Human leukocyte antigen associations in Finnish liver transplantations due to primary sclerosing cholangitis and primary biliary cirrhosis
Languages of publication
A genetic predisposition has been suggested in primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC). The aim of the study was to evaluate human leukocyte antigen (HLA) frequencies and HLA associations in Finnish PSC and PBC patients. The relative frequencies of HLA-A,-B, and-DR antigens were compared between patients with PSC (n=50), or PBC (n=89), transplanted due to end-stage liver disease, and healthy members in the Finnish bone marrow donor registry (n=10000). Prevalence differences, prevalence ratios and the associated large-sample significance probabilities (2-sided P-values) and 95% confidence intervals were calculated.We found a strong positive association between PSC and HLA-B8 and-DR3, and a weak positive association between HLA-A1 and PSC. HLA-DR3 also had a weak positive association with PBC, and a weak negative association between HLA-DR5 and PBC was found. In conclusion, HLA-B8, and-DR3 are susceptible for progressive liver disease in PSC, and HLA-DR3 may also be susceptible for disease progression in PBC. HLA-DR5 may be protective against severe PBC.
1 - 3 - 2007
1 - 3 - 2007
- Department of Clinical Chemistry, Laboratory Center, Kuopio University Hospital and Kuopio University, FIN-70211, Kuopio, Finland, email@example.com
- Department of Public Health, University of Helsinki, and Finnish Institute of Occupational Health, Helsinki, Finland, firstname.lastname@example.org
- Transplantation and Liver Surgery Clinic, Department of Surgery, Helsinki University Hospital, Helsinki, Finland, email@example.com
-  K.M. Boberg, A. Bergquist, S. Mitchell, A. Pares, F. Rosina and U. Broomé: “Cholangiocarcinoma in primary sclerosing cholangitis: Risk factors and clinical presentation”, Scand J. Gastroenterol., Vol. 37, (2002), pp. 1205–1211. http://dx.doi.org/10.1080/003655202760373434[Crossref]
-  B. Brandsaeter, H. Isoniemi, U. Broomé, M. Olausson, L. Bäckman and B. Hansen: “Liver transplantation for primary sclerosing cholangitis; predictors and consequences of hepatobiliary malignancy”, J. Hepatol., Vol. 40, (2004), pp. 815–822. http://dx.doi.org/10.1016/j.jhep.2004.01.002[Crossref]
-  K. Bjoro and E. Schrumpf: “Liver transplantation for primary sclerosing cholangitis”, J. Hepatol., Vol. 40, (2004), pp. 570–577. http://dx.doi.org/10.1016/j.jhep.2004.01.021[Crossref]
-  U. Broomé, H. Glaumann, R. Hultcrantz and U. Forsum: “Distribution of HLA-DR, HLA-DP, HLA-DQ antigens in liver tissue from patients with primary sclerosing cholangitis”, Scand J. Gastroenterol, Vol. 25, (1990), pp. 54–58.
-  A. Bergquist, G. Lindberg, S. Saarinen and U. Broomé: “Increased prevalence of primary sclerosing cholangitis among first-degree relatives”, J. Hepatol., Vol. 42, (2005), pp. 252–256. http://dx.doi.org/10.1016/j.jhep.2004.10.011[Crossref]
-  C. Selmi, P. Invernizzi, M. Zuin, M. Podda, M.F. Seldin and M.E. Gershwin: “Genes and (auto)immunity in primary biliary cirrhosis”, Genes Immun., Vol. 6, (2005), pp. 543–556. http://dx.doi.org/10.1038/sj.gene.6364248[Crossref]
-  J.J. Feld and E.J. Heathcote: “Epidemiology of autoimmune liver disease”, J Gastroenterol. Hepatol., Vol. 18, (2003), pp. 1118–1128. http://dx.doi.org/10.1046/j.1440-1746.2003.03165.x[Crossref]
-  C. Barbatis, P. Kelly, J. Greveson, A. Heryet and J. McGee: “Immunocytochemical analysis of HLA class II (DR) antigens in liver disease in man”, J. Clin. Pathol., Vol. 40, (1987), pp. 879–884. [Crossref]
-  R.W. Chapman, Z. Varghese, R. Gaul, G. Patel, N. Kokinon and S. Sherlock: “Association of primary sclerosing cholangitis with HLA-B8”, Gut, Vol. 24, (1983), pp. 38–41. [Crossref]
-  O. Olerup, R. Olsson, R. Hultcrantz and U. Broome: “HLA-DR and HLA-DQ are not markers for rapid disease progression in primary sclerosing cholangitis”, Gastroenterology, Vol. 108, (1995), pp. 870–878. http://dx.doi.org/10.1016/0016-5085(95)90463-8[Crossref]
-  A. Spurkland, S. Saarinen, K.M. Boberg, S. Mitchell, U. Broome and L. Caballeria: “HLA class II haplotypes in primary sclerosing cholangitis patients from five European populations”, Tissue Antigens, Vol. 53, (1999), pp. 459–469. http://dx.doi.org/10.1034/j.1399-0039.1999.530502.x[Crossref]
-  S. Saarinen, O. Olerup and U. Broomé: “Increased frequency of autoimmune diseases in patients with primary sclerosing cholangitis”, Am. J. Gastroenterol., Vol. 95, (2000), pp. 3195–3199. http://dx.doi.org/10.1111/j.1572-0241.2000.03292.x[Crossref]
-  J.M. Farrant, D.G. Doherty, P.T. Donaldson, R.W. Vaughan, K.M. Hayllar and K.I. Welsh: “Amino acid substitutions at position 38 of the DRβ polypeptide confer susceptibility to and protection from primary sclerosing cholangitis”, Hepatology, Vol. 16, (1992), pp. 390–395. [Crossref]
-  W.Z. Mehal, Y.-M.D. Lo, B.P. Wordsworth, J.M. Neuberger, S.C. Hubscher, K.A. Fleming and R.W. Chapman: “HLA DR4 is a marker for rapid disease progression in primary sclerosing cholangitis”, Gastroenterology, Vol. 106, (1994), pp. 160–167.
-  K.M. Boberg, A. Spurkland, G. Rocca, T. Egeland, S. Saarinen and S. Mitchell: “The HLA-DR3,DQ2 heterozygous genotype is associated with an accelerated progression of primary sclerosing cholangitis”, Scand. J. Gastroenterol., Vol. 36, (2001), pp. 886–890. http://dx.doi.org/10.1080/003655201750313441
-  G.J. Gores, S.B. Moore, L.D. Fisher, F.C. Powell and E.R. Dickson: “Primary biliary cirrhosis: associations with class II major histocompatibility complex antigens”, Hepatology, Vol. 7, (1987), pp. 889–892. [Crossref]
-  D.E. Johnston, M.M. Kaplan, K.B. Miller, C.M. Connors and E.L. Milford: “Histo-compatibility antigens in primary biliary cirrhosis”, Am. J. Gastroenterol., Vol. 82, (1987), pp. 1127–1129.
-  M.P. Manns, A. Bremm, P.M. Schneider, A. Notghi, G. Gerken and M. Prager-Eberle: “HLA DRw8 and complement C4 deficiency as risk factors in primary biliary cirrhosis”, Gastroenterology, Vol. 101, (1991), pp. 1367–1373.
-  J. Underhill, P. Donaldson, G. Bray, D. Doherty, B. Portmann and R. Williams: “Susceptibility to primary biliary cirrhosis is associated with the HLA-DR8-DQB1*0402 haplotype”, Hepatology, Vol. 16, (1992), pp. 1404–1408.
-  N. Morling, K. Dalhoff, L. Fugger, J. Georgsen, B. Jakobsen and L. Ranek: “DNA polymorphism of HLA calss II genes in primary biliary cirrhosis”, Immunogenetics, Vol. 35, (1992), pp. 112–116.
-  W.L. Gregory, W. Mehal, A.N. Dunn, G. Cavanagh, R. Chapman and K.A. Fleming: “Primary biliary cirrhosis: contribution of HLA class II allele DR8”, QJM-Int. J. Med., Vol. 86, (1993), pp. 393–399.
-  A.B. Begovich, W. Klitz, P.V. Moonsamy, J. Van de Water, G. Peltz and M.E. Gershwin: “Genes within the HLA class II region confer both predisposition and resistance to primary biliary cirrhosis”, Tissue Antigens, Vol. 43, (1994), pp. 71–77. [Crossref]
-  G. Ercilla, A. Parés, F. Arriaga, M. Bruguera, R. Castillo, J. Rodés and J. Vives: “Primary biliary cirrhosis associated with HLA-Drw3”, Tissue Antigens, Vol. 14, (1979), pp. 449–452. http://dx.doi.org/10.1111/j.1399-0039.1979.tb00874.x[Crossref]
-  B. Brandsaeter, S. Friman, U. Broome, H. Isoniemi, M. Olausson and L. Bäckman: “Outcome following liver transplantation for primary sclerosing cholangitis in the Nordic Countries”, Scand. J. Gastroenterol., Vol. 38, (2003), 1176–1183. http://dx.doi.org/10.1080/00365520310006009[Crossref]
-  M.K. Sirén, H. Sareneva, M.L. Lokki and S. Koskimies: “Unique HLA antigen frequencies in the Finnish population”, Tissue Antigens, Vol. 48, (1996), pp. 703–707. http://dx.doi.org/10.1111/j.1399-0039.1996.tb02695.x[Crossref]
-  O. Miettinen and M. Nurminen: “Comparative analysis of two rates”, Stat. Med., Vol. 4, (1985), pp. 213–226.
-  StatXact 5, Statistical software for exact nonparametric inference, CYTEL Software Corporation, Cambridge, MA, 2001.
-  S. Wacholder, S. Chanock, M. Garcia-Closas, L. El ghormli and N. Rothman: “Assessing the probability of false positive reports in molecular epidemiology studies”, J. Nat. Cancer Inst., Vol. 96, (2004), pp. 424–442. Website for calculating the probability: http://jncicancerspectrum.oxfordjournals.org/content/vol96/issue6/images/data/434/DC1/Wacholder_FPRP_prototype_spreadsheet_040227.xls http://dx.doi.org/10.1093/jnci/djh088[Crossref]
-  K. Wiencke, A. Spurkland, E. Schrumpf and K.M. Boberg: “Primary sclerosing cholangitis is associated to an extended B8-DR3 haplotype including particular MICA and MICB alleles”, Hepatology, Vol. 34, (2001), pp. 625–630. [Crossref]
-  H. Zetterquist, U. Broome, K. Einarsson and O. Olerup: “HLA class II genes in primary sclerosing cholangitis and chronic inflammatory bowel disease: no HLA-DRw52a association in Swedish patients with sclerosing cholangitis”, Gut, Vol. 33, (1992), pp. 942–946. [Crossref]
-  E. Schrumpf, O. Fausa, O. Forre, J.H. Dobloug, S. Ritland and E. Thorsby: “HLA antigens and immunoregulatory T cells in ulcerative colitis associated with hepatobiliary disease”, Scand. J. Gastroenterol., Vol. 17, (1982), pp. 187–191. http://dx.doi.org/10.3109/00365528209182038[Crossref]
-  P.T. Donaldson, D.G. Doherty, K.M. Hayllar, I.G. McFarlane, P.J. Johnson, R. Williams: “Susceptibility to autoimmune chronic active hepatitis: Human leukocyte antigens DR4 and A1-B8-DR3 are independent risk factors”, Hepatology, Vol. 13, (1991), pp 701–706. http://dx.doi.org/10.1016/0270-9139(91)92567-R[Crossref]
-  M.D.J. Strettell, P.T. Donaldson, L.J. Thomson, P.J. Santrach, S.B. Moore, A.J. Czaja and R. Williams: “Allelic basis for HLA-encoded susceptibility to type 1 autoimmune hepatitis”, Gastroenterology, Vol. 112, (1997), pp. 2028–2035. http://dx.doi.org/10.1053/gast.1997.v112.pm9178696[Crossref]
-  A. Davidson and B. Diamond: “Advances in Immunology, Autoimmune diseases”, N. Engl. J. Med., Vol. 345, (2001), pp. 340–350. http://dx.doi.org/10.1056/NEJM200108023450506[Crossref]
Publication order reference