidosis. Sarcoidosis . 1992; 9 79-87
- 27 Rybicki B A, Major M, Popovich Jr J, Maliarik M J, Iannuzzi M C. Racial differences in sarcoidosis incidence: a 5-year study in a health maintenance organization. Am J Epidemiol . 1997; 145 234-241
- 28 Edmondstone W M, Wilson A G. Sarcoidosis in Caucasians, blacks, and Asians in London. Br J Dis Chest . 1985; 79 27-36
- 29 Pietinalho A, Hiraga Y, Hosoda Y, Lofroos A B, Yamaguchi M, Selroos O. The frequency of sarcoidosis in Finland and Hokkaido, Japan: a comparative epidemiological study. Sarcoidosis . 1995; 12 61-67
- 30 James D G, Neville E, Siltzbach L E. A worldwide review of sarcoidosis. Ann N Y Acad Sci . 1976; 278 321-334
- 31 Baughman R P, Teirstein A S, Judson M A. et al . Clinical characteristics of patients in a case control study of sarcoidosis. Am J Respir Crit Care Med . 2001; 164 1885-1889
- 32 Pietinalho A, Ohmichi M, Hiraga Y, Lofroos A B, Selroos O. The mode of presentation of sarcoidosis in Finland and Hokkaido, Japan: a comparative analysis of 571 Finnish and 686 Japanese patients. Sarcoidosis Vasc Diffuse Lung Dis . 1996; 13 159-166
- 33 Iwai K, Sekiguti M, Hosoda Y. et al . Racial difference in cardiac sarcoidosis incidence observed at autopsy. Sarcoidosis . 1994; 11 26-31
- 34 Wiman L G, Beskow R. Familial occurrence of sarcoidosis. Scand J Respir Dis Suppl . 1972; 80 115-119
- 35 Kirsten D. Sarcoidosis in Germany: analysis of a questionnaire survey in 1992 of patients of the German Sarcoidosis Group. Pneumologie . 1995; 49 378-382
- 36 Wirnsberger R M, de Vries J, Wouters E F, Drent M. Clinical presentation of sarcoidosis in the Netherlands: an epidemiological study. Neth J Med . 1998; 53 53-60
- 37 McGrath D S, Daniil Z, Foley P. et al . Epidemiology of familial sarcoidosis in the UK. Thorax . 2000; 55 751-754
- 38 Fite E, Alsina J M, Anto J M, Morera J. Sarcoidosis: family contact study. Respiration . 1998; 65 34-39
- 39 Rybicki B A, Iannuzzi M C, Frederick M M. et al . Familial aggregation of sarcoidosis: a case-control etiologic study of sarcoidosis (ACCESS). Am J Respir Crit Care Med . 2001; 164 2085-2091
- 40 MacGregor GA.. Sarcoidosis in husband and wife. Lancet . 1978; 2 941-942
- 41 Newman L S. Immunology, genetics, and epidemiology of beryllium disease. Chest . 1996; 109(suppl 3) S40-S43
- 42 Saltini C, Amicosante M. Beryllium disease. Am J Med Sci . 2001; 321 89-98
- 43 Blau E B. Familial granulomatous arthritis, iritis, and rash. J Pediatr . 1985; 107 689-693
- 44 Manouvrier-Hanu S, Puech B, Piette F. et al . Blau syndrome of granulomatous arthritis, iritis, and skin rash: a new family and review of the literature. Am J Med Genet . 1998; 76 217-221
- 45 Kreiss K, Mroz M M, Zhen B, Martyny J W, Newman L S. Epidemiology of beryllium sensitization and disease in nuclear workers. Am Rev Respir Dis . 1993; 148 985-991
- 46 Newman L S. Beryllium disease and sarcoidosis: clinical and laboratory links. Sarcoidosis . 1995; 12 7-19
- 47 Richeldi L, Sorrentino R, Saltini C. HLA-DPB1 glutamate 69: a genetic marker of beryllium disease. Science . 1993; 262 242-244
- 48 Saltini C, Richeldi L, Losi M. et al . Major histocompatibility locus genetic markers of beryllium sensitization and disease. Eur Respir J . 2001; 18 677-684
- 49 Rossman M D, Stubbs J, Lee C W, Argyris E, Magira E, Monos D. Human leukocyte antigen Class II amino acid epitopes: susceptibility and progression markers for beryllium hypersensitivity. Am J Respir Crit Care Med . 2002; 165 788-794
- 50 Maier L A, Sawyer R T, Bauer R A. et al . High beryllium-stimulated TNF-alpha is associated with the -308 TNF-alpha promoter polymorphism and with clinical severity in chronic beryllium disease. Am J Respir Crit Care Med . 2001; 164 1192-1199
- 51 Amicosante M, Sanarico N, Berretta F. et al . Beryllium binding to HLA-DP molecule carrying the marker of susceptibility to berylliosis glutamate beta 69. Hum Immunol . 2001; 62 686-693
- 52 James G. Blau's syndrome and sarcoidosis. Lancet . 1999; 354 1035
- 53 Tromp G, Kuivaniemi H, Raphael S. et al . Genetic linkage of familial granulomatous inflammatory arthritis, skin rash, and uveitis to chromosome 16. Am J Hum Genet . 1996; 59 1097-1107
- 54 Podolsky D K. Inflammatory bowel disease. N Engl J Med . 1991; 325 928-937
- 55 Hugot J P, Laurent-Puig P, Gower-Rousseau C. et al . Mapping of a susceptibility locus for Crohn's disease on chromosome 16. Nature . 1996; 379 821-823
- 56 Cavanaugh J A, Callen D F, Wilson S R. et al . Analysis of Australian Crohn's disease pedigrees refines the localization for susceptibility to inflammatory bowel disease on chromosome 16. Ann Hum Genet . 1998; 62 291-298
- 57 Hugot J P, Chamaillard M, Zouali H. et al . Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature . 2001; 411 599-603
- 58 Ogura Y, Bonen D K, Inohara N. et al . A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature . 2001; 411 603-606
- 59 Hampe J, Cuthbert A, Croucher P J. et al . Association between insertion mutation in NOD2 gene and Crohn's disease in German and British populations. Lancet . 2001; 357 1925-1928
- 60 Miceli-Richard C, Lesage S, Rybojad M. et al . CARD15 mutations in Blau syndrome. Nat Genet . 2001; 29 19-20
- 61 Iannuzzi M C. Genetics of sarcoidosis. Monaldi Arch Chest Dis . 1998; 53 609-613
- 62 Rybicki B A, Maliarik M J, Major M, Popovich Jr J, Iannuzzi M C. Genetics of sarcoidosis. Clin Chest Med . 1997; 18 707-717
- 63 Verleden G M, du Bois M R, Bouros D. et al . Genetic predisposition and pathogenetic mechanisms of interstitial lung diseases of unknown origin. Eur Respir J . 2001; 32(suppl) S17-S29
- 64 Schürmann M, Reichel P, Müller-Myhsok B, Schlaak M, Müller-Quernheim J, Schwinger E. Results from a genome-wide search for predisposing genes in sarcoidosis. Am J Respir Crit Care Med . 2001; 164 840-846
- 65 Lander E, Kruglyak L. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet . 1995; 11 241-247
- 66 Rybicki B A, Maliarik M J, Bock C H. et al . The Blau syndrome gene is not a major risk factor for sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis . 1999; 16 203-208
- 67 Möller E, Hedfors E, Wiman L G. HL-A genotypes and MLR in familial sarcoidosis. Tissue Antigens . 1974; 4 299-305
- 68 Ina Y, Takada K, Yamamoto M, Morishita M, Senda Y, Torii Y. HLA and sarcoidosis in the Japanese. Chest . 1989; 95 1257-1261
- 69 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
- 70 Berlin M, Fogdell-Hahn A, Olerup O, Eklund A, Grunewald J. HLA-DR predicts the prognosis in Scandinavian patients with pulmonary sarcoidosis. Am J Respir Crit Care Med . 1997; 156 1601-1605
- 71 Foley P J, McGrath D S, 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
- 72 Planck A, Eklund A, Yamaguchi E, Grunewald J. Angiotensin-converting enzyme gene polymorphism in relation to HLA-DR in sarcoidosis. J Intern Med . 2002; 251 217-222
- 73 Seitzer U, Gerdes J, Müller-Quernheim J. Evidence for disease phenotype associated haplotypes (DR.TNF) in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis . 2001; 18 279-283
- 74 Lympany P A, Petrek M, Southcott A M. et al . HLA-DPB polymorphisms: Glu 69 association with sarcoidosis. Eur J Immunogenet . 1996; 23 353-359
- 75 Foley P J, Lympany P A, Puscinska E, Zielinski J, Welsh K I, du Bois M R. Analysis of MHC encoded antigen-processing genes TAP1 and TAP2 polymorphisms in sarcoidosis. Am J Respir Crit Care Med . 1999; 160 1009-1014
- 76 Maliarik M J, Chen K M, Major M L. et al . Analysis of HLA-DPB1 polymorphisms in African Americans with sarcoidosis. Am J Respir Crit Care Med . 1998; 158 111-114
- 77 Schürmann M, Bein G, Kirsten D, Schlaak M, Müller-Quernheim J, Schwinger E. HLA-DQB1 and HLA-DPB1 genotypes in familial sarcoidosis. Respir Med . 1998; 92 649-652
- 78 Schürmann M, Lympany P A, Reichel P. et al . Familial sarcoidosis is linked to the major histocompatibility complex region. Am J Respir Crit Care Med . 2000; 162 861-184
- 79 Tomlinson I P, Bodmer W F. The HLA system and the analysis of multifactorial genetic disease. Trends Genet . 1995; 11 493-498
- 80 Moller D R. Cells and cytokines involved in the pathogenesis of sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis . 1999; 16 24-31
- 81 Murakozy G, Gaede K I, Zissel G, Schlaak M, Müller-Quernheim J. Analysis of gene polymorphisms in interleukin-10 and transforming growth factor beta 1 in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis . 2001; 18 165-169
- 82 Niimi T, Sato S, Tomita H. et al . Lack of association with interleukin-1 receptor antagonist and interleukin-1beta gene polymorphisms in sarcoidosis patients. Respir Med . 2000; 94 1038-1042
- 83 Rybicki B A, Maliarik M J, Malvitz E. et al . The influence of T cell receptor and cytokine genes on sarcoidosis susceptibility in African Americans. Hum Immunol . 1999; 60 867-874
- 84 Seitzer U, Swider C, Stuber F. et al . Tumour necrosis factor alpha promoter gene polymorphism in sarcoidosis. Cytokine . 1997; 9 787-790
- 85 Labunski S, Posern G, Ludwig S, Kundt G, Brocker E B, Kunz M. Tumour necrosis factor-alpha promoter polymorphism in erythema nodosum. Acta Derm Venereol . 2001; 81 18-21
- 86 Grutters J C, 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
- 87 Takashige N, Naruse T K, Matsumori A. et al . Genetic polymorphisms at the tumour necrosis factor loci (TNFA and TNFB) in cardiac sarcoidosis. Tissue Antigens . 1999; 54 191-193
- 88 Lieberman J. Elevation of serum angiotensin-converting-enzyme (ACE) level in sarcoidosis. Am J Med . 1975; 59 365-372
- 89 Gilbert S, Steinbrech D S, Landas S K, Hunninghake G W. Amounts of angiotensin-converting enzyme mRNA reflect the burden of granulomas in granulomatous lung disease. Am Rev Respir Dis . 1993; 148 483-486
- 90 Sharma P, Smith I, Maguire G, Stewart S, Shneerson J, Brown M J. Clinical value of ACE genotyping in diagnosis of sarcoidosis. Lancet . 1997; 31(349) 1602-1603
- 91 Furuya K, Yamaguchi E, Itoh A. et al . Deletion polymorphism in the angiotensin I converting enzyme (ACE) gene as a genetic risk factor for sarcoidosis. Thorax . 1996; 51 777-780
- 92 Arbustini E, Grasso M, Leo G. et al . Polymorphism of angiotensin-converting enzyme gene in sarcoidosis. Am J Respir Crit Care Med . 1996; 153 851-854
- 93 Tomita H, Ina Y, Sugiura Y. et al . Polymorphism in the angiotensin-converting enzyme (ACE) gene and sarcoidosis. Am J Respir Crit Care Med . 1997; 156 255-259
- 94 McGrath D S, Foley P J, Petrek M. et al . Ace gene I/D polymorphism and sarcoidosis pulmonary disease severity. Am J Respir Crit Care Med . 2001; 15(164) 197-201
- 95 Pietinalho A, Furuya K, Yamaguchi E, Kawakami Y, Selroos O. The angiotensin-converting enzyme DD gene is associated with poor prognosis in Finnish sarcoidosis patients. Eur Respir J . 1999; 13 723-726
- 96 Papadopoulos K I, Melander O, Orho-Melander M, Groop L C, Carlsson M, Hallengren B. Angiotensin converting enzyme (ACE) gene polymorphism in sarcoidosis in relation to associated autoimmune diseases. J Intern Med . 2000; 247 71-27
- 97 Maliarik M J, Rybicki B A, Malvitz E. et al . Angiotensin-converting enzyme gene polymorphism and risk of sarcoidosis. Am J Respir Crit Care Med . 1998; 158 1566-1570
- 98 Schürmann M, Reichel P, Müller-Myhsok B. et al . Angiotensin-converting enzyme (ACE) gene polymorphisms and familial occurrence of sarcoidosis. J Intern Med . 2001; 249 77-83
- 99 Rutherford R M, Kehren J, Staedtler F. et al . Functional genomics in sarcoidosis: reduced or increased apoptosis?. Swiss Med Wkly . 2001; 131 459-470
- 100 Thonhofer E, Maercker C, Popper H H. Expression of sarcoidosis-related genes in lung lavage cells. Sarcoidosis Vasc Diffuse Lung Dis . 2002; 19 59-64