Behçet Hastalığı Patogenezinde 21-Hidroksilaz Eksikliğinin Rolü

Amaç: Akne benzeri deri lezyonlarının sıklığı ve hastalığın erkeklerde daha ağır seyretmesi Behçet hastalığı (BH) patogenezinde seks hormonlarının rolünün olabileceğini düşündürmektedir. HLA-B51 BH için en önemli genetik duyarlılık faktörüdür. Konjenital adrenal hiperplazilerin (KAH) çoğundan sorumlu olan CYP21A2 geni kromozom 6p21.3’deki MHC bölgesinde yerleşimlidir. Bu çalışmada CYP21A2 genindeki olası bazı mutasyonların HLA-B51 ile bağlantı dengesizliği göstererek 21-hidroksilaz eksikliğine ve bunun sonucunda androjen fazlalığına yol açarak BH patogenezine katkı yapabileceği hipotezini araştırmayı amaçladık.Gereç ve Yöntem: Çalışma grubunu 18 sağlıklı kontrol, 29 BH olan hasta ve 15 ankilozan spondilit (AS) hastası oluşturdu. Bütün hastalara ACTH uyarı testi yapıldı. Bazal ve ACTH uyarısı sonrası serum kortizol ve 17-OH-progesteron (17-OH-P) düzeyleri ve bazal dehidroepiandrosteron sülfat (DHEA-S), total testosteron ve seks hormonu bağlayıcı globulin (SHBG) düzeyleri ölçüldü.Bulgular: Kılavuzların önerdiği şekilde, klasik olmayan KAH tanısı için 17-OH-P için eşik değer olarak 10 ng/mL alındı. ACTH uyarısı sonrası 3 BH (%10,3) ve 5 AS hastasının (%33,3) 17-OH-P düzeyleri yüksek bulundu. Bu hastaların klasik olmayan KAH hastaları ya da KAH mutasyonları için taşıyıcı olabileceği düşünüldü. Belirgin aknesi olan 8 BH’dan üçünün biyokimyasal değerleri klasik olmayan KAH ile uyumluydu. BH olanların ortalama total testosteron düzeylerinin sağlıklı kontrollerinkinden anlamlı olarak düşük olduğu görüldü. Bununla birlikte 17-OH-P düzeyi yüksek olan hastalarda testosteron düzeyleri normaldi. Sonuç: Bu pilot çalışmada BH ve AS hastalarının bir grubunda ACTH uyarısı sonrası yüksek 17-OH-P değerleri gözlemledik. Bulgularımız HLA-B allelleri ile bağlantı dengesizliği gösteren olası 21-hidroksilaz eksikliğinin patogeneze katkısının olabileceğini düşündürmekte ve verilerin genetik çalışmalarla doğrulanmasını gerektirmektedir.

Anahtar Kelimeler:

21-hidroksilaz eksikliği, Behçet hastalığı, Ankilozan spondilit, HLA-B51, HLA-B27, CYP21A2 geni

The Role of 21-Hydroxylase Deficiency in The Pathogenesis of Behçet Disease

Objective: Acne-like skin lesions and more severe disease course in males suggest a role for sex hormones in the pathogenesis of Behçet disease (BD). HLA-B51 is the main genetic susceptibility factor for BD, and CYP21A2 gene responsible for most of congenital adrenal hyperplasia (CAH) is located within the MHC locus on chromosome 6p21.3. We aimed to investigate the possible role of 21-hydroxylase deficiency in linkage disequilibrium with HLA-B51 and causing androgen excess.Materials and Methods: We studied 18 healthy controls, 29 BD patients and 15 patients with ankylosing spondylitis (AS). All subjects underwent ACTH stimulation test. Basal and stimulated serum cortisol and 17-OH-progesterone (17-OH-P) levels and basal dehydroepiandrosterone sulfate (DHEA-S), total testosterone and sex hormone binding globulin (SHBG) levels were measured.Results: According to current guidelines, we accepted 10 ng/mL as the cut-off point for 17-OH-P to define non-classic CAH (NCAH). After ACTH stimulation 3 of BD patients (10.3%) and 5 AS patients (33.3%) had high 17-OH-P concentrations. Those individuals were considered as NCAH or possible carriers for CAH mutations. Three out of 8 BD patients with prominent acne were identified as NCAH biochemically. Mean total testosterone levels of BD patients were significantly lower than those of healthy controls, however these levels were normal in BD patients with high 17-OH-P. Conclusion: This preliminary work documented high 17-OH-P levels following ACTH stimulation in a subset of BD and AS patients, and genetic studies are necessary to investigate the role of 21-hydroxylase deficiency in association with HLA-B alleles in their pathogenesis.

Keywords:

21-hydroxylase deficiency, Behçet disease, Ankylosing spondylitis, HLA-B51, HLA-B27, CYP21A2 gene,

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