Volume 9 Supplement 2

6th European Workshop on Immune-Mediated Inflammatory Diseases

Open Access

Active regulatory T-cells contribute to broadened T-cell repertoire diversity in ivIg-treated SLE patients

  • Nuno Costa1,
  • Ana E Pires2,
  • Ana M Gabriel1,
  • Luiz F Goulart1,
  • Clara Pereira1, 3,
  • Barbara Leal3,
  • Ana C Queiros2,
  • Wahiba Chaara4,
  • Maria F Moraes-Fontes1, 6,
  • Carlos Vasconcelos5,
  • Carlos Ferreira6,
  • Jorge Martins7,
  • Marina Bastos8,
  • Maria J Santos9,
  • Maria A Pereira10,
  • Berta Martins3,
  • Margarida Lima5,
  • Cristina João2,
  • Adrien Six4,
  • Jocelyne Demengeot1 and
  • Constantin Fesel1
Journal of Translational Medicine20119(Suppl 2):P6

https://doi.org/10.1186/1479-5876-9-S2-P6

Published: 23 November 2011

Intravenous IgG (ivIg) is a therapeutic alternative for lupus erythematosus. Relative oligoclonality of circulating T-cells in SLE has been reported. Also CD4+Foxp3+ regulatory T-cells (Tregs) have a characteristically reduced activity in SLE, reflected by CD25 surface density. Aiming to study the role of Tregs for ivIg therapy, we characterized Tregs and determined TCR spectratypes of four Vb families with reported oligoclonality, in 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, 11 responded with clinical improvement. 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 Vb-familywise repertoire perturbation, calculated for each patient in respect to an individual reference profile averaged over all available time points. For 11/15 patients, average Vb1/Vb2/Vb11/Vb14 repertoires were less perturbed under ivIg treatment 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, other than Treg/CD4+ frequency, 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 Vb11 and Vb14 perturbations measured under ivIg therapy, which indicates a role of active Tregs in the therapeutic effect of ivIg.

Declarations

Acknowledgements

This work was supported by Octapharma.

Authors’ Affiliations

(1)
Instituto Gulbenkian de Ciência
(2)
IPO-CIPM/CEDOC-FCM
(3)
ICBAS
(4)
UPMC-Paris-6/CNRS-UMR7211/AP-HP
(5)
Hospital Sto-António
(6)
Hospital Sta-Maria
(7)
Hospital Marmeleiros
(8)
Hospital São-Teotónio
(9)
Hospital Garcia de Orta
(10)
Hospital de Faro

Copyright

© Costa et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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