Clinical Relevance of HLA-DRB1 and -DQB1 Alleles in Iranian Systemic Lupus Erythematosus Patients
HLA Alleles and Clinical Relevance in Systemic Lupus Erythematosus
Given the potential link between genetic risk factors and clinical features of systemic lupus erythematosus (SLE), this study aimed to explore the relationship between human leukocyte antigen (HLA)-DRB1/DQB1 alleles and haplotypes and clinical sub-phenotypes of the disease in a group of Iranian SLE patients.
HLA-DRB1 and HLA-DQB1 alleles were determined by PCR-SSP in 127 SLE patients and 153 ethnically-matched healthy controls. The relationships between various clinical manifestations and HLA alleles/haplotypes were analyzed in the patients.
We observed the positive associations of DRB1*07 and DRB1*07-DQB1*02 haplotypes with articular and pulmonary involvement (p=0.006 and p<0.001 respectively), DRB1*03 and DQB1*02 alleles, and DRB1*03-DQB1*02 haplotypes with cutaneous (p=0.03, p=0.004 and p=0.02 respectively) and renal involvement, and DRB1*13 as well as DRB1*13-DQB1*06 haplotypes with renal involvement. Conversely, negative associations of DRB1*13 with cutaneous and gastrointestinal disorders (p=0.004 and p=0.02 respectively) and DRB1*01 with renal involvement (p=0.03) were found in our patients. Patients carrying susceptible HLA-DRB1 alleles had a higher risk for expression of cutaneous involvement (p=0.03), anti-coagulant antibody development (p=0.01), and a lower risk for pulmonary disorders compared to patients' negatives for susceptible alleles (p=0.04).
Our findings on associations between HLA risk allele (DRB1*03) as well as non-risk alleles with particular clinical manifestations and between the potentially protective allele (DRB1*01) and protection against renal involvement indicate the important role of HLA class II genes in predisposing of specific serological and clinical features of SLE disease which could be implicative for therapeutic applications and better management of SLE patients.
2. Arbuckle MR, McClain MT, Rubertone MV, Scofield H, Dennis GJ, James JA et al. Development of auto-antibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med. 2003;49:1526–33.
3. McClain MT, Heinlen LD, Dennis GJ, Roebuck J, Harley JB, James JA. Early events in lupus humoral autoimmunity suggest initiation through molecular mimicry. Nat Med. 2005;11:85–9.
4. Morris D, Fernando M, Taylor K, Chung S, Nititham J, Alarcon-Riquelme M, et al. MHC associations with clinical and autoantibody manifestations in European SLE. Genes Immun. 2014;15(4):210-7.
5. Tang X, Huang Y, Deng W, Tang L, Weng W, Zhang X. Clinical and serologic correlations and autoantibody clusters in systemic lupus erythematosus: a retrospective review of 917 patients in South China. Medicine. 2010; 89(1):62-7.
6. Vasconcelos C, Carvalho C, Leal B, Pereira C, Bettencourt A, Costa PP, et al. HLA in Portuguese systemic lupus erythematosus patients and their relation to clinical features. Ann N Y Acad Sci. 2009;1173(1):575.
7. Wadi W. Relation between HLA typing and clinical presentations in Systemic Lupus Erythematosus patients in Al-Qassim region, Saudi Arabia. Int J Health Sci. 2014;8(2):159.
8. Niu Z, Zhang P, Tong Y. Value of HLA‐DR genotype in systemic lupus erythematosus and lupus nephritis: a meta‐analysis. Int J Rheum Dis. 2015;18(1):17-28.
9. Furukawa H, Kawasaki A, Oka S, Ito I, Shimada K, Sugii 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.
10. Pan C, Wu C, Chen H, Dang C, Chang F, Liu H, et al. Molecular analysis of HLA-DRB1 allelic associations with systemic lupus erythematous and lupus nephritis in Taiwan. Lupus. 2009;18(8):698-704.
11. Calvo-Alen J, Reveille J, Rodriguez-Valverde V, McGwin Jr G, Baethge B, Friedman A, et al. Clinical, immunogenetic and outcome features of Hispanic systemic lupus erythematosus patients of different ethnic ancestry. Lupus. 2003;12(5):377-85.
12. Teruel M, Alarcon-Riquelme ME. The genetic basis of systemic lupus erythematosus: what are the risk factors and what have we learned. J. Autoimmun. 2016;74:161–175.
13. Suurmond J, Calise J, Malkiel S, Diamond B. DNA-reactive B cells in lupus. Curr. Opin. Immunol. 2016;43:1–7.
14. Cozzani E, Drosera M, Gasparini G, Parodi A. Serology of lupus erythematosus: correlation between immunopathological features and clinical aspects. Autoimmune diseases. 2014;2014.
15. Tkachenko O, Lapin S, Maslyansky A, Myachikova V, Guseva V, Belolipetskaia E, et al. Influence of HLA-DRB1 susceptibility alleles on the autoantibodies spectrum of systemic lupus erythematosus in European part of Russia. Autoimmun Rev. 2019;18(5):558.
16. Shimane K, Kochi Y, Suzuki A, Okada Y, Ishii T, Horita T, et al. An association analysis of HLA-DRB1 with systemic lupus erythematosus and rheumatoid arthritis in a Japanese population: effects of* 09: 01 allele on disease phenotypes. Rheumatology. 2013;52(7):1172-82.
17. Bang SY, Choi JY, Park S, Choi J, Hong SJ, Lee HS, et al. Brief Report: Influence of HLA–DRB1 Susceptibility Alleles on the Clinical Subphenotypes of Systemic Lupus Erythematosus in Koreans. Arthritis Rheumatol. 2016;68(5):1190-6.
18. Galeazzi M, Sebastiani GD, Morozzi G, Carcassi C, Ferrara GB, Scorza R, et al. HLA class II DNA typing in a large series of European patients with systemic lupus erythematosus: correlations with clinical and autoantibody subsets. Medicine. 2002;81(3):169-78.
19. Aringer M, Costenbader K, Daikh D, Brinks R, Mosca M, Ramsey-Goldman R, et al. 2019 European League against Rheumatism/ American College of rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis 2019;78:1151–9.
20. Kay J, Upchurch KS. ACR/EULAR 2010 rheumatoid arthritis classification criteria. Rheumatology. 2012; 51(suppl_6):vi5-vi9.
21. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16:1215.
22. Penaranda-Parada E, Quintana G, Yunis J, Mantilla R, Rojas W, Panqueva U, et al. Clinical, serologic, and immunogenetic characterization (HLA-DRB1) of late-onset lupus erythematosus in a Colombian population. Lupus. 2015; 24(12):1293-9.
23. Arnett F, Reveille J. Genetics of systemic lupus erythematosus. Rheum Dis Clin North Am. 1992;18(4):865-92.
24. Doherty DG, Ireland R, Demaine AG, Wang F, Veerapan K, Welsh KI, et al. Major histocompatibility complex genes and susceptibility to systemic lupus erythematosus in southern Chinese. Arthritis Rheumatol. 1992;35(6):641-6.
25. Mosaad YM, Hammad A, Youssef HM, Elhanbly S. HLA-DRB1* 15 confers susceptibility to juvenile SLE but is not associated with disease presentation: an Egyptian Study. Immunol Invest. 2010;39(3):235-44.
26. Liphaus B, Kiss M, Goldberg A. HLA-DRB1 alleles in juvenile-onset systemic lupus erythematosus: renal histologic class correlations. Braz J Med Biol Res. 2007;40(4):591-7.
27. Furukawa F, Kashihara-Sawami M, Lyons MB, Norris DA. Binding of antibodies to the extractable nuclear antigens SS-A/Ro and SS-B/La is induced on the surface of human keratinocytes by ultraviolet light (UVL): implications for the pathogenesis of photosensitive cutaneous lupus. J Invest Dermatol. 1990;94(1):77-85.
28. Lundström E, Gustafsson JT, Jönsen A, Leonard D, Zickert A, Elvin K, et al. HLA-DRB1* 04/* 13 alleles are associated with vascular disease and antiphospholipid antibodies in systemic lupus erythematosus. Ann Rheum Dis. 2013;72(6):1018-25.
|Issue||Vol 20 No 1 (2021)|
|HLA-DRB1 chains HLA-DQB1 Systemic lupus erythematosus|
|Rights and permissions|
|This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.|