Broadened T-cell repertoire diversity in ivIg-treated SLE patients is also related to the individual status of regulatory T-cells.
OBJECTIVE
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.
Instituto Gulbenkian de Ciência, Apartado 14, 2781-901, Oeiras, Portugal.
Nuno
N
Costa
Ana E
AE
Pires
Ana M
AM
Gabriel
Luiz F
LF
Goulart
Clara
C
Pereira
Bárbara
B
Leal
Ana C
AC
Queiros
Wahiba
W
Chaara
Maria F
MF
Moraes-Fontes
Carlos
C
Vasconcelos
Carlos
C
Ferreira
Jorge
J
Martins
Marina
M
Bastos
Maria J
MJ
Santos
Maria A
MA
Pereira
Berta
B
Martins
Margarida
M
Lima
Cristina
C
João
Adrien
A
Six
Jocelyne
J
Demengeot
Constantin
C
Fesel
D000328:Adult; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D016756:Immunoglobulins, Intravenous; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008137:Longitudinal Studies; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000628:therapy*; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016756:Immunoglobulins, Intravenous; D053645:Interleukin-2 Receptor alpha Subunit; D016693:Receptors, Antigen, T-Cell, alpha-beta