İmatinib Tedavisi Alan Hastalarda T Lenfosit Aktivasyonunun Akım Sitometrik Analizi

Yıl 2020, , 180 - 187, 17.03.2020

Deniz Goren Sahin , Klara Dalva Sema Meriç Günhan Gürman Muhit Özcan Önder Arslan Mutlu Arat

https://doi.org/10.20515/otd.532364

Öz

İmatinibin in vivo ortamda T lenfosit
fonksiyonları üzerine olan etkileri akım sitometrik olarak
değerlendirilmiştir.  Çalışmaya toplam 29 KML hastası ve 9 sağlıklı birey
dahil edilmiştir. KML hastaları kendi aralarında sırasıyla, yeni tanı almış ve
tedavi görmeyen, 1 yıldır imatinib alan ve 1 yıldan uzun süredir imatinib alan
hastalar olarak 3 gruba ayrılmıştır. CD4+ hücreler ve bu hücrelerdeki IL-4
ve IFNg ifadeleri, CD3+ T lenfositlerin % kaçının aktive edilmiş olduğu
(CD3+CD69+), CD8+ hücreler ve bu hücrelerde HLA-ABC ve HLA-DR ifade eden
hücrelerin oranı ve HLA-ABC ve HLA-DR ifadelerinin şiddeti değerlendirilmiştir. Gruplar arasında ortalama CD4 + hücre
sayısı açısından anlamlı fark yoktu. Bununla birlikte, kontrol grubunda daha
yüksek CD4 + hücrelerine doğru bir eğilim vardı. IL-4 ve IFN gama, gruplar
arasında istatistiksel olarak anlamlı bulunmadı. Kontrol grubu daha düşük IL-4
ve IFN gama ifade değerlerine sahipti. IL-4 ve IFN gama ifade etmeyen ortalama
CD4 + hücre sayısı kontrol grubunda diğer gruplara göre istatistiksel olarak
daha yüksekti. Kontrol grubunda ise % aktivasyon diğer gruplara göre azdı. Tüm
hasta gruplarında CD8 + hücre oranı istatistiksel olarak daha düşük bulundu (p
= 0,001). HLA-ABC ve HLA-DR'nin CD8 + hücrelerinde ekspresyonu gruplar arasında
benzerdi. İmatinibin sitokin sentezi üzerine herhangi bir etkisi
gözlenmemiştir. İmatinib tedavisi altındaki hastalarda T lenfosit
fonksiyonlarının etkilendiğine dair klinik belirgin gözlemler olmamakla
birlikte, subklinik etki varlığı araştırma konusudur. Yapılan in vitro çalışmaların in-vivo
korele olup olmadığının aydınlatılabilmesi için daha ileri çalışmalara
gereksinim vardır. 

Anahtar Kelimeler

kronik miyelositer lösemi, akım sitometri, imatinib, T hücre

Flow Cytometric Analysis of T Lymphocyte Activation in CML Patients Under Imatinib Therapy

Öz

To analyze
T cell functions by flow cytometry and to evaluate the possible functional
changes that might occur under imatinib therapy in CML patients. A total of 29
patients and 9 healthy control subjects were enrolled. Newly diagnosed patients
having no treatment (group 1), patients receiving imatinib for 1 year (group 2)
and patients receiving imatinib more than 1 year (group 3), healthy control
subjects (group 4). IL-4 and IFN gamma expression on CD4+ cells; how much
percentage of CD3+ T cells were activated (CD3+CD69+); CD8+ T cells and the
ratio and grade of expression of HLA-ABC and HLA-DR on those cells were
evaluated, respectively.

There was
no significant difference in terms of mean number of CD4+ cells between the
groups. However, there was a tendency towards higher CD4+ cells in control
group. IL-4 and IFN gamma were found not to be statistically significant
between the groups. Control group has lower IL-4 and IFN gamma expression
values. Mean number of CD4+ cells, which did not express IL-4 and IFN gamma,
were statistically higher in control group when compared to other groups. In
control group, % activation was decreased when compared to that of other
groups. CD8+ cell ratio was found to be statistically lower in all patient
groups (p=0.001). The expression of HLA-ABC and HLA-DR on CD8+ cells were
similar between the groups. We could not show any inhibitory effect of imatinib
on T cell functions in concordance with clinical experience and safety profile. 

Anahtar Kelimeler

chronic myelogenous leukemia, flow cytometry, imatinib, T cell

Kaynakça

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