IC-04. Comparison of different T-helper cell populations in patients with and without chronic graft-versus-host disease after allo-HSCT for acute leukemia
Olga S. Starikova, Mikhail Y. Drokov, Nikolai M. Kapranov, Irina V. Galtseva, Ekaterina G. Khamaganova, Ksenia A. Nikiforova, Yulia O. Davydova, Vera A. Vasilyeva, Ekaterina D. Mikhaltsova, Natalia N. Popova, Daria S. Dubnyak, Anna A. Dmitrova, Olga M. Koroleva, Zoya V. Konova, Mobil I. Akhmedov, Maria V. Dovydenko, Uliana V. Maslikova, Feruza A. Omarova, Elmira I. Kolgaeva, Mironova D.A., Inara S. Saidullaeva, Luiza A. Karaseva, Larisa A. Kuzmina, Elena N. Parovichnikova,
National Research Center for Hematology, Moscow, Russia
Contact: Dr. Mikhail Y. Drokov, e-mail: firstname.lastname@example.org
Chronic GVHD (cGVHD) is one of the most common late complications of allo-HSCT that affects relapse-free survival rates and quality of life in the patients. T-helper cells (Th) play one of the key roles in the pathogenesis of cGVHD. Our objective was to compare the amounts of Th cell subpopulations in peripheral blood (PB) of the patients with cGVHD and those without this complication at +180 days after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Materials and methods
49 patients who underwent allo-HSCT for acute leukemia (27 AML, 22 ALL) were included into the study. Their median age is 40 years (20 to 58). Allo-HSCT was performed from related haploidentical donor in 32 patients (65%), the rest, others received grafts from compatible unrelated donors. cGVHD was developed in 18 (37%) patients. PB samples were taken at the day +180 after allo-HSCT and were analyzed by multicolor flow cytometry by means of “CytoFLEX” device (Beckman Coulter). As based on expression of CD25, CD3, CD4, CD8, CXCR3, CCR6, CCR4, CCR10, CXCR3, CXCR5, the following cell populations have been identified: Th type 1 (Th1), Th type 2, Th type 17, Th22 type (Th22), T-follicular helpers, T-regulatory cells. When measuring expression of CD45RA, CCR7 and CD45RA, these populations were discerned according to their degree of maturation, e.g., naive cells, central memory (CM) cells, transient memory, effector memory (EM) and terminally differentiated cells.
On day +180 after allo-HSCT, blood samples from the patients suffering from cGVHD contained significantly higher absolute counts of Th cells (in cGVHD cases, 104 cells/μl; in cGVHD-free patients, 62 cells/μl, p=0.005), as well as Th1 CM-phenotype (in cGVHD patients, 1.91 cells/μl; without cGVHD, 0.88 cells/μl, p=0.021), and Tx22 CM cell phenotype (in cGVHD, 1.03 cells/μl; without cGVHD, 0.44 cells/μl, p=0.042). However, we revealed lower absolute counts of Th EM phenotype (cGVHD, 6 cells/μl; cGVHD-free, 16 cells/μl, p=0.023), and of Th1 EM phenotype (in cases of cGVHD, 1 cell/μl; without cGVHD, 6 cells/μl, p=0.004).
The role of both Th1 and Th22 cells in pathogenesis of cGVHD has been highlighted. IFNy is the main product of Th1 population. IFNy induces the synthesis of CXCL9, CXCL10 and CXCL11 chemokines which are recognized as plasma markers of cGVHD, i.e., their levels are increased at the time of diagnosis and remain high throughout active phase of the disorder. The CXCL9 level also correlates with cGVHD severity and shows a prognostic potential. Interleukin-22 (IL-22) is the main product of Th22 activity. The IL-22 contents correlate with severity of skin lesions in cGVHD. Some “shift” of the phenotype to the central memory pattern may be associated with both damage to the thymus and the applied immunosuppressive therapy. This question seems to us extremely interesting and requires further study in larger samples.
T-helpers, allo-HSCT, chronic GVHD.