Investigation of Th17 cell differentiation in immunodeficiencies associated with high IgE levels and/or autoimmunity

Year 2011, Volume: 1 Issue: 2, 96 - 102, 31.01.2014

Tunç Akkoç Ayzer Tevetoğlu İsmail Öğülür Ayşegül İzgi Elif Karakoç Aydıner Safa Barış Nerin Bahçeciler İşıl Barlan

Abstract

Objective: Hyper IgE Syndrome (HIES) and Common Variably Immunodeficiency (CVID) are immuno-deficiency diseases. HIES is characterized by recurrent skin abscesses, pneumonia, mucocutaneous fungal infections, eczama, eosinophilia and high serum IgE levels. CVID is characterized by recurrent bacterial infections in airways and gastrointestinal tract. In this study, differentiation of Th17 cells were aimed to be investigated in CVID and HIES patients.
Method: Two groups of patients diagnosed either with HIES and CVID and one group including four healty individuals were enrolled into the study. In each group, peripheral blood mononuclear cells (PBMC) and CD45RA+ naive T cells were isolated from venous blood. Isolated cells were cultured in Th17 differentiating conditions and IL-17 levels of culture supernatants were measured by ELISA method.
Results: When naive T cells obtained from HIES patients were cultured under Th17 differentiating conditions, culture supernatant IL-17 cytokine level did not show any significant increase compared to unstimulated group. When PBMCs isolated from the same patients were cultured under differentiating conditions, IL-17 cytokine level had been measured nearly statistical significant compared to healthy control group. On the other hand, when naive T cells isolated from CVID and healthy control groups were cultured under Th17 differentiating conditions, a significant increase had been observed in IL-17 levels of both groups compared to the unstimulated group. Results of differentiated cultures of isolated PBMC and naive T cells showed that there is no significant difference in the IL-17 cytokine levels between the healthy group and CVID.
Conclusion: These results show that there may be a defect in IL-17 secreting T cells in HIES group, but there is no defect in IL-17 secreting T cells in CVID patients.

Key words: HIES, CVID, immunodeficiency, Th17

Keywords

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IgE yüksekliği ve/veya otoimmünite ile seyreden immün yetmezliklerde Th17 hücre farklılaşmasının araştırılması

Abstract

Amaç: Hiper IgE Sendromu (HIES) tekrarlayan cilt apseleri, pnömoni, mukokutanöz mantar enfeksiyonları, egzema, eozinofili ve yüksek IgE düzeyi ile karakterize, Sık Değişken İmmün Yetmezlik (SDİY) ise solunum ve gastrointestinal sistemde tekrarlayan bakteriyel enfeksiyonlarla karakterize olan immün yetmezlik hastalıklarıdır. Bu çalışmada patogenezi tam olarak bilinmeyen HIES ve SDİY hastalıklarında altta yatan immünolojik bozukluğun aydınlatılması amacıyla immün yanıtta önemli olduğu bilinen Th17 hücrelerinin farklılaşmasının incelenmesi amaçlanmıştır.
Yöntem: Çalışmaya HIES ve SDİY tanısı almış iki grup hasta ve sağlıklı bireylerden oluşan bir grup kontrol alındı. Her gruptan venöz kandan Periferal Kan Mononükleer Hücreler (PKMH) ve CD45RA+ naif T hücreleri izole edildi. İzole edilen hücreler Th17 farklılaşma koşullarında kültüre edildi ve kültür süpernatantlarındaki IL-17 sitokin seviyesi ELİSA yöntemi ile ölçüldü.
Bulgular: HIES grubunda naif T hücreler Th17 farklılaştırma koşullarında kültüre edildiğinde IL-17 sitokin seviyesinde uyarım öncesine göre istatistiksel olarak anlamlı artış gözlenmedi. Aynı hasta grubundan izole edilen PMKH farklılaştırma koşullarında kültüre edildiğinde ise, IL-17 sitokin salınımı kontrol grubuna göre anlamlılığa yakın olarak düşük bulundu. SDİY ve kontrol gruplarından izole edilen naif T hücreler Th17 farklılaştırma koşullarında kültüre edildiğinde, her iki grupta da uyarım öncesine göre IL-17 sitokin seviyesinde istatistiksel olarak anlamlı artış gözlendi. İzole edilen PMKH ve naif T hücrelerin Th17 farklılaştırma kültürleri sonucu, kontrol ve SDİY grupları arasında IL-17 sitokin salınımında anlamlı fark saptanmadı.
Sonuç: Elde edilen veriler HIES’li hastalarda T hücrelerin IL-17 sitokinini üretmede kusurlu olabileceklerini, fakat SDİY’li hastalarda IL-17 üretiminde aksaklık olmadığını düşündürmüştür.

Anahtar Kelimeler : HIES, SDIY, immün yetmezlik, Th17

Keywords

HIES, SDIY, immün yetmezlik, Th17

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