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Respiratory Research
Published in: Respiratory Research 1/2001

Open Access 01-12-2001 | Review

Genotyping in the MHC locus: potential for defining predictive markers in sarcoidosis

Authors: Ulrike Seitzer, Johannes Gerdes, Joachim Müller-Quernheim

Published in: Respiratory Research | Issue 1/2001

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Abstract

In sarcoidosis, host genetic factors are discussed as contributing to disease susceptibility and course. Since tumor necrosis factor (TNF)-α is a central mediator of granuloma formation and since elevated TNF-α levels are found during active phases of sarcoidosis, genetic polymorphisms correlating with influences on TNF-α levels are of special interest. The complete sequencing of the MHC region and the increase in the number of identified gene polymorphisms in this locus associated with TNF-α production offer the opportunity of detecting new genes associated with sarcoidosis and perhaps of defining disease-associated haplotypes that bear the potential of serving as predictive markers for this disease.
Literature
1.
Muller-Quernheim J: Sarcoidosis: immunopathogenetic concepts and their clinical application. Eur Respir J. 1998, 12: 716-738. 10.1183/09031936.98.12030716.PubMedCrossRef
2.
Luisetti M, Beretta A, Casali L: Genetic aspects in sarcoidosis. Eur Respir J. 2000, 16: 768-780. 10.1034/j.1399-3003.2000.16d31.x.PubMedCrossRef
3.
Hunninghake GW, Costabel U, Ando M, Baughman R, Cordier JF, du Bois RM, Eklund A, Kitaichi M, Lynch J, Rizzato G, Rose C, Selroos O, Semenzato G, Sharma OP: Statement on sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 1999, 16: 149-173.PubMed
4.
Gran JT, Bohmer E: Acute sarcoid arthritis: a favourable outcome?. Scand J Rheumatol. 1996, 25: 70-73.PubMedCrossRef
5.
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.PubMedCrossRef
6.
Myatt N, Coghill G, Morrison K, Jones D, Cree IA: Detection of tumour necrosis factor alpha in sarcoidosis and tuberculosis granulomas using in situ hybridization. J Clin Pathol. 1994, 47: 423-426.PubMedPubMedCentralCrossRef
7.
Bergeron A, Bonay M, Kambouchner M, Lecossier D, Riquet M, Soler P, Hance A, Tazi A: Cytokine patterns in tuberculous and sarcoid granulomas: correlations with histopathologic features of the granulomatous response. J Immunol. 1997, 159: 3034-3043.PubMed
8.
Bachwich PR, Lynch JP, Larrick J, Spengler M, Kunkel S: Tumor necrosis factor production by human sarcoid alveolar macrophages. Am J Pathol. 1986, 125: 421-425.PubMedPubMedCentral
9.
Müller-Quernheim J, Pfeiffer S, Männel D, Strausz J, Ferlinz R: Lung-restricted activation of the alveolar macrophage/monocyte system in pulmonary sarcoidosis. Am Rev Respir Dis. 1992, 145: 187-192.PubMedCrossRef
10.
Somoskövi A, Zissel G, Seitzer U, Gerdes J, Schlaak M, Müller-Quernheim J: Polymorphisms at position -308 in the promoter region of the TNFalpha and in the first intron of the TNFbeta genes and spontaneous and lipopolysaccharide-induced TNFalpha release in sarcoidosis. Cytokine. 1999, 11: 882-887. 10.1006/cyto.1999.0498.PubMedCrossRef
11.
Ziegenhagen M, Benner U, Zissel G, Zabel P, Schlaak M, Müller-Quernheim J: Sarcoidosis: TNFalpha release from alveolar macrophages and serum level of sIL-2R are prognostic markers. Am J Crit Respir Care Med. 1997, 156: 1586-1592.CrossRef
12.
Bendtzen K, Morling N, Fomsgaard A, Svenson M, Jacobsen B, Odum N, Svejgaard A: Association between HLA-DR2 and production of tumour necrosis factor alpha and interleukin 1 by mononuclear cells activated by lipopolysaccharide. Scand J Immunol. 1988, 28: 599-606.PubMedCrossRef
13.
Jacob CO, Fronek Z, Lewis GD, Koo M, Hansen JA, McDevitt HO: Heritable major histocompatibility complex class II-associated differences in production of tumor necrosis factor alpha: relevance to genetic predisposition to systemic lupus erythe-matosus. Proc Natl Acad Sci USA. 1990, 87: 1233-1237.PubMedPubMedCentralCrossRef
14.
15.
Aguado B, Milner CM, Campbell RD: Genes of the MHC class III region and the functions of the proteins they encode. In HLA and MHC: Genes, Molecules and Function. Edited by Browning M, McMichael A. Oxford: BIOS Scientific Publishers;. 1996, 39-75.
16.
Abraham LJ, French MAH, Dawkins RL: Polymorphic MHC ancestral haplotypes affect the activity of tumour necrosis factor alpha. Clin Exp Immunol. 1993, 92: 14-18.PubMedPubMedCentralCrossRef
17.
Wilson AG, de Vries N, Pociot F, di Giovine FS, van der Putte LBA, Duff GW: An allelic polymorphism within the human tumor necrosis factor alpha promoter region is strongly associated with HLA A1, B8, and DR3 alleles. J Exp Med. 1993, 177: 557-560.PubMedCrossRef
18.
Price P, Witt C, Allcock R, Sayer D, Garlepp M, Kok CC, French M, Mallal S, Christiansen F: The genetic basis for the association of the 8.1 ancestral haplotype (A1, B8, DR3) with multiple immunopathological diseases. Immunol Rev. 1999, 167: 257-274.PubMedCrossRef
19.
Mori M, Beatty PG, Graves M, Boucher KM, Milford EL: HLA gene and haplotype frequencies in the North American population. Transplantation. 1997, 64: 1017-1027. 10.1097/00007890-199710150-00014.PubMedCrossRef
20.
Ishihara M, Ohno S, Mizuki N, Yamagata N, Ishida T, Naruse T, Kuwata H: Genetic polymorphism of the major histocompatibility complex-antigen-processing genes TAP and LMP in sarcoidosis. Hum Immunol. 1996, 45: 105-110. 10.1016/0198-8859(95)00167-0.PubMedCrossRef
21.
Ishihara M, Ohno S, Ishida T, Naruse T, Kagiya M, Mizuki N, Maruya E, Saji H, Inoko H: Analysis of allelic variation of the TAP2 gene in sarcoidosis. Tissue Antigens. 1997, 49: 107-110.PubMedCrossRef
22.
Pasturenzi L, Martinetti M, Cuccia M, Cipriani A, Semenzato G, Luisetti M: HLA class I, II, and III polymorphism in Italian patients with sarcoidosis. Chest. 1993, 104: 1170-1175.PubMedCrossRef
23.
Foley PJ, Lympany PA, Puscinska E, Zielinski J, Welsh KI, du Bois RM: Analysis of MHC encoded antigen-processing genes TAP1 and TAP2 polymorphisms in sarcoidosis. Am J Respir Crit Care Med. 1999, 160: 1009-1014.PubMedCrossRef
24.
Schürmann M, Lympany PA, Reichel P, Müller-Myhsok B, Wurm K, Schlaak M, Müller-Quernheim J, du Bois RM, Schwinger E: Familial sarcoidosis is linked to the major histocompatibility complex region. Am J Respir Crit Care Med. 2000, 162: 861-864.PubMedCrossRef
25.
Schürmann M, Reichel P, Müller-Myhsok B, Schlaak M, Müller-Quernheim J, Schwinger E: Results from a genomewide search for predisposing genes in sarcoidosis. Am J Respir Crit Care Med. 2001, 164: 840-846.PubMedCrossRef
26.
Maliarik MJ, Rybicki BA, Malvitz E, Sheffer RG, Major M, Popovich J, Iannuzzi MC: Angiotensin-converting enzyme gene polymorphism and risk of sarcoidosis. Am J Resp Crit Care Med. 1998, 158: 1566-1570.PubMedCrossRef
27.
Papadopoulos KI, Melander O, Orho-Melander M, Groop LC, Carlsson M, Hallengren B: Angiotensin converting enzyme (ACE) gene polymorphism in sarcoidosis in relation to associated autoimmune diseases. J Intern Med. 2000, 247: 71-77. 10.1046/j.1365-2796.2000.00575.x.PubMedCrossRef
28.
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. 10.1183/09031936.99.13472399.PubMedCrossRef
29.
Arbustini E, Grasso M, Leo G, Tinelli C, Fasani R, Diegoli M, Banchieri N, Cipriani A, Gorrini M, Semenzato G, Luisetti M: Polymorphism of angiotensin-converting enzyme gene in sarcoidosis. Am J Respir Crit Care Med. 1996, 153: 851-854.PubMedCrossRef
30.
Furuya K, Yamaguchi E, Itoh A, Hizawa N, Ohnuma N, Kojima J, Kodama N, Kawakami Y: Deletion polymorphism in the angiotensin I converting enzyme (ACE) gene as a genetic risk factor for sarcoidosis. Thorax. 1996, 51: 777-780.PubMedPubMedCentralCrossRef
31.
Tomita H, Ina Y, Sugiura Y, Sato S, Kawaguchi H, Morishita M, Yamamoto M, Ueda R: Polymorphism in the angiotensin-converting enzyme (ACE) gene and sarcoidosis. Am J Respir Crit Care Med. 1997, 156: 255-259.PubMedCrossRef
32.
Schürmann M, Reichel P, Müller-Myhsok B, Dieringer T, Wurm K, Schlaak M, Müller-Quernheim J, Schwinger E: Angiotensin-converting enzyme (ACE) gene polymorphisms and familial occurrence of sarcoidosis. J Intern Med. 2001, 249: 77-83. 10.1046/j.1365-2796.2001.00776.x.PubMedCrossRef
33.
Hosoda Y, Yamaguchi M, Hiraga Y: Global epidemiology of sarcoidosis. What story do prevalence and incidence tell us?. Clin Chest Med. 1997, 18: 681-694.PubMedCrossRef
34.
Rafnsson V, Ingimarsson O, Hjalmarsson I, Gunnarsdottir H: Association between exposure to crystalline silica and risk of sarcoidosis. Occup Environ Med. 1998, 55: 657-660.PubMedPubMedCentralCrossRef
35.
Richeldi L, Sorrentino R, Saltini C: HLA-DPB1 glutamate 69: a genetic marker of beryllium disease. Science. 1993, 262: 242-244.PubMedCrossRef
36.
Newman LS: Metals that cause sarcoidosis. Semin Respir Infect. 1998, 13: 212-220.PubMed
37.
Rose CS, Martyny JW, Newman LS, Milton DK, King TE, Beebe JL, McCammon JB, Hoffman RE, Kreiss K: 'Lifeguard lung': endemic granulomatous pneumonitis in an indoor swimming pool. Am J Public Health. 1998, 88: 1795-1800.PubMedPubMedCentralCrossRef
38.
Newman LS: Beryllium disease and sarcoidosis: clinical and laboratory links. Sarcoidosis. 1995, 12: 7-19.PubMed
39.
Smith MJ, Turton CWG, Mitchell DN, Turner-Warwick M, Morris LM, Lawler SD: Association of HLA B8 with spontaneous resolution in sarcoidosis. Thorax. 1981, 36: 296-298.PubMedPubMedCentralCrossRef
40.
Hedfors E, Lindström F: HLA-B8/DR3 in sarcoidosis. Correlation to acute onset disease with arthritis. Tissue Antigens. 1983, 22: 200-203.PubMedCrossRef
41.
42.
Kremer JM: Histologic findings in siblings with acute sarcoid arthritis: association with the B8, DR3 phenotype. J Rheumatol. 1986, 13: 593-597.PubMed
43.
Krause A, Goebel KM: Class II MHC antigen (HLA-DR3) predisposes to sarcoid arthritis. J Clin Lab Immunol. 1987, 24: 25-27.PubMed
44.
Seitzer U, Swider C, Stüber F, Suchnicki K, Lange A, Richter E, Zabel P, Müller-Quernheim J, Flad H-D, Gerdes J: Tumor necrosis factor alpha promoter gene polymorphism in sarcoidosis. Cytokine. 1997, 9: 787-790. 10.1006/cyto.1997.0224.PubMedCrossRef
45.
Odum N, Milman N, Jacobsen BK, Georgsen J, Svejgaard A: HLA class II (DR, DQ, DP) in patients with sarcoidosis: evidence of an increased frequency of DRw6. Exp Clin Immunogenet. 1991, 8: 227-232.PubMed
46.
Martinetti M, Tinelli C, Kolek V, Cuccia M, Salvaneschi L, Pasturenzi L, Semenzato G, Cipriani A, Bartova A, Luisetti M: '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.PubMedCrossRef
47.
Swider C, Schnittger L, Bogunia-Kubik K, Gerdes J, Flad H-D, Lange A, Seitzer U: TNFA and HLA-DR genotyping as potential prognostic markers in pulmonary sarcoidosis. Eur Cytokine Network. 1999, 10: 143-146.
48.
Wilson AG, Symons JA, McDowell TL, McDevitt HO, Duff GW: Effects of a polymorphism in the human tumor necrosis factor alpha promotor on transcriptional activation. Proc Natl Acad Sci USA. 1997, 94: 3195-3199. 10.1073/pnas.94.7.3195.PubMedPubMedCentralCrossRef
49.
Seitzer U, Gerdes J, Müller-Quernheim J: Evidence of disease phenotype associated haplotypes (DR.TNF) in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2001, 18: 279-283.PubMed
50.
Takashige N, Naruse TK, Matsumori A, Hara M, Nagai S, Morimoto S, Hiramitsu S, Sasayama S, Inoko H: Genetic polymorphisms at the tumour necrosis factor loci (TNFA and TNFB) in cardiac sarcoidosis. Tissue Antigens. 1999, 54: 185-190. 10.1034/j.1399-0039.1999.540210.x.CrossRef
51.
Yamaguchi E, Itoh A, Hizawa N, Kawakami Y: The gene polymorphism of tumor necrosis factor-β, but not that of tumor necrosis factor-α, is associated with the prognosis of sarcoidosis. Chest. 2001, 119: 753-761. 10.1378/chest.119.3.753.PubMedCrossRef
52.
Beck S, Geraghty D, Inoko H, Rowen L, corresponding authors of the MHC Sequencing Consortium: Complete sequence and gene map of a human major histocompatibility complex. Nature. 1999, 401: 921-923. 10.1038/44853.CrossRef
Metadata
Title
Genotyping in the MHC locus: potential for defining predictive markers in sarcoidosis
Authors
Ulrike Seitzer
Johannes Gerdes
Joachim Müller-Quernheim
Publication date
01-12-2001
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2001
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/rr178

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