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Flow cytometric analysis of the CD4+ TCR Vβ repertoire in the peripheral blood of children with type 1 diabetes mellitus, systemic lupus erythematosus and age-matched healthy controls.

Tzifi F, Kanariou M, Tzanoudaki M, Mihas C, Paschali E, Chrousos G, Kanaka-Gantenbein C - BMC Immunol. (2013)

Bottom Line: Data regarding the quantitative expression of TCR Vβ subpopulations in children with autoimmune diseases provided interesting and sometimes conflicting results.Statistical analysis revealed that the CD4 + Vβ4 chain was significantly increased in patients with T1DM (p < 0.001), whereas CD4 + Vβ16 one was significantly increased in SLE patients (p < 0.001) compared to controls.CD4 + Vβ4 and CD4 + Vβ16 chains could be possibly involved in the cascade of events precipitating the pathogenesis of T1DM and SLE in children, respectively.

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ABSTRACT

Background: Data regarding the quantitative expression of TCR Vβ subpopulations in children with autoimmune diseases provided interesting and sometimes conflicting results. The aim of the present study was to assess by comparative flow cytometric analysis the peripheral blood CD4+ TCR Vβ repertoire of children with an organ-specific autoimmune disorder, such as type 1 diabetes mellitus (T1DM), in comparison to children with a systemic autoimmune disease, such as Systemic Lupus Erythematosus (SLE) in comparison to healthy age-matched controls of the same ethnic origin. The CD4+ TCR Vβ repertoire was analysed by flow cytometry in three groups of participants: a) fifteen newly diagnosed children with T1DM (mean age: 9.2 ± 4.78 years old), b) nine newly diagnosed children with SLE, positive for ANA and anti-dsDNA, prior to treatment (mean age: 12.8 ±1.76 years old) and c) 31 healthy age-matched controls (mean age: 6.58 ± 3.65 years old), all of Hellenic origin.

Results: CD4 + TCR Vβ abnormalities (± 3SD of controls) were observed mainly in SLE patients. Statistical analysis revealed that the CD4 + Vβ4 chain was significantly increased in patients with T1DM (p < 0.001), whereas CD4 + Vβ16 one was significantly increased in SLE patients (p < 0.001) compared to controls.

Conclusions: CD4 + Vβ4 and CD4 + Vβ16 chains could be possibly involved in the cascade of events precipitating the pathogenesis of T1DM and SLE in children, respectively.

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Comparison of CD4 + Vβ16 chain values among the 3 groups of children studied. Values (%) of the CD4 + Vβ16 chain are higher in the majority of SLE children in comparison to controls.
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Figure 7: Comparison of CD4 + Vβ16 chain values among the 3 groups of children studied. Values (%) of the CD4 + Vβ16 chain are higher in the majority of SLE children in comparison to controls.

Mentions: In the SLE group, skewing in CD4 + Vβ subpopulations was detected in the majority of patients when compared to healthy individuals. In contrast to healthy children and T1DM patients, which presented with a similar CD4 + TCR Vβ repertoire pattern, 7 of the 9 SLE children tested displayed concurrently marked increased (mean value ± 3SD) and decreased usage (with even values of 0.0%) of several CD4 + Vβ subpopulations. This was noteworthy in one SLE patient who displayed increased usage of the CD4+ Vβ12 (9.44%), Vβ16 (5.6%) and Vβ20 (9.17%) and a decreased one of Vβ2 (2.83%) and Vβ5.1 (0.12%) chains and in another one patient with high values of CD4+ Vβ3 (9%), Vβ12 (14.2%) and Vβ16 (7.3%) chains and very low values of CD4+ Vβ2 (0.2%), Vβ5.2 (0.2%), Vβ7.1 (0.1%) and Vβ22 (0.3%) (Table 6, Figure 5). Markedly low values were found in the following CD4 + Vβ chains: Vβ2 (in 2 patients), Vβ22 (in 2 patients), Vβ5.1, Vβ5.2, Vβ7.1, Vβ8, Vβ13.6, and Vβ18. The CD4 + Vβ4 subpopulation had values of 0.0% in three SLE patients. However, this finding, as previously mentioned, was noticed in healthy children as well. Increased usage of Vβ16 was found in 5, of Vβ4 in 2, of Vβ20 in 2 and of Vβ12 in 2 patients. It should be mentioned, though, that there were two SLE patients with a normal repertoire at initial diagnosis. When statistical analysis was performed in order to compare the CD4 + Vβ expression between SLE and healthy children, significant differences in TCR Vβ quantitative expression were noticed only for the Vβ16 chain (p <0.001) (Table 3, Figure 6). This was expected, since five SLE patients presented with higher values of the CD4 + Vβ16 chain than those of the control group (mean value + 3SD) (Figure 7). Only one healthy individual presented an increased usage of CD4 + Vβ16, but he displayed no other discrepancies of the rest CD4 + Vβ subfamilies.


Flow cytometric analysis of the CD4+ TCR Vβ repertoire in the peripheral blood of children with type 1 diabetes mellitus, systemic lupus erythematosus and age-matched healthy controls.

Tzifi F, Kanariou M, Tzanoudaki M, Mihas C, Paschali E, Chrousos G, Kanaka-Gantenbein C - BMC Immunol. (2013)

Comparison of CD4 + Vβ16 chain values among the 3 groups of children studied. Values (%) of the CD4 + Vβ16 chain are higher in the majority of SLE children in comparison to controls.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750582&req=5

Figure 7: Comparison of CD4 + Vβ16 chain values among the 3 groups of children studied. Values (%) of the CD4 + Vβ16 chain are higher in the majority of SLE children in comparison to controls.
Mentions: In the SLE group, skewing in CD4 + Vβ subpopulations was detected in the majority of patients when compared to healthy individuals. In contrast to healthy children and T1DM patients, which presented with a similar CD4 + TCR Vβ repertoire pattern, 7 of the 9 SLE children tested displayed concurrently marked increased (mean value ± 3SD) and decreased usage (with even values of 0.0%) of several CD4 + Vβ subpopulations. This was noteworthy in one SLE patient who displayed increased usage of the CD4+ Vβ12 (9.44%), Vβ16 (5.6%) and Vβ20 (9.17%) and a decreased one of Vβ2 (2.83%) and Vβ5.1 (0.12%) chains and in another one patient with high values of CD4+ Vβ3 (9%), Vβ12 (14.2%) and Vβ16 (7.3%) chains and very low values of CD4+ Vβ2 (0.2%), Vβ5.2 (0.2%), Vβ7.1 (0.1%) and Vβ22 (0.3%) (Table 6, Figure 5). Markedly low values were found in the following CD4 + Vβ chains: Vβ2 (in 2 patients), Vβ22 (in 2 patients), Vβ5.1, Vβ5.2, Vβ7.1, Vβ8, Vβ13.6, and Vβ18. The CD4 + Vβ4 subpopulation had values of 0.0% in three SLE patients. However, this finding, as previously mentioned, was noticed in healthy children as well. Increased usage of Vβ16 was found in 5, of Vβ4 in 2, of Vβ20 in 2 and of Vβ12 in 2 patients. It should be mentioned, though, that there were two SLE patients with a normal repertoire at initial diagnosis. When statistical analysis was performed in order to compare the CD4 + Vβ expression between SLE and healthy children, significant differences in TCR Vβ quantitative expression were noticed only for the Vβ16 chain (p <0.001) (Table 3, Figure 6). This was expected, since five SLE patients presented with higher values of the CD4 + Vβ16 chain than those of the control group (mean value + 3SD) (Figure 7). Only one healthy individual presented an increased usage of CD4 + Vβ16, but he displayed no other discrepancies of the rest CD4 + Vβ subfamilies.

Bottom Line: Data regarding the quantitative expression of TCR Vβ subpopulations in children with autoimmune diseases provided interesting and sometimes conflicting results.Statistical analysis revealed that the CD4 + Vβ4 chain was significantly increased in patients with T1DM (p < 0.001), whereas CD4 + Vβ16 one was significantly increased in SLE patients (p < 0.001) compared to controls.CD4 + Vβ4 and CD4 + Vβ16 chains could be possibly involved in the cascade of events precipitating the pathogenesis of T1DM and SLE in children, respectively.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Background: Data regarding the quantitative expression of TCR Vβ subpopulations in children with autoimmune diseases provided interesting and sometimes conflicting results. The aim of the present study was to assess by comparative flow cytometric analysis the peripheral blood CD4+ TCR Vβ repertoire of children with an organ-specific autoimmune disorder, such as type 1 diabetes mellitus (T1DM), in comparison to children with a systemic autoimmune disease, such as Systemic Lupus Erythematosus (SLE) in comparison to healthy age-matched controls of the same ethnic origin. The CD4+ TCR Vβ repertoire was analysed by flow cytometry in three groups of participants: a) fifteen newly diagnosed children with T1DM (mean age: 9.2 ± 4.78 years old), b) nine newly diagnosed children with SLE, positive for ANA and anti-dsDNA, prior to treatment (mean age: 12.8 ±1.76 years old) and c) 31 healthy age-matched controls (mean age: 6.58 ± 3.65 years old), all of Hellenic origin.

Results: CD4 + TCR Vβ abnormalities (± 3SD of controls) were observed mainly in SLE patients. Statistical analysis revealed that the CD4 + Vβ4 chain was significantly increased in patients with T1DM (p < 0.001), whereas CD4 + Vβ16 one was significantly increased in SLE patients (p < 0.001) compared to controls.

Conclusions: CD4 + Vβ4 and CD4 + Vβ16 chains could be possibly involved in the cascade of events precipitating the pathogenesis of T1DM and SLE in children, respectively.

Show MeSH
Related in: MedlinePlus