Objectives
Graft-versus-host disease (GvHD) is a complex clinical syndrome with organ dysfunction as a consequence of a severe immunological reaction mediated by mainly T cells after hematopoietic stem cell transplantation. Our aim is to evaluate the association of HLA-DRB1 alleles, IFN-γ and TGF-β gene variations, with childhood ALL (c-ALL) patients and with GvHD after transplantation.
Methods
This study included 30 high-risk c-ALL patients and 100 controls. HLA-DRB1 alleles were studied by the NGS method, and TGF-β and IFN-γ variations were studied by the PCR-RFLP method.
Results
The rates of HLA-DRB1*15 alleles and IFN-gamma CC genotype were significantly higher in c-ALL patients (p=0.004, p=0.036 respectively). Association of the HLA-DRB1*15 alleles with the TGF-β TC genotype was found with a higher rate in the patient group (p=0.031). Association of the DRB1*04 allele with the IFN-γ CC genotype was found with a higher rate in the patient group (p=0.028). Acute GvHD developed in eight of 19 patients who underwent transplantation. IFN-γ CT was found to have a protective role in occurrence of aGvHD (p=0.044). Association of the DRB1*15 allele with IFN-γ TT was found with a higher rate in a GvHD (p=0.050).
Conclusions
It is thought that polymorphism of HLA-DR15 and IFN-γ CC may contribute to the development of c-ALL, while IFN-γ CT might be protective for aGvHD.
Determination of the immunomodulatory properties of mesenchymal stem cells (MSCs) is necessary before clinical applications. In this study, it was aimed to determine the effect of MSCs on cytokines secreted by the immune system cells.Intracellular cytokine levels (Interleukin-4 (IL-4), Interferon-γ (IFN-γ), and Interleukin-17 (IL-17)) detected by ow cytometry before and after co-culture between peripheral blood mononuclear cells (PBMCs) and MCSs. At the same time, supernatant cytokine levels were measured using the ELISA. In our study, MSCs were isolated from cord blood (CB) and Wharton's Jelly (WJ), and their surface markers (CD44 (100%), CD73 (99.6%), CD90 (100%), CD105 ( 88%))shown by ow cytometry method. Both CB-MSCs and WJ-MSCs were used in co-culture MSC/PBMC ratios of 1/5 and 1/10, incubation times of 24 hours and 72 hours.In the present study, when we compared co-cultures of CB-MSC or WJ-MSC with PBMCs, intracellular levels of cytokines IFN-γ, IL-17 (pro-in amatory) and IL-4 (anti-in amatory) were increased and supernatant levels were decreased signi cantly (p < 0.05). The level of TGF-β (anti-in amatory) was signi cantly decreased for both CB-MSC and WJ-MSC in supernatant (p < 0.05).It was investigated the pro-in ammatory and anti-in ammatory effects of CB-MSCs and WJ-MSCs on PBMCs with the obtained results. According to the results, MSCs demonstrated different immunologic effects after the incubation time and ratios For further studies, it should be known between interaction of MSCs and immune system.
Objectives
The data of the monocyte subgroups and expressed toll like receptors (TLR) in the innate immune system response, which develop against chronic inflammation in patients with predialysis chronic kidney disease (CKD) and in patients who undergo dialysis treatment, are limited. We aimed to investigate the effect of the dialysis procedure on the current chronic inflammatory condition and which role of monocyte subgroups ratios, the expressions of TLR2/4 and serum Tumor necrosis factor alpha (TNF-α) levels involved in the innate immune response process.
Methods
We investigated monocyte subgroups, TLR2/TLR4 expressions and serum TNF-α levels in 30 predialysis CKD patients, 90 CKD patients undergoing dialysis and 30 healthy control subjects. Monocyte subgroup percentages and TLR2/TLR4 expressions were determined using the flow cytometry, serum TNF-α levels were investigated using the enzyme-linked immunosorbent assay (ELISA).
Results
In the dialysis patients, the percentages of classical (p=0.0001) and non-classical (p=0.078) monocytes were found to be higher when compared with the predialysis CKD patients. The percentages of TLR4 expression on non-classical monocytes was higher in dialysis and predialysis patients compared with the healthy controls (p<0.0001, p=0.796). Serum TNF-α level was significantly higher in dialysis and predialysis patients compared with the healthy controls (p=0.013, p=0.022) and a positive correlation between the classical monocyte subgroup and TNF-α was observed (r=0.285, p=0.006).
Conclusions
Increased percentages of non-classical monocytes, TLR4 expressions and serum TNF-α levels observed in the predialysis CKD patients and dialysis patients might be related to inflammation.
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