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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Thymopoiesis in Pre- and Post-Hematopoietic Stem Cell Transplantation

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Author(s):
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da Rocha, Luis Klaus A. [1] ; de Barros, Samar Freschi [1] ; Bandeira, Francine [2] ; Bollini, Alexia [2] ; Testa, Lucia Helena de A. [2] ; Simione, Anderson Joao [2] ; Souza, Marina de O. e [2] ; Zanetti, Lilian P. [2] ; de Oliveira, Leila Cibele S. [2] ; dos Santos, Ana Claudia F. [2] ; de Souza, Mair Pedro [2] ; Colturado, Vergilio Antonio R. [2] ; Kalil, Jorge [1] ; Machado, Clarisse M. [3] ; Guilherme, Luiza [1]
Total Authors: 15
Affiliation:
[1] Univ Sao Paulo, Heart Inst InCor, Clin Hosp, Lab Immunol, Sao Paulo - Brazil
[2] Amaral Carvalho Hosp, Hematopoiet Stem Cell Transplantat Sect, Jau - Brazil
[3] Univ Sao Paulo, Trop Med Inst IMT, Lab Virol, Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: FRONTIERS IN IMMUNOLOGY; v. 9, SEP 7 2018.
Web of Science Citations: 2
Abstract

Hematopoietic stem cell transplantation (HSCT) is an important therapeutic option for some hematological diseases. However, patients who undergo HSCT acquire a state of immunodeficiency that causes significant mortality. Reconstitution of thymic function is needed to support the immune system. One way to measure thymic function is through T-cell receptor excision circle (TREC) quantification. TRECs are generated by T-cell receptor gene rearrangements during T-cell maturation in the thymus and represent a reliable marker for thymic output. In this study, we aimed to assess aging and malignant hematological diseases as two important factors that may influence thymic output before HSCT. We observed that patients before HSCT presented signal joint TREC (sjTREC) numbers lower than 606.55 copies/mu g DNA (low values) compared with healthy individuals, with an odds ratio (OR) of 12.88 {[}95% confidence interval (CI): 5.26-31.53; p < 0.001]. Our results showed that a group of older individuals (>= 50 years old), comprising both healthy individuals and patients, had an OR of 10.07 (95% CI: 2.80-36.20) for low sjTREC values compared with younger individuals (<= 24 years old; p < 0.001). Multiple logistic regression analysis confirmed that both older age (>= 50 years old) and malignant hematological diseases and their treatments were important and independent risk factors related to thymic function impairment (p < 0.001). The median sjTREC value for patients of all ages was significantly lower than the sjTREC median for the subgroup of older healthy individuals (>= 50 years old; p < 0.001). These data suggested that patients before HSCT and healthy individuals exhibited age-dependent thymic impairment, and that prior treatment for hematological diseases may exacerbate aging-related deterioration of natural thymic function. Furthermore, we analyzed these patients 9 months post-HSCT and compared patients who underwent autologous HSCT with those who underwent allogeneic HSCT. Both groups of patients achieved sjTREC copy numbers similar to those of healthy individuals. We did not find a close relationship between impaired thymic function prior to HSCT and worse thymic recovery after HSCT. (AU)

FAPESP's process: 14/02879-2 - Evaluation of lymphoid T immune recovery after hematopoietic stem cell transplant in patients with previous diagnosis of acute leukemia or myelodysplastic syndrome
Grantee:Luiza Guglielmi
Support Opportunities: Regular Research Grants