Plasma IL-18, IFN-γ and IL-4 levels were measured in patients with newly diagnosed AA (n = 29), AA in remission (n = 22) and healthy subjects (n = 30) via enzyme-linked immunosorbent assay (ELISA).
Eight SNP loci in five cytokine genes, including tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), transforming growth factor-beta (TGF-β), interleukin-6 (IL-6), and IL-10, and aplastic anemia (AA) were assessed.
Blocking the transcription of the IFN-gamma gene with kinase inhibitors might lead to the development of novel therapeutic agents for patients with aplastic anemia and other autoimmune diseases.
The results showed that the frequency of IFN-γ +874 TT genotype in patients with aplastic anemia was significantly higher than the corresponding frequency in the healthy adults (42.6% vs. 17.6%, χ(2)=13.78, p=0.01).
Our findings suggest that alterations in KIR/KIR-L matching, such as increased 3DL2 and decreased 2DS1 mismatch, and in the polymorphisms of TGFβ1, IFN-γ, TNF- α and IL-10 may account for the propensity to immunemediated killing of hematopoietic stem cells and/or ineffective hematopoiesis characteristic of AA and MDS.
The concentration of interferon-γ and interleukin-17 in the AA group were higher (<i>p</i> = 0.004; <i>p</i> = 0.003), whereas the concentration of <i>TGF-β</i> decreased (<i>p</i> = 0.044).
Homozygosis for (12) CA repeats in the first intron of the human IFN-gamma gene is significantly associated with the risk of aplastic anaemia in Caucasian population.
Interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) have been implicated historically in the immune pathophysiology of aplastic anemia (AA) and other bone marrow (BM) failure syndromes.
T cells from aplastic anemia (AA) patients secrete IFN-gamma in vitro, activated cytotoxic lymphocytes infiltrate aplastic bone marrow (BM), and IFN-gamma mRNA, not detected in normal BM, is present in BM from most AA patients.
The data suggest that AA occurs when IFN-γ inhibits the generation of myeloid progenitors and prevents lineage differentiation, as opposed to infiltration of activated T cells.
Comparison between the IFN-gamma transcriptome in normal CD34 cells and changes previously detected in CD34 cells from AA and PNH patients reveals the presence of many similarities that may reflect molecular signature of in vivo IFN-gamma exposure.
Interleukin (IL)-18 is a potent pro-inflammatory cytokine capable of inducing interferon-gamma production that is associated with the development of T1DM.
IL-18 and IFN-γ have also been implicated in the onset of different types of immune-mediate inflammatory conditions such as Type 1 Diabetes (T1D), Celiac disease (CD), rheumatoid arthritis (RA), obesity and systemic lupus erythematosus (SLE).
The aim of this study was to investigate the frequency of a CA dinucleotide repeat polymorphism in the interferon-gamma (IFN-gamma) gene (IFNG) and a C(-590)T polymorphism of the interleukin-4 (IL-4) gene in 236 Caucasoid patients with type 1 diabetes.
These findings suggest that the increased peripheral B:9-23rPep-specific IFN-γ immunoreactivity reflects decreased functional β-cell mass and greater disease activity of type 1 diabetes.
On the other hand, higher ketoacidosis at onset, younger age at onset, and higher levels of tumor necrosis factor-alpha and interferon-gamma were observed in T1D patients carriers of G allele in comparison with the carriers of AA genotype.
IGRP(265-273)-specific CD8 T-cells that were cloned from the peripheral blood of a recent onset T1D individual were shown to secrete IFNγ and Granzyme B after antigen-specific activation and lyse HLA-A2-expressing murine islets in-vitro.