CD4 TCRBV CDR3 analysis in prevalent SLE cases from two ethnic groups.
ABSTRACT 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.
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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.BMC Immunology 08/2013; 14(1):33. · 2.61 Impact Factor
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ABSTRACT: PURPOSE: Intravenous IgG (ivIg) is a therapeutic alternative for lupus erythematosus, the mechanism of which remains to be fully understood. Here we investigated whether ivIg affects two established sub-phenotypes of SLE, namely relative oligoclonality of circulating T-cells and reduced activity of CD4 + Foxp3+ regulatory T-cells (Tregs) reflected by lower CD25 surface density. METHODS: We conducted a longitudinal study of 15 lupus patients (14 with SLE and one with discoid LE) treated with ivIg in cycles of 2-6 consecutive monthly infusions. Among these 15 patients, 10 responded to ivIg therapy with clear clinical improvement. We characterized Tregs and determined TCR spectratypes of four Vβ families with reported oligoclonality. Cell counts, cytometry and TCR spectratypes were obtained from peripheral blood at various time points before, during and after ivIg treatment. T-cell oligoclonality was assessed as Vβ-familywise repertoire perturbation, calculated for each patient in respect to an individual reference profile averaged over all available time points. RESULTS: For 11 out of 15 patients, average Vβ1/Vβ2/Vβ11/Vβ14 repertoires were less perturbed under than outside ivIg therapy. The four exceptions with relatively increased average perturbation during ivIg therapy included three patients who failed to respond clinically to an ivIg therapy cycle. Patients' Treg CD25 surface density (cytometric MFI) was clearly reduced when compared to healthy controls, but not obviously influenced by ivIg. However, patients' average Treg CD25 MFI was found negatively correlated with both Vβ11 and Vβ14 perturbations measured under ivIg therapy. CONCLUSIONS: This indicates a role of active Tregs in the therapeutic effect of ivIg.Journal of Clinical Immunology 10/2012; · 3.38 Impact Factor
- Journal of Translational Medicine 11/2011; 9(2). · 3.46 Impact Factor