Telomere length correlates with disease severity and inflammation in sickle cell disease

Abstract

BackgroundTelomeres, the ends of linear chromosomes, shorten during mitotic cell division and erosion may be aggravated by inflammation or proliferative and oxidative stress. As the bone marrow is under hyperproliferative pressure in sickle cell disease and several tissues are submitted to chronic inflammation, this study sought to determine the telomere length of patients with sickle cell disease.MethodsThe mean telomere length was measured in peripheral blood leukocytes by quantitative polymerase chain reaction. The age-adjusted telomere to single copy gene ratio was compared between 91 adult sickle cell disease patients and 188 controls.ResultsSickle cell disease patients had significantly shorter telomeres than the controls (p-value < 0.0001). Moreover, among sickle cell disease genotypes, Hb SS patients had significantly shorter telomeres compared to Hb SC and Hb Sβ patients (p-value < 0.0001). Patients on hydroxyurea also had shorter telomeres in comparison to those off the drug (p-value = 0.02). A positive correlation was observed between telomere length and hemoglobin level (r = 0.3; p-value = 0.004), whereas negative correlations were detected between telomere length and lymphocyte count (r = −0.3; p-value = 0.005) and interleukin-8 serum levels (r = −0.4; p-value = 0.02).ConclusionsThe findings of this study indicate that telomeres are short in sickle cell disease patients and that telomere erosion directly correlates with disease genotype, inflammation markers, and the use of hydroxyurea.

Stressed ends: telomere attrition in chronic diseases

“…The prevalent theory is that inflammation and oxidative stress trigger a faster immune cell turnover, which in turn leads to a shorter LTL 9 . This is in line with the data shown by Colella et al , in this issue of the Brazilian Journal of Hematology and Hemotherapy 10 . In their work, the authors analyzed telomere lengths from peripheral blood leukocytes of sickle cell disease (SCD) patients.…”

“…Combined, the results presented by Colella et al , indicate that in SCD, inflammation and oxidative stress (elevated oxidative stress burden is a well-established occurrence in SCD) also contribute to telomere attrition. 10 While future studies should continue to decipher the role of telomere length and human disease, and establish if telomere attrition plays a direct role in disease progression, the data showed by Colella et al in this issue help cement the importance of telomere biology as a marker of cellular and organismal health.…”

“… 9 This is in line with the data shown by Colella et al , in this issue of the Brazilian Journal of Hematology and Hemotherapy. 10 In their work, the authors analyzed telomere lengths from peripheral blood leukocytes of sickle cell disease (SCD) patients. The authors demonstrated by different methods that telomeres are significantly shorter in SCD patients in comparison to age-matched controls.…”

Safety and efficacy of plerixafor dose escalation for the mobilization of CD34 + hematopoietic progenitor cells in patients with sickle cell disease: interim results

“…Other studies of plerixafor in SCD 4 , 32 have initiated chronic transfusion based on the hypothesis that the inflammatory nature of SCD affects the bone marrow and transfusion assuages bone marrow inflammation and stress erythropoiesis. Although replicative and oxidative stress of HPC in bone marrow may occur, 41 – 44 there is limited evidence that HPC are damaged in SCD. 36 Five of our patients had HbF-associated increases in hemoglobin concentration and hematocrit to more than 10 g/dL and 30%, respectively (similar to values in chronically transfused patients) but HbF levels did not correlate with CD34 cell mobilization.…”

Telomere length and telomere repeat-binding protein in children with sickle cell disease

“…On the contrary, an in vitro study showed that hydroxyurea (HU), an important drug therapy for sickle cell anemia that prolongs survival, affects telomere replication and reduces the telomere DNA synthesis rate through a mechanism that may involve TRF2 direct modification. 23 So far, two studies determined leukocyte TL in adult SCD patients 24,25 and showed conflicting results. Interestingly, no study has been reported in children with SCD.…”