HLA DR4 is a marker for rapid disease progression in primary sclerosing cholangitis

Gastroenterology. 1994 Jan;106(1):160-7. doi: 10.1016/s0016-5085(94)95085-7.

Abstract

Background/aims: Primary sclerosing cholangitis (PSC) is an inflammatory disease of the biliary tree associated with an increase in the HLA alleles DR3, DR52a, DR2, Dw2, and a decrease in DR4. However, it is not certain which of these alleles provides the primary associations. Our aim was to establish the primary HLA associations with PSC and to assess the ability of HLA alleles to mark for disease progression.

Methods: By applying molecular techniques to archival tissue, we have genotyped 83 PSC patients from two populations and 131 controls for the alleles HLA DR2, DR3, DR4, DRw12, DR52a, and Dw2.

Results: HLA DR3, DR52a, DR2, and Dw2 were all significantly increased in PSC, with the relative risk for DR52a and Dw2 being greater than for DR3 and DR2, respectively. HLA DR4 was significantly decreased, but this may be artifactual to the DR3, DR2 increase. HLA DR4 and not DR52a marks for rapid disease progression in both our PSC populations.

Conclusions: HLA DR52a and Dw2 are the best candidate alleles for providing the known HLA association with PSC. HLA DR4 and not DR52a marks for rapid disease progression in our two PSC populations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigens, Differentiation / analysis
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / physiopathology
  • Base Sequence
  • Cholangitis / genetics
  • Cholangitis / immunology*
  • Cholangitis / physiopathology*
  • Chromosome Mapping
  • Chronic Disease
  • Colitis, Ulcerative / genetics
  • Colitis, Ulcerative / immunology
  • Colitis, Ulcerative / physiopathology
  • Female
  • Genotype
  • HLA-DR4 Antigen / analysis*
  • HLA-DR4 Antigen / genetics
  • Hepatitis / genetics
  • Hepatitis / immunology
  • Hepatitis / physiopathology
  • Humans
  • Leucine
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Oligonucleotide Probes / genetics
  • Polymerase Chain Reaction
  • Reference Values

Substances

  • Antigens, Differentiation
  • HLA-DR4 Antigen
  • Oligonucleotide Probes
  • Leucine