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Long-lasting production of new T and B cells and T-cell repertoire diversity in patients with primary immunodeficiency who had undergone stem cell transplantation: a single-centre experience.

Valotti M, Sottini A, Lanfranchi A, Bolda F, Serana F, Bertoli D, Giustini V, Tessitore MV, Caimi L, Imberti L - J Immunol Res (2014)

Bottom Line: The mean time of the follow-up was 8 years.Although thymic output decreased in older transplanted patients, the degree of T-cell repertoire diversity, after an initial increase, remained stable during the observation period.However, the presence of graft-versus-host disease and ablative conditioning seemed to play a role in the time-related shaping of T-cell repertoire.

View Article: PubMed Central - PubMed

Affiliation: CREA, Diagnostics Department, Spedali Civili of Brescia, 25123 Brescia, Italy.

ABSTRACT
Levels of Kappa-deleting recombination excision circles (KRECs), T-cell receptor excision circles (TRECs), and T-cell repertoire diversity were evaluated in 1038 samples of 124 children with primary immunodeficiency, of whom 102 (54 with severe combined immunodeficiency and 48 with other types of immunodeficiency) underwent hematopoietic stem cell transplantation. Twenty-two not transplanted patients with primary immunodeficiency were used as controls. Only data of patients from whom at least five samples were sent to the clinical laboratory for routine monitoring of lymphocyte reconstitutions were included in the analysis. The mean time of the follow-up was 8 years. The long-lasting posttransplantation kinetics of KREC and TREC production occurred similarly in patients with severe combined immunodeficiency and with other types of immunodeficiency and, in both groups, the T-cell reconstitution was more efficient than in nontransplanted children. Although thymic output decreased in older transplanted patients, the degree of T-cell repertoire diversity, after an initial increase, remained stable during the observation period. However, the presence of graft-versus-host disease and ablative conditioning seemed to play a role in the time-related shaping of T-cell repertoire. Overall, our data suggest that long-term B- and T-cell reconstitution was equally achieved in children with severe combined immunodeficiency and with other types of primary immunodeficiency.

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((a) and (b)) Average frequency of children with SCID and PID receiving HSCT (HSCT-SCID and HSCT-PID, resp.) or that were not subjects to HSCT (no-HSCT) that show unrestricted T-cell repertoires. The indicated time-classes for HSCT children were calculated starting from the date of HSCT, whereas in no-HSCT children each time-class represents the age at the time of sampling. Time-classes were indicated as follows: 1: <1 year, 2: <2 years, 3: <3 years, 4: <4 years, 5: <5 years, <10: <10 years, and >10: >10 years. Bars represent the means and error bars represent the standard deviations.
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fig2: ((a) and (b)) Average frequency of children with SCID and PID receiving HSCT (HSCT-SCID and HSCT-PID, resp.) or that were not subjects to HSCT (no-HSCT) that show unrestricted T-cell repertoires. The indicated time-classes for HSCT children were calculated starting from the date of HSCT, whereas in no-HSCT children each time-class represents the age at the time of sampling. Time-classes were indicated as follows: 1: <1 year, 2: <2 years, 3: <3 years, 4: <4 years, 5: <5 years, <10: <10 years, and >10: >10 years. Bars represent the means and error bars represent the standard deviations.

Mentions: The mean adjusted frequency of patients having unrestricted T-cell repertoires was only 10% in HSCT-SCID patients at 1 year after transplantation, increased to 40% in the following year, and remained between 40% and 55% in the remaining observation time. Therefore, HSCT-SCID children, in spite of the decreasing mean frequency of normal TREC levels observed at the last two time points of the follow-up, maintained the acquired T-cell heterogeneity. In HSCT-PID patients, the modulation of T-cell repertoire was very similar to that of the previous group (Figure 2(a)), and this was confirmed by a logistic regression analysis showing that the pattern of change over time of the probability of having an unrestricted repertoire did not differ between the two groups (Table 2 and Supplementary Figure 2). In no-HSCT patients the frequency of patients with an unrestricted repertoire was below 40% in all time-classes, except in 5-year-old patients, in whom it reached 57% (Figure 2(b)). This significantly lower frequency of patients with an unrestricted repertoire among the no-HSCT patients was also demonstrated by logistic regression (Table 3, Supplementary Figure 3).


Long-lasting production of new T and B cells and T-cell repertoire diversity in patients with primary immunodeficiency who had undergone stem cell transplantation: a single-centre experience.

Valotti M, Sottini A, Lanfranchi A, Bolda F, Serana F, Bertoli D, Giustini V, Tessitore MV, Caimi L, Imberti L - J Immunol Res (2014)

((a) and (b)) Average frequency of children with SCID and PID receiving HSCT (HSCT-SCID and HSCT-PID, resp.) or that were not subjects to HSCT (no-HSCT) that show unrestricted T-cell repertoires. The indicated time-classes for HSCT children were calculated starting from the date of HSCT, whereas in no-HSCT children each time-class represents the age at the time of sampling. Time-classes were indicated as follows: 1: <1 year, 2: <2 years, 3: <3 years, 4: <4 years, 5: <5 years, <10: <10 years, and >10: >10 years. Bars represent the means and error bars represent the standard deviations.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4270024&req=5

fig2: ((a) and (b)) Average frequency of children with SCID and PID receiving HSCT (HSCT-SCID and HSCT-PID, resp.) or that were not subjects to HSCT (no-HSCT) that show unrestricted T-cell repertoires. The indicated time-classes for HSCT children were calculated starting from the date of HSCT, whereas in no-HSCT children each time-class represents the age at the time of sampling. Time-classes were indicated as follows: 1: <1 year, 2: <2 years, 3: <3 years, 4: <4 years, 5: <5 years, <10: <10 years, and >10: >10 years. Bars represent the means and error bars represent the standard deviations.
Mentions: The mean adjusted frequency of patients having unrestricted T-cell repertoires was only 10% in HSCT-SCID patients at 1 year after transplantation, increased to 40% in the following year, and remained between 40% and 55% in the remaining observation time. Therefore, HSCT-SCID children, in spite of the decreasing mean frequency of normal TREC levels observed at the last two time points of the follow-up, maintained the acquired T-cell heterogeneity. In HSCT-PID patients, the modulation of T-cell repertoire was very similar to that of the previous group (Figure 2(a)), and this was confirmed by a logistic regression analysis showing that the pattern of change over time of the probability of having an unrestricted repertoire did not differ between the two groups (Table 2 and Supplementary Figure 2). In no-HSCT patients the frequency of patients with an unrestricted repertoire was below 40% in all time-classes, except in 5-year-old patients, in whom it reached 57% (Figure 2(b)). This significantly lower frequency of patients with an unrestricted repertoire among the no-HSCT patients was also demonstrated by logistic regression (Table 3, Supplementary Figure 3).

Bottom Line: The mean time of the follow-up was 8 years.Although thymic output decreased in older transplanted patients, the degree of T-cell repertoire diversity, after an initial increase, remained stable during the observation period.However, the presence of graft-versus-host disease and ablative conditioning seemed to play a role in the time-related shaping of T-cell repertoire.

View Article: PubMed Central - PubMed

Affiliation: CREA, Diagnostics Department, Spedali Civili of Brescia, 25123 Brescia, Italy.

ABSTRACT
Levels of Kappa-deleting recombination excision circles (KRECs), T-cell receptor excision circles (TRECs), and T-cell repertoire diversity were evaluated in 1038 samples of 124 children with primary immunodeficiency, of whom 102 (54 with severe combined immunodeficiency and 48 with other types of immunodeficiency) underwent hematopoietic stem cell transplantation. Twenty-two not transplanted patients with primary immunodeficiency were used as controls. Only data of patients from whom at least five samples were sent to the clinical laboratory for routine monitoring of lymphocyte reconstitutions were included in the analysis. The mean time of the follow-up was 8 years. The long-lasting posttransplantation kinetics of KREC and TREC production occurred similarly in patients with severe combined immunodeficiency and with other types of immunodeficiency and, in both groups, the T-cell reconstitution was more efficient than in nontransplanted children. Although thymic output decreased in older transplanted patients, the degree of T-cell repertoire diversity, after an initial increase, remained stable during the observation period. However, the presence of graft-versus-host disease and ablative conditioning seemed to play a role in the time-related shaping of T-cell repertoire. Overall, our data suggest that long-term B- and T-cell reconstitution was equally achieved in children with severe combined immunodeficiency and with other types of primary immunodeficiency.

Show MeSH
Related in: MedlinePlus