Abnormal telomere shortening of peripheral blood mononuclear cells and granulocytes in patients with chronic idiopathic neutropenia

Abstract

BackgroundChronic idiopathic neutropenia is characterized by immune-mediated suppression of neutrophil production. Because patients with immune-mediated bone marrow failure syndromes display age-inappropriate telomere shortening in leukocytes, we investigated telomere lengths in peripheral blood mononuclear cells and granulocytes of patients with chronic idiopathic neutropenia. Design and MethodsWe studied 37 patients with chronic idiopathic neutropenia and 68 age-and sex-matched healthy controls. Relative telomere length and telomerase reverse transcriptase expression were assessed by a quantitative real time polymerase chain reaction. Telomerase activity was determined by a polymerase chain reaction-based immunoassay. ResultsThe mean relative telomere values of peripheral blood mononuclear cells and granulocytes were significantly lower in patients compared to controls, and significantly lower than expected on the basis of the age-adjusted healthy control distribution. The difference in the relative telomere lengths between patients and controls in both peripheral blood mononuclear cells and granulocytes was prominent in those under the age of 50 years. Contrary to the peripheral blood mononuclear cells, in which an inverse correlation was observed between relative telomere values and age, no significant correlation was noted between granulocyte telomere values and patient age. A significant correlation was observed between individual relative telomere values and absolute neutrophil counts. There was no difference in expression of telomerase reverse transcriptase in peripheral blood mononuclear cells between patients and controls but telomerase activity was identified at a significantly higher frequency in controls than in patients. No correlation was found between telomerase activity or telomerase reverse transcriptase expression and relative telomere lengths of peripheral blood mononuclear cells. ConclusionsPatients with chronic idiopathic neutropenia display age-inappropriate telomere shortening of peripheral blood cells and low telomerase activity in peripheral blood mononuclear cells. A compensatory increased proliferation of bone marrow hematopoietic progenitor cells in association with lymphocyte replicative exhaustion probably account for these abnormalities.

Impaired Proliferative Potential of Bone Marrow Mesenchymal Stromal Cells in Patients with Myelodysplastic Syndromes Is Associated with Abnormal WNT Signaling Pathway

“…DNA was extracted from P2, P6, and P10 MSCs using the QIAamp DNA mini kit (Qiagen), and the relative telomere length was evaluated using a previously described semiquantitative real-time PCR method with b-globin as control single-copy gene [25]. SYBR GreenER qPCR Supermix was used for the PCRs.…”

n-3 Fatty Acid Supplementation and Leukocyte Telomere Length in Patients with Chronic Kidney Disease

“…Values are means (SEM) or geometric mean (95% confidence interval (CI)). In order to account for any potential confounding effects of the treatments on leukocyte cell counts that may have influenced DNA telomere length [ 10 , 11 , 12 ], analyses were performed on neutrophil DNA telomere length corrected for neutrophil cell count or PBMC DNA telomere length corrected for PBMC cell count. Regression models were used to explore the relationship between plasma F 2 -isoprostanes and telomere length.…”

“…Smoking and obesity associate with telomere shortening while dietary restriction, increasing dietary fibre or anti-oxidants, or reducing fat or protein intake protect against telomere shortening [ 9 ]. Other factors that may affect telomere length include leukocyte cell counts that positively associate with telomere length [ 10 , 11 , 12 ]. This may be particularly relevant in patients with CKD whose neutrophil cell counts have been shown to be elevated, likely as a result of increased apoptosis [ 13 ].…”

Is chronic neutropenia always a benign disease? Evidences from a 5-year prospective study

“…In idiopathic neutropenia an inhibitory effect of activated T lymphocytes and monocytes on BM granulopoiesis, and an excessive activity of proinflammatory, and proapoptotic cytokines have been reported; on the other hand the presence of anti-neutrophil antibodies, which are involved in immune-mediated destruction of neutrophils, is considered as the hallmark of autoimmune neutropenia [4][5][6]. Moreover, an altered T-cell receptor Vβ repertoire, telomere shortening, and an increased expression/activation of toll-like receptor 4 have been recently reported in patients with chronic idiopathic neutropenia [7][8][9].…”