Broadened T-cell Repertoire Diversity in ivIg-treated SLE Patients is Also Related to the Individual Status of Regulatory T-cells

• Type: Article in International Scientific Journal
• Date: 2013

Authors

Costa, N (Author) Other; Pires, AE (Author) Other; Gabriel, AM (Author) Other; Goulart, LF (Author) Other; Pereira, C (Author) Other; Leal, B (Author) Other; Queiros, AC (Author) Other; Chaara, W (Author) Other; Moraes Fontes, MF (Author) Other; Carlos Vasconcelos (Author) ICBAS; Ferreira, C (Author) Other; Martins, J (Author) Other; Bastos, M (Author) Other; Santos, MJ (Author) Other; Pereira, MA (Author) Other; Martins, B (Author) Other; Lima, M (Author) ICBAS; Joao, C (Author) Other; Six, A (Author) Other; Demengeot, J (Author) Other; Fesel, C (Author) Other

Journal

Title: Journal of Clinical Immunology

Vol. 33

Pages: 349-360

ISSN: 0271-9142

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 13 Citations

Scopus - 15 Citations

Other information

Authenticus ID: P-006-EEJ

DOI: 10.1007/s10875-012-9816-7

Abstract (EN): 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 V beta 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 V beta-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 V beta 1/V beta 2/V beta 11/V beta 14 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 V beta 11 and V beta 14 perturbations measured under ivIg therapy. Conclusions This indicates a role of active Tregs in the therapeutic effect of ivIg.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12