The response rate in severe aplastic anemia patients with increased IFN-γ levels in the blood plasma was higher than that in severe aplastic anemia patients with decreased IFN-γ levels in the blood plasma (73.7% vs. 25.0%, p<0.05).
However, if such a donor is not available, any single-allele or multiple-allele (HLA-C, -DRB1, -DQB1) mismatched donor is acceptable as an unrelated donor for patients with severe aplastic anemia.
However, if such a donor is not available, any single-allele or multiple-allele (HLA-C, -DRB1, -DQB1) mismatched donor is acceptable as an unrelated donor for patients with severe aplastic anemia.
Employing unbiased RNA amplification, patient-specific gene expression profiling was carried out for CD34(+) cells from patients newly diagnosed with very severe aplastic anemia (n=13), refractory anemia (n=8) and healthy controls (n=10).
CD34+ gene expression profiling of individual children with very severe aplastic anemia indicates a pathogenic role of integrin receptors and the proapoptotic death ligand TRAIL.
Next-generation-sequencing-spectratyping reveals public T-cell receptor repertoires in pediatric very severe aplastic anemia and identifies a β chain CDR3 sequence associated with hepatitis-induced pathogenesis.
In peripheral T cells from patients with untreated AA, NOTCH1(IC) was significantly elevated and bound to the TBX21 promoter, showing NOTCH1 directly regulates the gene encoding T-BET.
In peripheral T cells from patients with untreated AA, NOTCH1(IC) was significantly elevated and bound to the TBX21 promoter, showing NOTCH1 directly regulates the gene encoding T-BET.
The gene frequencies of A(∗)02:01, A(∗)02:06, B(∗)13:01, DRB1(∗)07:01, DRB1(∗)09:01, DRB1(∗)15:01 and DQB1(∗)06:02 in SAA patients were significantly higher than in controls (all P<0.05), while the allelic frequencies of A(∗)02:07, A(∗)11:01 and B(∗)40:01 were notably lower in SAA patients than those in the controls (P = 0.001, 0.002, 0.005, respectively).
The gene frequencies of A(∗)02:01, A(∗)02:06, B(∗)13:01, DRB1(∗)07:01, DRB1(∗)09:01, DRB1(∗)15:01 and DQB1(∗)06:02 in SAA patients were significantly higher than in controls (all P<0.05), while the allelic frequencies of A(∗)02:07, A(∗)11:01 and B(∗)40:01 were notably lower in SAA patients than those in the controls (P = 0.001, 0.002, 0.005, respectively).
In CD34(+) cells, Fas expression was significantly higher in the newly diagnosed SAA group (46.59 ± 27.60%) than the remission (6.12 ± 3.35%; P < 0.01) and control (8.89 ± 7.28%; P < 0.01) groups.
Therefore, we concluded that the decrease of total NK cells, and CD56(bright), CD56(dim) NK cell subsets and the higher expressions of NKp46 and perforin on NK cells may cause the over-function of T lymphocytes and thus lead to hematopoiesis failure in SAA.
The expression of perforin, granzyme B, TNF-β and FasL in CD8+HLA-DR+ T cells was analyzed by flow cytometry and PCR, which revealed increased expression in the untreated SAA group compared with that in the control group.
We compared and analyzed HLA-A, B, C, DRB1 and DQB1 alleles in 96 Chinese severe AA (SAA) patients to those in 600 healthy people chosen randomly from the China Marrow Donor Program to investigate the association of HLA class I and II allele polymorphisms with disposition of SAA and its severity degree in Chinese population.
In CD14(+), CD33(+), and GlycoA(+) cells, Fas levels were significantly lower in the newly diagnosed SAA group (29.29 ± 9.23, 46.88 ± 14.30, and 15.15 ± 9.26%, respectively) than in the remission (47.23 ± 31.56, 67.22 ± 34.68, and 43.56 ± 26.85%, respectively; P < 0.05) and normal control (51.25 ± 38.36, 72.06 ± 39.88, 50.38 ± 39.88%, respectively; P < 0.05) groups.
Apoptosis of CD8+HLA-DR+ cells was detected by flow cytometry following staining with Annexin V. The proportion of CD8+HLA-DR+ T cells was analyzed by flow cytometry in peripheral blood and was identified to be significantly higher in untreated SAA than in remission patients and in the controls.
Patients with SAA had an increased levels of LAT and both total phosphorylated LAT and of the related molecule (ZAP-70) in circulating T cells compared with normal controls.
Therefore, we concluded that the decrease of total NK cells, and CD56(bright), CD56(dim) NK cell subsets and the higher expressions of NKp46 and perforin on NK cells may cause the over-function of T lymphocytes and thus lead to hematopoiesis failure in SAA.
In CD14(+), CD33(+), and GlycoA(+) cells, Fas levels were significantly lower in the newly diagnosed SAA group (29.29 ± 9.23, 46.88 ± 14.30, and 15.15 ± 9.26%, respectively) than in the remission (47.23 ± 31.56, 67.22 ± 34.68, and 43.56 ± 26.85%, respectively; P < 0.05) and normal control (51.25 ± 38.36, 72.06 ± 39.88, 50.38 ± 39.88%, respectively; P < 0.05) groups.
Improving diagnostic precision, care and syndrome definitions using comprehensive next-generation sequencing for the inherited bone marrow failure syndromes.