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

作者：Edelbauer Monika^*; Kshirsagar Sudhir; Riedl Magdalena; Billing Heiko; Toenshoff Burkhard; Haffner Dieter; Cortina Gerard; Amon Oliver; Ross Sophia; Doetsch Joerg; Wechselberger Gottfried; Weber Lutz T; Dablander Martin; Anliker Markus; Griesmacher Andrea; Steichen Gersdorf Elisabeth

来源：Journal of Clinical Immunology, 2012, 32(3): 477-487.

DOI：10.1007/s10875-011-9637-0

• Childhood
• cytokines
• lupus nephritis
• effector T cells
• regulatory T cells

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). %26lt;br%26gt;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-gamma was assessed after stimulation with anti-CD3 and anti-CD28. Serum concentrations of IP10, CCL2, TGF-beta, 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). %26lt;br%26gt;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-beta 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). %26lt;br%26gt;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.

• 出版日期2012-6
• 单位河北医科大学