Publication: Chaple hastalığında düzenleyici T hücrelerin ve sitokin üretim profillerinin belirlenmesi
Abstract
Giriş: CD55 (Decay-accelaring-factor) kompleman düzenleyici bir molekül olup aynı zamanda doğal ligandı CD97 ile etkileşime girdiğinde T hücrelere uyarıcı sinyaller gönderir. CD55 eksikliğine bağlı CHAPLE hastalarında bu sinyalin kaybı immünoregulatör mekanizmalarda bozukluğa yol açabilir. Amaç: Bu çalışmada CHAPLE sendromu ve CHAPLE dışı primer intestinal lenfanjiektazi (PİL)’de lenfosit altgrupları, regulatör T hücreleri ve sitokin cevabı çalışılmıştır.Yöntem : Çalışmaya lenfosit alt grupları için15 CHAPLE, 14 Non-CHAPLE PİL ve 14 yaş uyumlu kontrol dahil edildi. Hastaların daha küçük bir grubunda sitokin kapasiteleri ölçüldü.Bulgular: CD3+T hücre, CD4+T hücre, naif-CD4+T ve naif-CD8+T hücre, MHC sınıf II ekspresyonları, RTE, exhausted CD4+T ve CD8+T hücre , NK hücre, santral hafıza-CD4+T ve efektör hafıza CD4+T hücre oranlarında non-CHAPLE PİL’lerde dikkat çekici bir dengesizlik saptandı. Sınıf dönüşümü yapmamış B hücreler de CHAPLE ve non-CHAPLE PİL hastalarında yaş uyumlu kontrollere göre farklılık saptandı. Öte yandan CHAPLE sendromunda CD21loCD38lo hücrelerde artış gözlendi. Gruplar arasında B hücreler, CD8+T hücreler, ÇNT, TCRab, TCRgd değerleri her üç grupta birbirine benzerdi. Sitokin çalışmalarında Chaple ve Non-Chaple PİL hastalarında IL-10 sağlıklı kontrollere göre anlamlı bir şekilde düşük bulundu. IFN-gamma, IL-17A, ve TNF sitokin düzeylerinde farklılık gözlenmedi. Düzenleyici T hücre oranlarında ise gruplar arası anlamlı bir farklılık saptanmadı.Sonuç: Çalışmamızda klasik olarak intestinal lenfanjiektazi ilişkili immün yetmezlik tanımında yer alan T hücre lenfopenisi ve naif CD4+T hücre düşüklüğü non-CHAPLE PİL’lerde teyid edilirken CHAPLE hastalarında bu bulguların görülmemesi iki hastalık grubunda farklı mekanistik süreçlere işaret etmektedir. Öte yandan her iki grupta IL10 üretimindeki eksiklik immün disregulasyona katkı sağlayabilir.
Background: CD55 (Decay-accelaring-factor), a famous regulator of the complement system has been shown to deliver signals through interaction with its natural ligand, CD97. Loss of this signal in CHAPLE patients due to CD55 deficiency may lead to impairment in immunoregulatory mechanisms. Aim: Herein, we studied a group patients with CHAPLE syndrome and a second group of cases with primary intestinal lymphangiectasia (PIL) with intact CD55 (non-CHAPLE- PIL). We quantified lymphocyte subgroups, regulatory T cells and cytokine responses. Materials and Methods: The study included 15 CHAPLE patients, 12 Non-CHAPLE-PILs and 14 age-matched controls (AMC). Cytokine capacities were measured in a smaller group of patients. Results : We detected a abnormalities in the percentages of CD3+T cell, CD4+T cell, naive-CD4+T and naive-CD8+T cell, MHC class II expressions, RTE , exhausted CD4+T and CD8+T cells, NK cells, central memory-CD4+T and effector memory CD4+T in the non-CHAPLE PIL group. When studying B cell subcompartments, unclass swiched memory B cell proportion was (CD19+IgD+CD27+) significantly higher in CHAPLE and non-CHAPLE PILs patients compared to AMC. On the other hand, CD21lo-CD38lo cells were increased in CHAPLE patients. All three groups had similar values for CD19+ cells, CD8+T cells, CD3+TCRab +CD4-CD8-, TCRab, and TCRgd. In cytokine studies, IL-10 was significantly lower in Chaple and Non-Chaple PIL patients compared to AMC. Whereas intracellular cytokine assessment revealed no differences in the proportion of cells producing IFN-gamma, IL-17A, or TNF. Regulatory T cell ratios were not significantly different between the groups. Conclusion: Our results recapitulate the previously characterized imune aberrations of PIL, namely, T cell lymphopenia and naïve CD4+T cell depletion, in non-CHAPLE PILs,. However, lack of these aberrations in the CHAPLE group points to different mechanistic processes in both groups. On the other hand, diminished production of IL10 in CHAPLE and non-CHAPLE PILs may be contributing to immune dysregulation.
Background: CD55 (Decay-accelaring-factor), a famous regulator of the complement system has been shown to deliver signals through interaction with its natural ligand, CD97. Loss of this signal in CHAPLE patients due to CD55 deficiency may lead to impairment in immunoregulatory mechanisms. Aim: Herein, we studied a group patients with CHAPLE syndrome and a second group of cases with primary intestinal lymphangiectasia (PIL) with intact CD55 (non-CHAPLE- PIL). We quantified lymphocyte subgroups, regulatory T cells and cytokine responses. Materials and Methods: The study included 15 CHAPLE patients, 12 Non-CHAPLE-PILs and 14 age-matched controls (AMC). Cytokine capacities were measured in a smaller group of patients. Results : We detected a abnormalities in the percentages of CD3+T cell, CD4+T cell, naive-CD4+T and naive-CD8+T cell, MHC class II expressions, RTE , exhausted CD4+T and CD8+T cells, NK cells, central memory-CD4+T and effector memory CD4+T in the non-CHAPLE PIL group. When studying B cell subcompartments, unclass swiched memory B cell proportion was (CD19+IgD+CD27+) significantly higher in CHAPLE and non-CHAPLE PILs patients compared to AMC. On the other hand, CD21lo-CD38lo cells were increased in CHAPLE patients. All three groups had similar values for CD19+ cells, CD8+T cells, CD3+TCRab +CD4-CD8-, TCRab, and TCRgd. In cytokine studies, IL-10 was significantly lower in Chaple and Non-Chaple PIL patients compared to AMC. Whereas intracellular cytokine assessment revealed no differences in the proportion of cells producing IFN-gamma, IL-17A, or TNF. Regulatory T cell ratios were not significantly different between the groups. Conclusion: Our results recapitulate the previously characterized imune aberrations of PIL, namely, T cell lymphopenia and naïve CD4+T cell depletion, in non-CHAPLE PILs,. However, lack of these aberrations in the CHAPLE group points to different mechanistic processes in both groups. On the other hand, diminished production of IL10 in CHAPLE and non-CHAPLE PILs may be contributing to immune dysregulation.