Search tips
Search criteria 


Logo of gutGutView this articleSubmit a manuscriptReceive email alertsContact usBMJ
Gut. 1992 July; 33(7): 942–946.
PMCID: PMC1379409

HLA class II genes in primary sclerosing cholangitis and chronic inflammatory bowel disease: no HLA-DRw52a association in Swedish patients with sclerosing cholangitis.


The familial predisposition to chronic inflammatory bowel disease and the increased concordance rate in monozygotic twins with Crohn's disease, suggest that genetic factors influence disease susceptibility. A 100% association with the supertypic HLA class II specificity DRw52a was recently described in white North American patients with primary sclerosing cholangitis, with or without concurrent ulcerative colitis. HLA class II alleles of the DR, DQ, and DP subregions were determined by genomic typing techniques in a large group of Swedish patients with ulcerative colitis or Crohn's disease as well as in a series of patients with primary sclerosing cholangitis. No statistically significant HLA class II association was observed in any of the investigated diseases or when the patients were subgrouped according to disease site or occurrence of extraintestinal manifestations, except an insignificant increase of the DRw17, DQw2 haplotype in patients with primary sclerosing cholangitis. The failure to confirm the well established DRw17 association in Swedish patients with sclerosing cholangitis probably represents a statistical type II error. Furthermore, this study did not verify the recently described strong DRw52a association in sclerosing cholangitis--52% of the patients were DRw52a positive compared with 28% of the controls (p less than 0.05, pc NS). This discrepancy was probably caused by different typing techniques. The DRw52a specificity was determined directly by hybridising HLA-DRB3 genes, group specifically amplified by the polymerase chain reaction, with an allele specific oligonucleotide probe, whereas in the previously mentioned study DRw52a was assigned by indirect serological criteria, which overestimate the frequency of this allele.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (993K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Prochazka EJ, Terasaki PI, Park MS, Goldstein LI, Busuttil RW. Association of primary sclerosing cholangitis with HLA-DRw52a. N Engl J Med. 1990 Jun 28;322(26):1842–1844. [PubMed]
  • Todd JA, Bell JI, McDevitt HO. HLA-DQ beta gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature. 1987 Oct 15;329(6140):599–604. [PubMed]
  • Gregersen PK, Silver J, Winchester RJ. The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum. 1987 Nov;30(11):1205–1213. [PubMed]
  • Olerup O, Smith CI, Hammarström L. Different amino acids at position 57 of the HLA-DQ beta chain associated with susceptibility and resistance to IgA deficiency. Nature. 1990 Sep 20;347(6290):289–290. [PubMed]
  • Schlosstein L, Terasaki PI, Bluestone R, Pearson CM. High association of an HL-A antigen, W27, with ankylosing spondylitis. N Engl J Med. 1973 Apr 5;288(14):704–706. [PubMed]
  • Brewerton DA, Hart FD, Nicholls A, Caffrey M, James DC, Sturrock RD. Ankylosing spondylitis and HL-A 27. Lancet. 1973 Apr 28;1(7809):904–907. [PubMed]
  • Juji T, Satake M, Honda Y, Doi Y. HLA antigens in Japanese patients with narcolepsy. All the patients were DR2 positive. Tissue Antigens. 1984 Nov;24(5):316–319. [PubMed]
  • Langdon N, Welsh KI, van Dam M, Vaughan RW, Parkes D. Genetic markers in narcolepsy. Lancet. 1984 Nov 24;2(8413):1178–1180. [PubMed]
  • Tysk C, Lindberg E, Järnerot G, Flodérus-Myrhed B. Ulcerative colitis and Crohn's disease in an unselected population of monozygotic and dizygotic twins. A study of heritability and the influence of smoking. Gut. 1988 Jul;29(7):990–996. [PMC free article] [PubMed]
  • Carlsson B, Wallin J, Böhme J, Möller E. HLA-DR-DQ haplotypes defined by restriction fragment analysis. Correlation to serology. Hum Immunol. 1987 Oct;20(2):95–113. [PubMed]
  • Bidwell J. DNA-RFLP analysis and genotyping of HLA-DR and DQ antigens. Immunol Today. 1988 Jan;9(1):18–23. [PubMed]
  • Tiercy JM, Gorski J, Jeannet M, Mach B. Identification and distribution of three serologically undetected alleles of HLA-DR by oligonucleotide.DNA typing analysis. Proc Natl Acad Sci U S A. 1988 Jan;85(1):198–202. [PubMed]
  • Fernandez-Vina M, Shumway W, Stastny P. DNA typing for class II HLA antigens with allele-specific or group-specific amplification. II. Typing for alleles of the DRw52-associated group. Hum Immunol. 1990 May;28(1):51–64. [PubMed]
  • Lanchbury JS, Hall MA, Welsh KI, Panayi GS. Sequence analysis of HLA-DR4B1 subtypes: additional first domain variability is detected by oligonucleotide hybridization and nucleotide sequencing. Hum Immunol. 1990 Feb;27(2):136–144. [PubMed]
  • Wiesner RH, LaRusso NF. Clinicopathologic features of the syndrome of primary sclerosing cholangitis. Gastroenterology. 1980 Aug;79(2):200–206. [PubMed]
  • Chapman RW, Arborgh BA, Rhodes JM, Summerfield JA, Dick R, Scheuer PJ, Sherlock S. Primary sclerosing cholangitis: a review of its clinical features, cholangiography, and hepatic histology. Gut. 1980 Oct;21(10):870–877. [PMC free article] [PubMed]
  • Evans JG, Acheson ED. An epidemiological study of ulcerative colitis and regional enteritis in the Oxford area. Gut. 1965 Aug;6(4):311–324. [PMC free article] [PubMed]
  • Farmer RG, Hawk WA, Turnbull RB., Jr Clinical patterns in Crohn's disease: a statistical study of 615 cases. Gastroenterology. 1975 Apr;68(4 Pt 1):627–635. [PubMed]
  • Olerup O, Hillert J, Fredrikson S, Olsson T, Kam-Hansen S, Möller E, Carlsson B, Wallin J. Primarily chronic progressive and relapsing/remitting multiple sclerosis: two immunogenetically distinct disease entities. Proc Natl Acad Sci U S A. 1989 Sep;86(18):7113–7117. [PubMed]
  • Hyldig-Nielsen JJ, Morling N, Odum N, Ryder LP, Platz P, Jakobsen B, Svejgaard A. Restriction fragment length polymorphism of the HLA-DP subregion and correlations to HLA-DP phenotypes. Proc Natl Acad Sci U S A. 1987 Mar;84(6):1644–1648. [PubMed]
  • Rønningen KS, Iwe T, Halstensen TS, Spurkland A, Thorsby E. The amino acid at position 57 of the HLA-DQ beta chain and susceptibility to develop insulin-dependent diabetes mellitus. Hum Immunol. 1989 Nov;26(3):215–225. [PubMed]
  • Donaldson PT, Farrant JM, Wilkinson ML, Hayllar K, Portmann BC, Williams R. Dual association of HLA DR2 and DR3 with primary sclerosing cholangitis. Hepatology. 1991 Jan;13(1):129–133. [PubMed]
  • Fujita K, Naito S, Okabe N, Yao T. Immunological studies in Crohn's disease. I. Association with HLA systems in the Japanese. J Clin Lab Immunol. 1984 Jun;14(2):99–102. [PubMed]
  • Kobayashi K, Atoh M, Yagita A, Konoeda Y, Inoko H, Ando A, Sekiguchi S. Crohn's disease in the Japanese is associated with the HLA-DRw53. Exp Clin Immunogenet. 1990;7(2):101–108. [PubMed]
  • Schrumpf E, Fausa O, Førre O, Dobloug JH, Ritland S, Thorsby E. HLA antigens and immunoregulatory T cells in ulcerative colitis associated with hepatobiliary disease. Scand J Gastroenterol. 1982 Mar;17(2):187–191. [PubMed]
  • Marsh SG, Bodmer JG. HLA-DRB nucleotide sequences, 1990. Immunogenetics. 1990;31(3):141–144. [PubMed]
  • Biemond I, Burnham WR, D'Amaro J, Langman MJ. HLA-A and -B antigens in inflammatory bowel disease. Gut. 1986 Aug;27(8):934–941. [PMC free article] [PubMed]
  • Smolen JS, Gangl A, Polterauer P, Menzel EJ, Mayr WR. HLA antigens in inflammatory bowel disease. Gastroenterology. 1982 Jan;82(1):34–38. [PubMed]
  • Katakura S, Einarsson K, Hammarström L, Smith CI. Restriction fragment length polymorphism analysis of T-cell receptor genes in inflammatory bowel disease. Scand J Gastroenterol. 1989 Apr;24(3):381–384. [PubMed]
  • Gudjonsson H, Schanfield MS, Albertini RJ, McAuliffe TL, Beeken WL, Krawitt EL. Association and linkage studies of immunoglobulin heavy chain allotypes in inflammatory bowel disease. Tissue Antigens. 1988 May;31(5):243–249. [PubMed]
  • Peña AS, Biemond I, Kuiper G, Weterman IT, van Leeuwen A, Schreuder I, van Rood JJ. HLA antigen distribution and HLA haplotype segregation in Crohn's disease. Tissue Antigens. 1980 Jul;16(1):56–61. [PubMed]
  • Modena V, Amoroso A, Frattasio C, Pera A, Costantini P, Maiocco I, Ponti V, Di Vittorio CC, Verme G, Curtoni ES. HLA antigens and clinical manifestations in Crohn's disease. Clin Exp Rheumatol. 1988 Jul-Sep;6(3):221–225. [PubMed]
  • Achord JL, Gunn CH, Jr, Jackson JF. Regional enteritis and HLA concordance in multiple siblings. Dig Dis Sci. 1982 Apr;27(4):330–332. [PubMed]
  • Colombel JF, Guillemot F, Van Gossum A, Dufossé F, Cortot A, Dupont E, Paris JC. Familial Crohn's disease in multiple siblings: no linkage to the HLA system. Gastroenterol Clin Biol. 1989 Aug-Sep;13(8-9):676–678. [PubMed]

Articles from Gut are provided here courtesy of BMJ Group