Profiles of interferon-gamma and interleukin-2 in patients after allogeneic hematopoietic stem cell transplantation

Malwina Rybicka-Ramos; Mirosław Markiewicz; Aleksandra Suszka-Świtek; Ryszard Wiaderkiewicz; Sylwia Mizia; Monika Dzierżak-Mietła; Krzysztof Białas

doi:10.4331/wjbc.v13.i4.72

Profiles of interferon-gamma and interleukin-2 in patients after allogeneic hematopoietic stem cell transplantation

World J Biol Chem. 2022 Sep 27;13(4):72-82. doi: 10.4331/wjbc.v13.i4.72.

Authors

Malwina Rybicka-Ramos¹, Mirosław Markiewicz², Aleksandra Suszka-Świtek³, Ryszard Wiaderkiewicz³, Sylwia Mizia⁴, Monika Dzierżak-Mietła⁵, Krzysztof Białas⁶

Affiliations

¹ Department of Hematology, Specialist Hospital No. 1 in Bytom, Bytom 41-902, Poland. malwina.rybicka@gmail.com.
² Department of Hematology, University of Rzeszow, College of Medical Sciences, Institute of Medical Sciences, Rzeszów 35-315, Poland.
³ Department of Histology and Embryology, School of Medicine in Katowice, Medical University of Silesia, Katowice 40-752, Poland.
⁴ Department of Population Health, Division of Epidemiology and Health Education, Wroclaw Medical University, Wrocław 51-618, Poland.
⁵ Department of Bone Marrow Transplantation and Hematooncology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice 44-102, Poland.
⁶ Department of Hematology and Bone Marrow Transplantation, SPSK-M Hospital, Katowice 40-027, Poland.

Abstract

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be related to the occurrence of complications, including graft-versus-host disease (GvHD) and infections. The pathogenesis of acute GvHD is connected with T lymphocytes, which identify alloantigens on host's antigen-presenting cells, activate production of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2), and act on the immune effector cells and damage tissues and organs.

Aim: The aim of the study was to investigate and distinguish serum concentration profiles of IFN-gamma and IL-2 within a 30-d period after allo-HSCT.

Methods: We enrolled 62 patients, i.e., 30 (48%) male and 32 (52%) female subjects [median age 49.5 (19-68) years], after allo-HSCT from siblings (n = 12) or unrelated donors (n = 50) due to acute myeloid leukemia with myeloablative conditioning (n = 26; 42%) and with non-myeloablative conditioning (n = 36; 58%). All patients were given standard immunosuppressive therapy with cyclosporin-A and methotrexate and pre-transplant antithymocyte globulin in the unrelated setting. Blood samples were collected pre-transplant before and after (on day -1) the conditioning therapy and on days +2,+4, +6, +10, +20, and +30 after allo-HSCT. Serum levels of IL-2 and IFN-gamma were determined using ELISA.

Results: Patients were divided into four groups depending on the presence of acute GvHD and clinical manifestations of infection. Group I included patients with neither acute GvHD nor infections [n = 15 (24%)], group II consisted of patients with infections without acute GvHD [n = 17 (27%)], group III was comprised of patients with acute GvHD without infections [n = 9 (15%)], and group IV included patients with both acute GvHD and infections [n = 21 (34%)]. IFN-gamma concentrations were higher in Group II than in other groups on days +20 (P = 0.014) and +30 (P = 0.008). Post-hoc tests showed lower concentrations of IFN-gamma on day +30 in groups I (P = 0.039) and IV (P = 0.017) compared to group II. The levels of IL-2 were mostly undetectable.

Conclusion: Serum levels of IFN-gamma following allo-HSCT progressively escalate. High serum levels of IFN-gamma are related to infectious complications rather than acute GvHD. Serum concentrations of IL-2 in most patients are undetectable.

Keywords: Acute graft-versus-host disease; Acute myeloid leukemia; Allogeneic hematopoietic stem cell transplantation; Cytokine profiles; Interferon-gamma; Interleukin-2.