P1304 High prevalence of HLA DRB1*01:03 in Australian Inflammatory Bowel Disease patients without prediction of refractory disease
Authors: Peterson A , Zorkau I , Liu Y , Tan E T , Lee M , Moore G , Ooi J , Goldberg R 
Published: January 2025

Abstract

Background
Crohn’s disease (CD) and ulcerative colitis (UC) have been associated with the major histocompatibility complex in genome wide association studies (1) and subsequently this area is the most widely studied genetic region. HLA-DRB1*01:03 has been associated with susceptibility to both CD and UC (2), and with severe ulcerative colitis (3). However, the frequency of this allele is known to vary by ethnicity. We aimed to determine the frequency of HLA DRB1*01:03 in a multi-ethnic Australian population and determine its association with refractory disease.

Methods
At a single centre, tertiary Inflammatory Bowel Disease (IBD) service patients with either CD or UC underwent blood collection at the time of clinic appointment, endoscopy or medication infusion and their HLA DRB1 genotype was determined. Demographic and clinic data was retrospectively collected from the electronic medical record (EMR). Refractory disease was determined by failure of 1 or more advanced therapies including biologics and small molecules, as well as the use of steroids within the last 12 months. Descriptive statistics were used and a Chi Square test (IBM SPSS Version 29) used to assess the relationship between HLA DRB1*01:03 and refractory disease.

Results
123 patients were enrolled and HLA DRB1 genotypes identified. 10 patients were excluded from further analysis due to an absence of clinical data or a diagnosis of IBD-U. 113 patients were included for final analysis of which 57.5% were male, the mean age was 40.2 (+/- 16.3). 39.8% had UC and 60.2% had CD, and of those 45.5% had fistulising disease. 35.4% had previously undergone surgery and 77% of the cohort were prescribed an advanced therapy. 11.5% of patients had either heterogenous or homogenous HLA DRB1*01:03. There was no significant association between HLA DRB1*01:03 and failure of advanced therapy (P=0.88) or steroid use (P=0.88).

Conclusion
We identified a high proportion of IBD patients with HLA DRB1*01:03 compared with previous reports (4). High rates of advanced therapy use, and previous surgery indicate that the cohort has a high proportion of severe disease that could account for this finding. However, no association was found between HLA DRB1*01:03 and our measures of refractory disease possibly due to inadequate numbers in our cohort at present. Further investigation of the utility of HLA DRB1*01:03 is warranted in multi-ethnic populations.

References
1.Stokkers PCF, Reitsma PH, Tytgat GNJ, van Deventer SJH. HLA-DR and -DQ phenotypes in inflammatory bowel disease: a meta-analysis. Gut. 1999;45(3):395-401.
2.Goyette P, Boucher G, Mallon D, Ellinghaus E, Jostins L, Huang H, et al. High-density mapping of the MHC identifies a shared role for HLA-DRB1*01:03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis. Nature Genetics. 2015;47(2):172-9
3.Ahmad T, Armuzzi A, Neville M, Bunce M, Ling K-L, Welsh KI, et al. The contribution of human leucocyte antigen complex genes to disease phenotype in ulcerative colitis. Tissue Antigens. 2003;62(6):527-35.
4.Degenhardt F, Mayr G, Wendorff M, Boucher G, Ellinghaus E, Ellinghaus D, et al. Transethnic analysis of the human leukocyte antigen region for ulcerative colitis reveals not only shared but also ethnicity-specific disease associations. Human Molecular Genetics. 2021;30(5):356-69.