Spondiloartropatili Hastalarda HLA Sınıf I Allel Sıklığı

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

Frequency of HLA-Class I Allel in Patients with Spondyloarthropathy

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. 

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