Frequency of HLA-Class I Allel in Patients with Spondyloarthropathy

Yıl 2019, Cilt: 2 Sayı: 3, 93 - 97, 30.12.2019

Çiğdem Kekik Çınar Sonay Temurhan , Sebahat Akgül Usta , Filiz Aydın

Öz

Spondyloarthropathy (SpA) is a group of multi-systemic diseases, whose pathogenesis is not known, characterized by spinal inflammation, peripheral arthritis, and with a lower frequency by extra-articular involvement. Brevverton and Schlosstein introduced the relationship between HLA-B27 and the disease. Along with HLA-B27, the relationship of the disease with other HLA molecules was also shown in studies. Taking this information as a starting point and knowing that the disease is related to ethnic differences, we aimed to investigate the role of the HLA-A and –B alleles in Turkish patients with SpA. Typing of the patients (n=784) was performed by the complement-dependent lymphotoxicity method. The HLA-A and –B tissue groups of the control group (n: 1060) were determined by using serological or molecular methods. The frequency of HLA-B27 in patients was determined as 27%. When B27-negative patients were compared with B27-negative controls, HLA-A29 was found significantly higher in the patients (p: 0.0003, pc: 0.004). Although HLA-B60 was found significantly higher in the patients (p: 0.02), a statistical significance could not be obtained after performing the Bonferroni correction method (pc>0.05). When B27positive patients and controls were compared, HLA-A3 (p:0.0005, pc:0.008), HLA-B35 (P<0.0001, pc<0.003), HLA-B51 (P<0.0001, pc<0.003), and HLA-B52 (P<0.0001, pc:0.03) were found significantly higher in the control group, while HLA-B27 allele is related with the development of the disease. It has been shown in other studies that other HLA molecules together with ethnic differences may have an effect in liability to and protectiveness from the disease. 

Anahtar Kelimeler

HLA, Spondyloarthropaty, HLA-B27

Spondiloartropatili Hastalarda HLA Sınıf I Allel Sıklığı

Öz

Spondiloartropati (SpA), spinal inflamasyon ve periferal artrit ile daha az oranda da eklem dışı tutulumla karakterize, patogenezi henüz tam olarak bilinmeyen multisistemik bir grup hastalıktır. Genetik faktörlerin hastalığın gelişiminde önemli rolü vardır. 1973 yılında Brevverton ve Schlosstein, HLA-B27 ile hastalık ilişkisini ortaya çıkarmıştır. HLA-B27 ile birlikte diğer HLA moleküllerinin (DR1, DR4, DR8, DR15, A24, B39 ve B60)hastalıkla ilişkisi yapılan çalışmalarda gösterilmiştir. Bu bilgilerden yola çıkarak ve etnik farklılığın da hastalıkla ilişkili olduğunu düşünerek SpA’lı Türk hastalarda HLA-A ve –B allellerinin rolünü araştırmayı amaçladık.  Hastalardan (n=784) heparinli kan örneği alındı. Lenfosit izolasyonunu takiben komplemana bağımlı lenfositotoksisite yöntemi ile ticari kitler (Biotest- HLA-ABC tipleme plağı, 144X2, USA) kullanılarak tipleme yapıldı. Kontrol grubunun (n:1060) HLA-A ve –B doku grupları, serolojik veya moleküler yöntemler kullanılarak tespit edildi. Hastalarda HLA-B27 sıklığı %27 olarak saptandı. B27 negatif hastalar ile B27 negatif kontroller karşılaştırıldığında, hastalarda HLA-A29 anlamlı olarak yüksek bulundu (p:0.0003, pc:0.004, OR:2.6, CI:1.5-4.4). HLA-B60 hastalarda anlamlı olarak yüksek (p:0.02, OR:0.5, CI:0.2-0.9) bulunmasına rağmen Bonferroni doğrulama testi sonrası istatistiksel anlamlılık elde edilemedi (pc>0.05). B27 pozitif hastalarla kontrolleri karşılaştırdığımızda HLA-A3 (p:0.0005, pc:0.008, OR:0.4, CI:0.3-0.7), HLA-B35 (p<0.0001, pc<0.003, OR:0.3, CI:0.2-0.4), HLA-B51 (P<0.0001, pc<0.003, OR:0.3, CI:0.2-0.6) ve HLA-B52 (p:0.001, pc:0.03, OR:0.04, CI:0.002-0.7) kontrol grubunda, HLA-B27 (p<0.0001, pc<0.003, OR:52, CI:36.2-74.7) ise hasta grubunda anlamlı olarak yüksek bulundu. Patogenezi tam olarak bilinmeyen SpA’ların gelişiminde genetik faktörlerin rolü büyüktür. HLA-B27 allelinin hastalığın gelişimi ile ilişkili olduğu bilinmektedir. Etnik farklılıklarla birlikte diğer HLA moleküllerinin de hastalığa karşı yatkınlık ve koruyuculukta etkili olabileceği yapılan çalışmalarla gösterilmiştir.

Anahtar Kelimeler

HLA, Spondiloartropati, HLA-B27

Kaynakça

• 1. Kahn MA. HLA-B27 subtypes in world populations. Curr Opin Rheumatol 1995;7:263.
• 2. Chopra A, Raghunath D, Singh A. Spectrum of seronegative arthropathies (SSA) with special reference to HLA profiles. J Assoc Phys India 1990;38:351-5.
• 3. Lau CS, Burgos-Vargas R, Louthrenoo W, Mok MY, Wordsworth P,Zheng QY. Features of spondyloarthropathies around the world. Rheum Dis Clin North Am 1998;24:753-70.
• 4. Lopez de Castro JA. HLA-B27 and the pathogenesis of spondyloarthrapathies. Immunol Lett 2006;15:27-33.
• 5. Reveille JD, Arnett FC. Spondyloarthritis: update on pathogenesis and management. Am J Med 2005;118:592-603.
• 6. Brewerton DA, Caffrey M, Hart FD et al. Ankylosing spondylitis and HLA-B27. Lancet 1973;1:904-7.
• 7. Schlostein L, Terasaki PI, Bluestone R, Pearson CM. High association of an HLA antigen, BW27, with ankylosing spondylitis. N Engl J Med 1973;288:704-6.
• 8. Gonzales-Roces S, Alvarez MV, Gonzales S et al. HLA-B27 polymorphism and worldwide susceptibility to ankylosing spondylitis. Tissue Antigens 1997;49:116-2.
• 9. Nasution AR, Mardjuadi A, Kunmartini S, Suryadhana NG et al. HLA-B27 subtypes positively and negatively associated with spondyloarthropathy. J Rheumatol 1997;24:1111-4.
• 10. Oguz FS, Ocal L, Diler AS, Ozkul H, Asicioglu F, Kasapoglu E, Bozkurt G, Konice M, Carin M. HLA B-27 subtypes in Turkish patients with spondyloarthropathy and healthy controls. Dis Markers. 2004;20(6):309-12.
• 11. Abualrous ET, Fritzsche S, Hein Z, Al-Balushi MS, Reinink P, Boyle LH, Wellbrock U, Antoniou AN, Springer S. F pocket flexibility influences the tapasin dependence of two differentially disease-associated MHC Class I proteins. Eur J Immunol. 2015 Jan 23. doi: 10.1002/eji.201445307.
• 12. Gunal EK, Sarvan FO, Kamali S, Gul A, Inanc M, Carin M, Konice M, Aral O, Ocal L. Low frequency of HLA-B27 in ankylosing spondylitis patients from Turkey. Joint Bone Spine. 2008 May;75(3):299-302.
• 13. Toussirot E, Wendling D. Immunogenetic of ankylosing spondylitis. Rev Med Interne 2006;27:762-71.
• 14. Brown MA, Kennedy GL, Darke C, Gibson K, Pile KD, Shatford JL, et al. The effect of HLA-DR genes on susceptibility to and severity of ankylosing spondylitis. Arthritis Rheum 1998;41:460–5.
• 15. Miehle W, Schattenkirchner M, Albert D, Bunge M. HLA-DR4 in ankylosing spondylitis with different patterns of joint involvement. Ann Rheum Dis 1985;44:39–44.
• 16. Robinson WP, Van Der Linden SM, Khan MA, Rentsch HU, Cats A, Russell A, et al. HLA-Bw60 increases susceptibility to ankylosing spondylitis in HLA-B27 + patients. Arthritis Rheum 1989;32:1135–41.
• 17. De Juan MD, Reta A, Cancio J, Belzunegui J, Cuadrado E. HLA-A*9, a probable secondary susceptibility marker to ankylosing spondylitis in Basque patients. Tissue Antigens 1999;53:161–6.
• 18. Islam SM, Numaga J, Fujino Y, Masuda K, Ohda H, Hirata R, et al. HLA-DR8 and acute anterior uveitis in ankylosing spondylitis. Arthritis Rheum 1995;38:547–50.
• 19. Vargas-Alarcón G, García A, Bahena S, Melín-Aldana H, Andrade F, Ibañez-de-Kasep G, et al. HLA-B and complotypes in Mexican patients with seronegative spondyloarthropathies. Ann Rheum Dis 1994;53:755–8.
• 20. Maksymowych WP, Gorodezky C, Olivo A, Alaez C, Wong C, Burgos-Vargas R, et al. HLA-DRB1*08 influences the development of disease in Mexican mestizo with spondyloarthropathy. J Rheumatol 1997;24:904–7.
• 21. Parasannanavar DJ, Rajadhyaksha A, Ghosh K. Role of HLA-B Alleles and Clinical Presentation of B27 Negative Spondyloarthritis Patients from Mumbai, Western India. Autoimmune Dis. 2014;2014:327315. doi: 10.1155/2014/327315.
• 22. Koehler L, Kuipers JG, Zeidler H. Managing seronegative spondyloarthritis. Rheumatology 2000;39:360-8.
• 23. Prete M, Guerriero S, Dammacco R, Fatone MC, Vacca A, Dammacco F, Racanelli V. Autoimmune uveitis: a retrospective analysis of 104 patients from a tertiary reference center. J Ophthalmic Inflamm Infect. 2014 Jul 24;4:17.
• 24. Radouane A, Oudghiri M, Chakib A, Naya A, Belhouari A, El Malki A, Bennani S. HLA-B*27 allele associated to Behc¸ et’s disease and to anterior uveitis in Moroccan patients. Ann Biol Clin (Paris). 2011 JulAug;69(4):419-24.
• 25. Gustincich S, Manfiolett G, Del Sal G, Schneider C, Carninci P. A fast method for high-quality genomic DNA extraction from whole human blood. Bio Techniques 1991;11:298-302.
• 26. Olerup O, Zetterquist H. HLA-DRB1*01 subtyping by allele-specific PCR amplification: A sensitive, specific and rapid technique. Tissue Antigens 1991;37:197204.
• 27. Terasaki PI, McClelland JD. Microdroplet assay of human serum cytotoxins. Nature 1964:204;998-1000.
• 28. Şendur ÖF, Aydeniz A. Spondiloartropatilerin temel özellikleri ve ayırıcı tanı ve tedavisinin genel kriterleri. ADÜ Tıp Fakültesi Dergisi 2001:2(2);31-5.
• 29. Vargas-Alarcón G, Londono JD, Hernandez-Pacheco G, Pacheco-Tena C, Castillo E, Cardiel MH, Granados J, Burgos-Vargas R. Effect of HLA-B and HLA-DR genes on susceptibility to and severity of spondyloarthropathies in Mexican patients. Ann Rheum Dis 2002:61;714-7.
• 30. Madhavan R, Parthiban M, Panchapakesa Rajendran C, Chandrasekaran AN, Zake L, Sanjeevi B. HLA Class I and Class II association with Ankylosing spondylitis in a Southern Indian population. Ann NY Acad Sci 2002:958;403-7.
• 31. Arnais-Villena A, Carin M, Bendikuze N, GomezCasado E, Moscosa J, Oguz FS, Sarper Diler A, De Pacho A, Allende J, Guillen J, Martinez Laso J. HLA alleles and haplotypes in Turkish population: relatedness to Kurds, Armanians and other Mediterraneans. Tissue Antigens 2001:57(4);308-17.
• 32. Karahan GE, Seyhun Y, Oguz SF, Kekik C, Onal AE, Yazici H, Turkmen A, Aydin AE, Sever MS, Eldegez U, Carin MN. Impact of HLA on the underlying primary diseases in Turkish patients with end-stage renal disease. Renal Failure 2009:31;44-49.
• 33. Wei JCC, Tsai WC, Lin HS, Tsai CY, Chou CT. HLA-B60 and B61 are strongly associated with ankylosing spondylitis in HLA-B27 negative Taiwan Chinese patients. Rheumatalogy 2004:43;839-42.
• 34. Mahfoudh N, Siala M, Rihl M, Kammoun A, Frikha F, Fourati H, Younes M, Gdoura R, Gaddour L, Hakim F, Bahloul Z, Baklouti S, Bargaoui N, Sellami S , Hammami A, Makni H. Association and frequency of HLA-A, B and HLA-DR genes in south Tunisian patients with spondyloarthritis (SpA).Clin Rheumatol 2011: DOI 10.1007/s10067-011-1705-6
• 35. Pimentel-Santos FM, Matos M, Ligeiro D, Moura AF, Ribeiro C, Costa J, Santos H, Barcelos A, Pinto P, Cruz M, Sousa E, Santos RA, Fonseca JE, Trindade H, Guedes-Pinto H, Branco JC, CORPOREA Study Group. HLA alleles and HLA-B27 haplotypes associated with susceptibility and severity of ankylosing spondylitis in a Portuguese population. Tissue Antigens, 2013:82;374– 379.