Association of HLA-DRB1 alleles and autoimmune hepatitis in Turkish patients

Amaç: Otoimmun hepatit (OIH), dolaşımdaki otoantikorlar ve yüksek serum globulin düzeyiyle birlikte seyreden, nedeni bilinmeyen kronik bir nekroinflamatuar karaciğer hastalığıdır. İmmünogenetik çalışmalarda, otoimmunite ile HLA (Human Leukocyte Antigen) antijenleri arasında ilişki bulunmuş olup, lenfositlerin yüzeyinde bulunan HLA antijeninde azalma ve HLA tarafından düzenlenen genlerin ekspresyonunda bozulma saptanmıştır. Yapılan çalışmalarda otoimmun hepatit ile HLA-DRB1*03, *04, *13 antijenleri arasında anlamlı birliktelikler bulunmuştur. Bu çalışmada otoimmun hepatit ile HLA-DRB1 antijenleri arasındaki ilişki araştırılmıştır. Hastalar ve Yöntemler: Çalışmamıza 113 hasta (55 kadın, 58 erkek; ort. yaş 44.8±21.21; dağılım 10-82) ve otoimmun hastalığı olmayan 300 sağlıklı birey (198 kadın, 102 erkek; ort. yaş 32.4±10.48; dağılım 17-50) dahil edilmiştir. Standart yöntemler ile DNA izolasyonu yapıldıktan sonra PCR-SSP yöntemi ile HLA-DRB1 doku tiplendirmesi yapılmıştır. Elde edilen sonuçlar Fisher's exact testi kullanılarak değerlendirilmiştir. Bulgular: Hasta grubunda DRB1*03 alel sıklığının kontrol grubuna oranla yüksek bulunurken DRB1*13 aleli ise kontrole göre anlamı olarak düşük sıklıkta olduğu görülmüştür. Sonuç: HLA-DRB1*03 alelinin hastalığa yatkınlığı HLA-DRB1*13 alelinin ise hastalığa karşı koruyucu özellikte olduğu düşünülmektedir.

Otoimmün hepatit ile HLA-DRB1 alel ilişkisi

Objectives: Autoimmune hepatitis (AIH) which is characterized by hypergammaglobulinemia and a wide range of circulating auto antibodies is a necroinflammatory liver disease of unknown aetiology. Immunogenetic studies have shown the association of autoimmunity with HLA (Human Leukocyte Antigen) alleles. Furthermore, they have shown a decrease in the expression of HLA antigens on lymphocyte surface and a dysregulation of gene expression arranged by HLA. A significant association is found between AIH and HLA-DRB1*03, *04 and *13 alleles in various studies. We performed HLA-DRB1 genotyping in Turkish patients with AIH. Patients and Methods: The study group consisted of 113 patients (55 females, 58 males; mean age 44.8±21.21; range 10-82) with AIH and 300 healthy individuals (198 females, 102 males; mean age 32.4±10.48; range 17-50). After DNA isolation by standard methods, HLA-DRB1 typing was performed by using polymerase chain reaction amplification with sequence-specific primers (PCR-SSP). Results: HLA-DRB1*03 allele had a significantly increased frequency in the patient group. On the other hand, DRB1*13 allele had a significantly decreased frequency compared with the healthy controls. Conclusion: HLA-DRB1*03 might play a role in the pathogenesis of AIH while HLA-DRB1*13 might have a protective role for AIH.

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