We examined CD4+ T cell TCRBV-CDR3 transcripts from 19 lupus patients and 16 controls to test the hypothesis that CD4+ TCRBV-CDR3 expression in SLE differs from normals. Within the disease group we also performed exploratory analyses to determine the association between risk of oligoclonality and HLA-DRB specificities and the duration of the CDR3 patterns. Oligoclonal patterns consistent with CDR3 restriction were three times more likely in SLE than in controls (OR = 3.7). TCRBV1, BV4, BV5.1, BV7, BV9, BV18 and BV22 gene segment CDR3 patterns of oligoclonality were seen exclusively among lupus patients. HLA-DRB3 increased the risk of oligoclonal expression in SLE. In four patients studied over time, the pattern of TCRBV-CDR3 expression was stable in a second sample obtained 6-14 months later. The increased frequency of CD4+ T cell TCRBV-CDR3 oligoclonal expression in SLE when compared to controls and the persistence of these patterns are consistent with an expanded pool of autoreactive CD4 T cells in SLE which recognize peptides derived from autoantigens. The association of HLA-DRB3 genes with increased risk of CDR3 oligoclonality among the SLE subjects is compatible with the hypothesis that molecules encoded by HLA-DRB3 may facilitate autoantigen recognition by CD4 T cells.
"In T cell-mediated organ-specific autoimmune diseases, such as type 1 diabetes (T1DM), TCR Vβ repertoire analysis, using both spectratyping and flow cytometry, produced conflicting findings [12,13]. In systemic autoimmune diseases, like Systemic Lupus Erythematosus (SLE), TCR Vβ analysis has been conducted in adult populations using the spectratyping method and a marked oligoclonality of the TCR Vβ repertoire has been reported, which is more prominent in patients with active disease [14,15]. It is likely that children with SLE display a similar phenotype, although no data exist regarding the expression of the Vβ chains in the pediatric population. "
[Show abstract][Hide abstract] ABSTRACT: Data regarding the quantitative expression of TCR Vbeta 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 Vbeta 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 Vbeta 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.
CD4 + TCR Vbeta abnormalities (+/- 3SD of controls) were observed mainly in SLE patients. Statistical analysis revealed that the CD4 + Vbeta4 chain was significantly increased in patients with T1DM (p < 0.001), whereas CD4 + Vbeta16 one was significantly increased in SLE patients (p < 0.001) compared to controls.
CD4 + Vbeta4 and CD4 + Vbeta16 chains could be possibly involved in the cascade of events precipitating the pathogenesis of T1DM and SLE in children, respectively.
"At first glance, one can imagine that a condition that leads to the absence of functional Vb18 þ T cells would be unfavorable, because it represents a ''gap'' in the T-cell repertoire. Nevertheless, because Vb18 þ T cells are involved in several autoimmune diseases and other deleterious immune responses (Fraser et al., 1999; Osman et al., 1999; Kircher et al, 2002), in some cases the absence of a given TCR can be advantageous to the individual. In this way, the null TCRBV18 allele could be favored, but its prevalence is too variable at present to suggest a meaningful hypothesis about its frequency. "
[Show abstract][Hide abstract] ABSTRACT: The immune response of relatively small, endogamous populations is of special interest, because they may differ from those of large, ethnically diverse, urban groups. As a contribution to this area of investigation, we tested 99 individuals from two Brazilian native populations for two T-cell receptor gene segments (TCRBV3S1 and TCRBV18) and 241 subjects from eight tribes of this ethnic group in relation to the chemokine receptor CCR5delta32 allele. Differences in TCRBV3S1 and TCRBV18 prevalences of the Amerindians in relation to European- and African-derived individuals were not marked. We confirmed the absence of the CCR5delta32 allele in most groups, its presence in the Mura and Kaingang, probably because of European gene introgression.
American Journal of Human Biology 07/2005; 17(4):515-8. DOI:10.1002/ajhb.20407 · 1.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To compare the accumulated T cell clonotypes in peripheral blood (PB) samples obtained at various times, and the accumulated T cell clonotypes in a PB sample and in an affected kidney, from patients with systemic lupus erythematosus (SLE).
Peripheral blood mononuclear cells (PBMC) were obtained at 2-4 different times from each of 5 SLE patients, with or without flare-up of the disease; in addition, a biopsied kidney tissue sample was obtained from 1 of the patients. RNA was extracted from each sample and complementary DNA was prepared. Genes that encode the variable region of T cell receptor (TCR) B chains (BV) of 3 BV families, 5S1, 8, and 14, were amplified by reverse transcription-polymerase chain reaction (PCR), and the PCR products were cloned for sequencing.
A total of 877 cloned TCR genes was detected in the PBMC samples and the kidney sample. Oligoclonal T cell expansion was detected in 34 of the 36 PCR-amplified BV samples from PBMC (amplification of 3 BV families in 2-4 samples from 5 patients). The composition of clonally expanded T cell clonotypes was relatively stable in the patients with inactive SLE. In contrast, the composition of clonotypes in the PB changed drastically after the patient experienced the active phase of the disease. T cell clonotypes that had accumulated in the kidney appeared to be restricted and distinct from those that had accumulated in the PB of the same patient.
Different T cell clonotypes expand at different times and at different sites in patients with active SLE. The sensitizing antigens may change over the course of the disease and may be different at each site.
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