Broadened T-cell repertoire diversity in ivIg-treated SLE patients is also related to the individual status of regulatory T-cells

Nuno Costa, Ana E. Pires, Ana M. Gabriel, Luiz F. Goulart, Clara Pereira, Bárbara Leal, Ana C. Queiros, Wahiba Chaara, Maria F. Moraes-Fontes, Carlos Vasconcelos, Carlos Ferreira, Jorge Martins, Marina Bastos, Maria J. Santos, Maria A. Pereira, Berta Martins, Margarida Lima, Cristina João, Adrien Six, Jocelyne Demengeot & 1 others Constantin Fesel

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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.

Original languageEnglish
Pages (from-to)349-360
Number of pages12
JournalJournal Of Clinical Immunology
Volume33
Issue number2
DOIs
Publication statusPublished - 1 Jan 2013

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Regulatory T-Lymphocytes
Immunoglobulin G
T-Lymphocytes
Therapeutics
Therapeutic Uses
Longitudinal Studies
Cell Count
Phenotype

Keywords

  • Autoimmunity
  • CD25
  • Intravenous IgG
  • Regulatory T-cells
  • Systemic lupus erythematosus
  • TCR spectratypes

Cite this

Costa, Nuno ; Pires, Ana E. ; Gabriel, Ana M. ; Goulart, Luiz F. ; Pereira, Clara ; Leal, Bárbara ; Queiros, Ana C. ; Chaara, Wahiba ; Moraes-Fontes, Maria F. ; Vasconcelos, Carlos ; Ferreira, Carlos ; Martins, Jorge ; Bastos, Marina ; Santos, Maria J. ; Pereira, Maria A. ; Martins, Berta ; Lima, Margarida ; João, Cristina ; Six, Adrien ; Demengeot, Jocelyne ; Fesel, Constantin. / Broadened T-cell repertoire diversity in ivIg-treated SLE patients is also related to the individual status of regulatory T-cells. In: Journal Of Clinical Immunology. 2013 ; Vol. 33, No. 2. pp. 349-360.
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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.",
keywords = "Autoimmunity, CD25, Intravenous IgG, Regulatory T-cells, Systemic lupus erythematosus, TCR spectratypes",
author = "Nuno Costa and Pires, {Ana E.} and Gabriel, {Ana M.} and Goulart, {Luiz F.} and Clara Pereira and B{\'a}rbara Leal and Queiros, {Ana C.} and Wahiba Chaara and Moraes-Fontes, {Maria F.} and Carlos Vasconcelos and Carlos Ferreira and Jorge Martins and Marina Bastos and Santos, {Maria J.} and Pereira, {Maria A.} and Berta Martins and Margarida Lima and Cristina Jo{\~a}o and Adrien Six and Jocelyne Demengeot and Constantin Fesel",
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Costa, N, Pires, AE, Gabriel, AM, Goulart, LF, Pereira, C, Leal, B, Queiros, AC, Chaara, W, Moraes-Fontes, MF, Vasconcelos, C, Ferreira, C, Martins, J, Bastos, M, Santos, MJ, Pereira, MA, Martins, B, Lima, M, João, C, Six, A, Demengeot, J & Fesel, C 2013, 'Broadened T-cell repertoire diversity in ivIg-treated SLE patients is also related to the individual status of regulatory T-cells', Journal Of Clinical Immunology, vol. 33, no. 2, pp. 349-360. https://doi.org/10.1007/s10875-012-9816-7

Broadened T-cell repertoire diversity in ivIg-treated SLE patients is also related to the individual status of regulatory T-cells. / Costa, Nuno; Pires, Ana E.; Gabriel, Ana M.; Goulart, Luiz F.; Pereira, Clara; Leal, Bárbara; Queiros, Ana C.; Chaara, Wahiba; Moraes-Fontes, Maria F.; Vasconcelos, Carlos; Ferreira, Carlos; Martins, Jorge; Bastos, Marina; Santos, Maria J.; Pereira, Maria A.; Martins, Berta; Lima, Margarida; João, Cristina; Six, Adrien; Demengeot, Jocelyne; Fesel, Constantin.

In: Journal Of Clinical Immunology, Vol. 33, No. 2, 01.01.2013, p. 349-360.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Broadened T-cell repertoire diversity in ivIg-treated SLE patients is also related to the individual status of regulatory T-cells

AU - Costa, Nuno

AU - Pires, Ana E.

AU - Gabriel, Ana M.

AU - Goulart, Luiz F.

AU - Pereira, Clara

AU - Leal, Bárbara

AU - Queiros, Ana C.

AU - Chaara, Wahiba

AU - Moraes-Fontes, Maria F.

AU - Vasconcelos, Carlos

AU - Ferreira, Carlos

AU - Martins, Jorge

AU - Bastos, Marina

AU - Santos, Maria J.

AU - Pereira, Maria A.

AU - Martins, Berta

AU - Lima, Margarida

AU - João, Cristina

AU - Six, Adrien

AU - Demengeot, Jocelyne

AU - Fesel, Constantin

PY - 2013/1/1

Y1 - 2013/1/1

N2 - 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.

AB - 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.

KW - Autoimmunity

KW - CD25

KW - Intravenous IgG

KW - Regulatory T-cells

KW - Systemic lupus erythematosus

KW - TCR spectratypes

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U2 - 10.1007/s10875-012-9816-7

DO - 10.1007/s10875-012-9816-7

M3 - Article

VL - 33

SP - 349

EP - 360

JO - Journal Of Clinical Immunology

JF - Journal Of Clinical Immunology

SN - 0271-9142

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