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Erschienen in:

01.06.2012

Activity of Childhood Lupus Nephritis is Linked to Altered T Cell and Cytokine Homeostasis

verfasst von: Monika Edelbauer, Sudhir Kshirsagar, Magdalena Riedl, Heiko Billing, Burkhard Tönshoff, Dieter Haffner, Gerard Cortina, Oliver Amon, Sophia Ross, Jörg Dötsch, Gottfried Wechselberger, Lutz T. Weber, Martin Dablander, Markus Anliker, Andrea Griesmacher, Elisabeth Steichen-Gersdorf

Erschienen in: Journal of Clinical Immunology | Ausgabe 3/2012

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Abstract

Purpose

Standard therapy for lupus nephritis is based on non-specific immunosuppression. We aimed to identify specific alterations in T cell and cytokine homeostasis and possible associations with disease activity in children with lupus nephritis (LN).

Methods

The phenotype of circulating T cells from children with LN and healthy controls (HC) was analyzed by flow cytometry. Intracellular expression of IL-17 and INF-γ was assessed after stimulation with anti-CD3 and anti-CD28. Serum concentrations of IP10, CCL2, TGF-β, IL-17, and IL-23 were measured by ELISA. Disease activity was determined using the Systemic Lupus Erythematosus Disease Activity Index 2000 update (SLEDAI-2K).

Results

Children with active LN displayed increased frequencies of effector memory CD4⁺CD45RO⁺CCR7⁻ and terminal differentiated CD4⁺CD45RA⁺CCR7⁻ T cells and reduced naive CD4⁺CD45RA⁺CCR7⁺ T cells compared to those with inactive LN or HC. Circulating CD4⁺CXCR3⁺ and CD4⁺CCR2⁺ T cells correlated inversely with the renal SLEDAI-2K, whereas IP10 and CCL2 showed a positive correlation. Reduced CD4⁺Foxp3⁺ T cells and serum TFG-β levels in active LN were associated with high serum IL-17 and IL-23 levels and correlated inversely with the renal SLEDAI-2K (r = −0.5855, p = 0.0013 and r = −0.6246, p = 0.0005, respectively), whereas IL-17 and IL-23 correlated positively (r = 0.5516, p = 0.0029 and r = 0.6116, p = 0.0007, respectively). Expansion of Th17 and Th1/Th17 cells in children with LN was significantly greater than in HC (p = 0.0304 and p = 0.0067, respectively).

Conclusion

Children with active LN display high levels of pro-inflammatory cytokines associated with an increase in effector T cells and reduction of regulatory T cells. Therapeutic regulation of the aberrant cytokine profile might specifically interrupt pathogenic mechanisms.

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Titel: Activity of Childhood Lupus Nephritis is Linked to Altered T Cell and Cytokine Homeostasis
verfasst von: Monika Edelbauer
Sudhir Kshirsagar
Magdalena Riedl
Heiko Billing
Burkhard Tönshoff
Dieter Haffner
Gerard Cortina
Oliver Amon
Sophia Ross
Jörg Dötsch
Gottfried Wechselberger
Lutz T. Weber
Martin Dablander
Markus Anliker
Andrea Griesmacher
Elisabeth Steichen-Gersdorf
Publikationsdatum: 01.06.2012
Verlag: Springer US
Erschienen in: Journal of Clinical Immunology / Ausgabe 3/2012
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-011-9637-0

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