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Review article: Biomedical intelligence

Vol. 149 No. 3738 (2019)

A simple guide to the interpretation of the significance of the association of a disease with a particular HLA allele

  • Robert Winchester
DOI
https://doi.org/10.4414/smw.2019.20128
Cite this as:
Swiss Med Wkly. 2019;149:w20128
Published
12.09.2019

Abstract

This review is a simple guide to the deeper meaning of the association of a disease with a particular HLA allele. We will first review some principles of the function of the adaptive immune system, and some basic notions of autoimmune disease. In this, we will focus on the tripartite unity of the human leukocyte antigen (HLA) molecule, the peptide, and the T cell receptor that recognizes the complex of peptide and HLA molecule, placing emphasis on the function of the T cell receptor. We will also touch on the evolutionary forces shaping our adaptive immune system. Then we will apply this background to some current HLA data concerning the heterogeneity of psoriatic arthritis and the extent to which it is relayed to psoriasis, to illustrate how these principles are used to advance our understanding of the disease.

References

  1. Monos DS, Winchester R. The Major Histocompatibility Complex. In: Rich RR, ed. Clinical Immunology: Principles and Practice. 5 ed. New York, NY: Elsevier; 2018.
  2. Nair RP, Stuart PE, Nistor I, Hiremagalore R, Chia NVC, Jenisch S, et al. Sequence and haplotype analysis supports HLA-C as the psoriasis susceptibility 1 gene. Am J Hum Genet. 2006;78(5):827–51. doi:.https://doi.org/10.1086/503821
  3. Okada Y, Han B, Tsoi LC, Stuart PE, Ellinghaus E, Tejasvi T, et al. Fine mapping major histocompatibility complex associations in psoriasis and its clinical subtypes. Am J Hum Genet. 2014;95(2):162–72. doi:.https://doi.org/10.1016/j.ajhg.2014.07.002
  4. Tsoi LC, Stuart PE, Tian C, Gudjonsson JE, Das S, Zawistowski M, et al. Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants. Nat Commun. 2017;8(1):15382. doi:.https://doi.org/10.1038/ncomms15382
  5. Winchester R, Minevich G, Steshenko V, Kirby B, Kane D, Greenberg DA, et al. HLA associations reveal genetic heterogeneity in psoriatic arthritis and in the psoriasis phenotype. Arthritis Rheum. 2012;64(4):1134–44. doi:.https://doi.org/10.1002/art.33415
  6. Eder L, Chandran V, Pellet F, Shanmugarajah S, Rosen CF, Bull SB, et al. Human leucocyte antigen risk alleles for psoriatic arthritis among patients with psoriasis. Ann Rheum Dis. 2012;71(1):50–5. doi:.https://doi.org/10.1136/ard.2011.155044
  7. Vita R, Overton JA, Greenbaum JA, Ponomarenko J, Clark JD, Cantrell JR, et al. The immune epitope database (IEDB) 3.0. Nucleic Acids Res. 2015;43(Database issue):D405–12. doi:.https://doi.org/10.1093/nar/gku938
  8. Schuler MM, Nastke MD, Stevanović S. SYFPEITHI: database for searching and T-cell epitope prediction. Methods Mol Biol. 2007;409:75–93. doi:.https://doi.org/10.1007/978-1-60327-118-9_5
  9. Mobbs JI, Illing PT, Dudek NL, Brooks AG, Baker DG, Purcell AW, et al. The molecular basis for peptide repertoire selection in the human leucocyte antigen (HLA) C*06:02 molecule. J Biol Chem. 2017;292(42):17203–15. doi:.https://doi.org/10.1074/jbc.M117.806976
  10. Haroon M, Winchester R, Giles JT, Heffernan E, FitzGerald O. Certain class I HLA alleles and haplotypes implicated in susceptibility play a role in determining specific features of the psoriatic arthritis phenotype. Ann Rheum Dis. 2016;75(1):155–62. doi:.https://doi.org/10.1136/annrheumdis-2014-205461
  11. FitzGerald O, Haroon M, Giles JT, Winchester R. Concepts of pathogenesis in psoriatic arthritis: genotype determines clinical phenotype. Arthritis Res Ther. 2015;17(1):115–25. doi:.https://doi.org/10.1186/s13075-015-0640-3
  12. Winchester R, Giles J, Jadon D, Haroon M, McHugh N, FitzGerald O. Implications of the diversity of class I HLA associations in psoriatic arthritis. Clin Immunol. 2016;172:29–33. doi:.https://doi.org/10.1016/j.clim.2016.07.019
  13. Talamonti M, Botti E, Galluzzo M, Teoli M, Spallone G, Bavetta M, et al. Pharmacogenetics of psoriasis: HLA-Cw6 but not LCE3B/3C deletion nor TNFAIP3 polymorphism predisposes to clinical response to interleukin 12/23 blocker ustekinumab. Br J Dermatol. 2013;169(2):458–63. doi:.https://doi.org/10.1111/bjd.12331
  14. Dand N, Duckworth M, Baudry D, et al. HLA-C*06:02 genotype is a predictive biomarker of biologic treatment response in psoriasis. J Allergy Clin Immunol. 2019;143(6):2120–30.