HLAB27 and HLADRB1 Genotyping of Spondyloarthropathies among Filipino Patients


Objective: To investigate the role of HLA genes among Filipino patients of varying ages with spondyloarthropathies compared to healthy controls in a tertiary center.

Methods: This is a case-control study where the index patient is matched by a related and unrelated control. HLA-B27 and HLA-DRB1 genotyping were performed via polymerase chain reaction using sequence specific primers

Results: There were 47 index patients, mean age of 39.38 years, 22 females and 25 males. Of these, 25 had psoriatic arthritis (PsA), 19 ankylosing spondylitis (AS), 2 undifferentiated arthritis (UA), 1 inflammatory bowel disease (IBD). More females (64%) had PsA while more males (84%) had AS. HLAB-27 was identified in 22 patients. Among these, 17 were AS patients, 3 PsA, 2 UA, no IBD. HLAB27 was significantly associated with axial involvement (OR= 14, 95% CI3.38,58.07) and bilateral sacroiliitis (OR= 16.61, 95%CI 3.11,88.8), but not with peripheral involvement (OR=0.125, 95%CI 0.32, 0.485) (p<0.05). Of the HLAB27 + AS patients, 16 had axial symptoms, 14 had bilateral while 3 had unilateral sacroiliitis, 3 had uveitis. Of the HLAB27+ PsA patients, 2 have prominent axial involvement, while 3 patients with axial involvement were HLAB27 -. No pattern of DRB1 alleles was found to be significantly associated with any of the spondyloarthropathies.

Conclusion: This first genetic study on genetic polymorphism among Filipino patients strengthened the association of HLAB27 with AS. However, there was no pattern of association with HLADRB1 alleles in this cohort of patients.

This is the first study that confirms a significant HLAB27 susceptibility of Filipino spondyloarthropathy patients. However, exploratory findings did not find a HLADRB1 genotype to extend a similar susceptibility pattern.

  1. Van der Linden SM, Valkenburg HA, De Jongh BM, Cats A. The risk of developing ankylosing spondylitis in HLA-B27 positive individuals. A comparison of relatives of spondylitis patients with the general population. Arthritis Rheum 1984;27(3):241–9. Available from: doi: 10.1002/art.1780270301
  2. Taurog JD. The mystery of HLAB27: If it isn’t one thing, it’s another. Arthritis Rheum 2007;56(8):2478-2481. Available from: doi: 10.1002/art.22807
  3. Said-Nahal R, Miceli-Richard C, Gautreau C, Tamouza R, Borot N, Porcher R, et.al. The role of HLA genes in familial spondyloarthropathy: a comprehensive study of 70 multiplex families. Ann Rheum Dis 2002;61(3):201–206. Available from: http://dx.doi.org/10.1136/ard.61.3.201
  4. Vargas-Alarcon G, Londono JD, Hernandez-Pacheco G, Pacheco-Tena C, Castillo E, Cardiel MH, et.al. Effect of HLA-B and HLA-DR genes on susceptibility to and severity of spondyloarthropathies in Mexican Patients. Ann Rheum Dis 2002;61(8):714-717. Available from: http://dx.doi.org/10.1136/ard.61.8.714
  5. Khan MA. Update: the twenty subtypes of HLA-B27. CurrOpinRheumatol 2000;.12(4):235– 238.
  6. Feltkamp TEW, Mardjuadi A, Huang F, Chou CT. Spondyloarthropathies in eastern Asia. Cur Opin Rheumatology 2001;13(4):285–290.
  7. Cauli A, Vacca A, Mameli A, Passiu G, Fiorillo MT, Sorrentino R, et.al. A Sardinian patient with ankylosing spondylitis and HLA–B*2709 co‐occurring with HLAB*1403. Arthritis Rheum 2007;56(8):2807–2809. Available from: doi: 10.1002/art.22819
  8. Haroon N, Tsui FW, Uchanska-Ziegler B, Ziegler A, Inman RD. Endoplasmic reticulum aminopeptidase 1 (ERAP1) exhibits functionally significant interaction with HLA-B27 and relates to subtype specificity in ankylosing spondylitis. Ann Rheum Dis 2012;71(4):589–595. Available from: http://dx.doi.org/10.1136/annrheumdis-2011-200347.
  9. Sheehan NJ. HLA-B27: What’s New? Rheumatology 2010;49(4):621–631. Available from: https://doi.org/10.1093/rheumatology/kep450.
  10. Tuokko J, Reijonen H, Ilonen J, Anttila K, Nikkari S, Mottonen T, et.al. Increase of HLA-DRB1*0408 and -DQB1*0301 in HLAB27 positive reactive arthritis. Ann Rheum Dis 1997;56(1):37-40. Available from: http://dx.doi.org/10.1136/ard.56.1.37
  11. Mahfoudh N, Siala M, Rihl M, Kammoun A, Frikha F, Fourati H, et.al. Association and frequency of HLA-A, B and HLA-DR genes in south Tunisian patientswithspondyloarthritis (SpA). Clinical Rheumatology 2011;30:1069–1073.
  12. Komata T, Tsuchiya N, Hatta Y, Matsushita M, Ogawa A, Mitsui H, et.al. HLA-DRB1 alleles encoding the shared epitope associated with rheumatoid arthritis confer additionalsusceptibility to seronegativespondyloarthropathies in HLA-B27 positive Japanese individuals. Modern Rheumatol 1999;9(1):55-64. Available from: doi:10.1007/BF03041259
  13. Eder L, Chandran V, Pellett F, Shanmugarajah S, Rosen CF, Bull SB, et.al. Differential human leucocyte allele association between psoriasis and psoriatic arthritis: a family based association study. Ann Rheum Dis 2012;71(8):1361-1365.Available from: http://dx.doi.org/10.1136/annrheumdis-2012-201308
  14. Braun J, Bollow M, Reminger G, Eggens U, Rudwaleit M, Distler A, et.al. Prevalence of spondyloarthropathies in HLAB27 positive and negative blood donors. Arthritis Rheum 1998;41(1):58-67. Available from: 10.1002/1529-0131(199801)41:1<58::AID-ART8>3.0.CO;2-G
  15. Chung HY, Machado P, van der Heijde D, D'Agostino MA, Dougados M. HLAB-27 positive patients differ from HLAB27 negative patients in clinical presentation and imaging: results from the DESIR cohort of patients with recent onset axial spondyloarthritis. Ann Rheum Dis 2011;70(11):1930-36. Available from:http://dx.doi.org/10.1136/ard.2011.152975.
  16. Zeboulon N, Dougados M, Gossec L. Prevalence and characteristics of uveitis in the spondyloarthropathies: a systematic literature review. Ann Rheum Dis 2008;67(7):955-959. Available from:http://dx.doi.org/10.1136/ard.2007.075754.
  17. Wu Z, Mou Y, Lin Z, Huang J, Wei Q, Gu J. HLAB27 polymorphism in Han Chinese patients with ankylosing spondylitis: a distinctive disease association for B*2715 in a multiplex family. J Rheumatol 2009;36(12):2849-2850. Available from: https://doi.org/10.3899/jrheum.090341
  18. Gladman DD, Farewell VT, Kopciuk K, Cook RJ. HLA antigens and progression in psoriatic arthritis. J Rheumatol 1998;25:730-3.
  19. Bhalero J, BowcockAM. The genetics of psoriasis: a complex disorder of the skin and the immune system. Hum Mol Genet 1998;7(10):1537-45. Available from: http://doi.org/10.1093/hmg/7.10.1537.
  20. Gladman DD, Farewell VT, Rahman P, Schentag CT, Pellett F, Ng CM, et al. HLA-DRB1*04 alleles in psoriatic arthritis: comparison with rheumatoid arthritis and healthy controls. Human Immunol 2001;62(11):1239-1244. Available from: https://doi.org/10.1016/S0198-8859(01)00337-8

Articles related to the one you are viewing

There are currently no results to show, please try again later

CC BY: Open Access Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/