Generic placeholder image

Current Rheumatology Reviews


ISSN (Print): 1573-3971
ISSN (Online): 1875-6360

Review Article

HLAs in Autoimmune Diseases: Dependable Diagnostic Biomarkers?

Author(s): Elham Rajaei, Mohammad Taha Jalali, Saeid Shahrabi, Ali Amin Asnafi and Seyed Mohammad Sadegh Pezeshki*

Volume 15, Issue 4, 2019

Page: [269 - 276] Pages: 8

DOI: 10.2174/1573397115666190115143226

Price: $65


Background: The process of antigen presentation to immune cells is an undeniable contributor to the pathogenesis of autoimmune diseases. Different studies have indicated several factors that are related to autoimmunity. Human Leukocyte Antigens (HLAs) are among such factors, which have a key role in autoimmunity because of their involvement in antigen presentation process.

Methods: Relevant English language literature was searched and retrieved from Google Scholar search engine and PubMed database (1996-2018). The following keywords were used: "Human leukocyte antigen", "Behcet’s syndrome", "Rheumatoid arthritis", "Systemic lupus erythematosus", "Type 1 diabetes", "Celiac Disease" and "Autoimmunity".

Results: There is a strong association between HLA alleles and autoimmune diseases. For instance, HLA-B alleles and Behcet’s syndrome are strongly correlated, and systemic lupus erythematosus and Type 1 diabetes are related to HLA-DQA1 and HLA-DQB1, respectively.

Conclusion: Association between numerous HLA alleles and autoimmune diseases may justify and rationalize their use as biomarkers as well as possible diagnostic laboratory parameters.

Keywords: Human leukocyte antigen, Behcet’s syndrome, Rheumatoid arthritis, Systemic lupus erythematosus, Type 1 diabetes, Celiac disease, Autoimmunity.

Graphical Abstract
Ngo ST, Steyn FJ, McCombe PA. Gender differences in autoimmune disease. Front Neuroendocrinol 2014; 35(3): 347-69.
[] [PMID: 24793874]
Vyse TJ, Todd JA. Genetic analysis of autoimmune disease. Cell 1996; 85(3): 311-8.
[] [PMID: 8616887]
Marrack P, Kappler J, Kotzin BL. Autoimmune disease: why and where it occurs. Nat Med 2001; 7(8): 899-905.
[] [PMID: 11479621]
Mountz JD, Wu J, Cheng J, Zhou T. Autoimmune disease. A problem of defective apoptosis. Arthritis Rheum 1994; 37(10): 1415-20.
[] [PMID: 7524507]
Fernando MM, Stevens CR, Walsh EC, et al. Defining the role of the MHC in autoimmunity: a review and pooled analysis. PLoS Genet 2008; 4(4)0e1000024
[] [PMID: 18437207]
Shahsavar F, Varzi A-M, Ahmadi SAY. A genomic study on distribution of human leukocyte antigen (HLA)-A and HLA-B alleles in Lak population of Iran. Genom Data 2016; 11: 3-6.
[] [PMID: 27900264]
Bodis G, Toth V, Schwarting A. Role of Human Leukocyte Antigens (HLA) in autoimmune diseases. Rheumatol Ther 2018; 5(1): 5-20.
[] [PMID: 29516402]
Ahmadzadeh A, Saedi S, Jaseb K, Asnafi AA, Alghasi A, Saki N. T-cell acute lymphoblastic leukemia with del (7)(q11. 2q22) and aberrant expression of myeloid markers. Int J Hematol Oncol Stem Cell Res 2013; 7(4): 40-4.
[PMID: 24505542]
Asnafi AA, Jalali MT, Pezeshki SMS, Jaseb K, Saki N. The Association Between Human Leukocyte Antigens and ITP, TTP, and HIT. J Pediatr Hematol Oncol 2018.
Howell WM. HLA and disease: guilt by association. Int J Immunogenet 2014; 41(1): 1-12.
[] [PMID: 24004450]
Miyadera H, Tokunaga K. Associations of human leukocyte antigens with autoimmune diseases: challenges in identifying the mechanism. J Hum Genet 2015; 60(11): 697-702.
[] [PMID: 26290149]
Davatchi F, Chams-Davatchi C, Shams H, et al. Adult Behcet’s disease in Iran: analysis of 6075 patients. Int J Rheum Dis 2016; 19(1): 95-103.
[] [PMID: 26258691]
Ryu HJ, Seo MR, Choi HJ, Baek HJ. Clinical phenotypes of Korean patients with Behcet disease according to gender, age at onset, and HLA-B51. Korean J Intern Med (Korean Assoc Intern Med) 2017.
[] [PMID: 28073242]
Kurata R, Yonezawa T, Inoko H. Association Analysis of the Polymorphism of Human Leuko-cyte Antigen-A,-B and-E Gene with Behcet’s Disease in Japa-nese Cohort Using Sequencing-Based Typing Method. MOJ Immunol 2014; 1(3): 00013.
Hughes T, Coit P, Adler A, et al. Identification of multiple independent susceptibility loci in the HLA region in Behçet’s disease. Nat Genet 2013; 45(3): 319-24.
[] [PMID: 23396137]
Park KS, Park JS, Nam JH, Bang D, Sohn S, Lee ES. HLA-E*0101 and HLA-G*010101 reduce the risk of Behcet’s disease. Tissue Antigens 2007; 69(2): 139-44.
[] [PMID: 17257316]
Ombrello MJ, Kirino Y, de Bakker PI, Gül A, Kastner DL, Remmers EF. Behçet disease-associated MHC class I residues implicate antigen binding and regulation of cell-mediated cytotoxicity. Proc Natl Acad Sci USA 2014; 111(24): 8867-72.
[] [PMID: 24821759]
Pfeifle R, Rothe T, Ipseiz N, et al. Regulation of autoantibody activity by the IL-23-TH17 axis determines the onset of autoimmune disease. Nat Immunol 2017; 18(1): 104-13.
[] [PMID: 27820809]
Lerner A, Matthias T. Rheumatoid arthritis-celiac disease relationship: joints get that gut feeling. Autoimmun Rev 2015; 14(11): 1038-47.
[] [PMID: 26190704]
Yang Z, Matteson EL, Goronzy JJ, Weyand CM. T-cell metabolism in autoimmune disease. Arthritis Res Ther 2015; 17(1): 29.
[] [PMID: 25890351]
Karlson EW, Chibnik LB, Cui J, et al. Associations between human leukocyte antigen, PTPN22, CTLA4 genotypes and rheumatoid arthritis phenotypes of autoantibody status, age at diagnosis and erosions in a large cohort study. Ann Rheum Dis 2008; 67(3): 358-63.
[] [PMID: 17666451]
Jawaheer D, Li W, Graham RR, et al. Dissecting the genetic complexity of the association between human leukocyte antigens and rheumatoid arthritis. Am J Hum Genet 2002; 71(3): 585-94.
[] [PMID: 12181776]
Gonzalez-Gay MA, Garcia-Porrua C, Hajeer AH, Eds. Influence of human leukocyte antigen-DRB1 on the susceptibility and severity of rheumatoid arthritis seminars in arthritis and rheumatism. Elsevier 2002.
Furukawa H, Oka S, Shimada K, Hashimoto A, Tohma S. Human leukocyte antigen polymorphisms and personalized medicine for rheumatoid arthritis. J Hum Genet 2015; 60(11): 691-6.
[] [PMID: 25903069]
Tsao BP. The genetics of human systemic lupus erythematosus. Trends Immunol 2003; 24(11): 595-602.
[] [PMID: 14596884]
Ghodke-Puranik Y, Niewold TB. Immunogenetics of systemic lupus erythematosus: A comprehensive review. J Autoimmun 2015; 64: 125-36.
[] [PMID: 26324017]
Dedhia L, Pradhan V, Ghosh K, Nadkar M, Parekh S. Association of Human Leucocyte Antigen (HLA) class II with Systemic Lupus Erythematosis (SLE) patients from western India. Meta Gene 2018.
Gambino CM, Di Bona D, Aiello A, et al. HLA-C1 ligands are associated with increased susceptibility to systemic lupus erythematosus. Hum Immunol 2018; 79(3): 172-7.
[] [PMID: 29395276]
Furukawa H, Kawasaki A, Oka S, et al. Human leukocyte antigens and systemic lupus erythematosus: a protective role for the HLA-DR6 alleles DRB1*13:02 and *14:03. PLoS One 2014; 9(2)e87792
[] [PMID: 24498373]
Morris DL, Fernando MM, Taylor KE, et al. Systemic lupus erythematosus genetics consortium. MHC associations with clinical and autoantibody manifestations in European SLE. Genes Immun 2014; 15(4): 210-7.
[] [PMID: 24598797]
Cruz GI, Shao X, Quach H, et al. A Child’s HLA-DRB1 genotype increases maternal risk of systemic lupus erythematosus. J Autoimmun 2016; 74: 201-7.
[] [PMID: 27388144]
Rosado S, Perez-Chacon G, Mellor-Pita S, et al. Expression of human leukocyte antigen-G in systemic lupus erythematosus. Hum Immunol 2008; 69(1): 9-15.
[] [PMID: 18295670]
Yasunaga S, Kimura A, Hamaguchi K, Rønningen KS, Sasazuki T. Different contribution of HLA-DR and -DQ genes in susceptibility and resistance to insulin-dependent diabetes mellitus (IDDM). Tissue Antigens 1996; 47(1): 37-48.
[] [PMID: 8929711]
Valdes AM, Erlich HA, Noble JA. Human leukocyte antigen class I B and C loci contribute to Type 1 Diabetes (T1D) susceptibility and age at T1D onset. Hum Immunol 2005; 66(3): 301-13.
[] [PMID: 15784469]
Skog O, Korsgren S, Wiberg A, et al. Expression of human leukocyte antigen class I in endocrine and exocrine pancreatic tissue at onset of type 1 diabetes. Am J Pathol 2015; 185(1): 129-38.
[] [PMID: 25524212]
Lavant EH, Carlson JA. A new automated human leukocyte antigen genotyping strategy to identify DR-DQ risk alleles for celiac disease and type 1 diabetes mellitus. Clin Chem Lab Med 2009; 47(12): 1489-95.
[] [PMID: 19929553]
Ooi JD, Petersen J, Tan YH, et al. Dominant protection from HLA-linked autoimmunity by antigen-specific regulatory T cells. Nature 2017; 545(7653): 243-7.
[] [PMID: 28467828]
Cavalli G, Hayashi M, Jin Y, et al. MHC class II super-enhancer increases surface expression of HLA-DR and HLA-DQ and affects cytokine production in autoimmune vitiligo. Proc Natl Acad Sci USA 2016; 113(5): 1363-8.
[] [PMID: 26787888]
Terao C, Yoshifuji H, Matsumura T, Naruse TK, Ishii T, Nakaoka Y, et al. Genetic determinants and an epistasis of LILRA3 and HLA-B* 52 in Takayasu arteritis. Proceedings of the National Academy of Sciences. 201808850
[] [PMID: 30498034]
van Gerven NM, de Boer YS, Zwiers A, et al. Dutch Autoimmune Hepatitis Study Group. HLA-DRB1*03:01 and HLA-DRB1*04:01 modify the presentation and outcome in autoimmune hepatitis type-1. Genes Immun 2015; 16(4): 247-52.
[] [PMID: 25611558]
Lee HJ, Li CW, Hammerstad SS, Stefan M, Tomer Y. Immunogenetics of autoimmune thyroid diseases: A comprehensive review. J Autoimmun 2015; 64: 82-90.
[] [PMID: 26235382]
Antonelli A, Ferrari SM, Corrado A, Di Domenicantonio A, Fallahi P. Autoimmune thyroid disorders. Autoimmun Rev 2015; 14(2): 174-80.
[] [PMID: 25461470]
Ramgopal S, Rathika C, Malini RP, Murali V, Arun K, Balakrishnan K. Critical amino acid variations in HLA-DQB1* molecules confers susceptibility to autoimmune thyroid disease in south India. Genes Immun 2018; 1.
[] [PMID: 29307887]
Fallahi P, Ferrari SM, Ruffilli I, et al. The association of other autoimmune diseases in patients with autoimmune thyroiditis: Review of the literature and report of a large series of patients. Autoimmun Rev 2016; 15(12): 1125-8.
[] [PMID: 27639841]
Carbone F, De Rosa V, Carrieri PB, et al. Regulatory T cell proliferative potential is impaired in human autoimmune disease. Nat Med 2014; 20(1): 69-74.
[] [PMID: 24317118]
Hayes CE, Hubler SL, Moore JR, Barta LE, Praska CE, Nashold FE. Vitamin D actions on CD4+ T cells in autoimmune disease. Front Immunol 2015; 6: 100.
[] [PMID: 25852682]
Gul A. Behcet's disease: an update on the pathogenesis. Clinical and experimental rheumatology 2001; 19 (5; SUPP/24): S-6.
[PMID: 11760403]
Fourlanos S, Varney MD, Tait BD, et al. The rising incidence of type 1 diabetes is accounted for by cases with lower-risk human leukocyte antigen genotypes. Diabetes Care 2008; 31(8): 1546-9.
[] [PMID: 18487476]
Delong T, Wiles TA, Baker RL, et al. Pathogenic CD4 T cells in type 1 diabetes recognize epitopes formed by peptide fusion. Science 2016; 351(6274): 711-4.
[] [PMID: 26912858]
Mok CC, Lau CS. Pathogenesis of systemic lupus erythematosus. J Clin Pathol 2003; 56(7): 481-90.
[] [PMID: 12835292]
Pineton de Chambrun M, Wechsler B, Geri G, Cacoub P, Saadoun D. New insights into the pathogenesis of Behçet’s disease. Autoimmun Rev 2012; 11(10): 687-98.
[] [PMID: 22197900]

Rights & Permissions Print Export Cite as
© 2024 Bentham Science Publishers | Privacy Policy