Prolonged expression of CD154 on CD4 T cells from pediatric lupus patients correlates with increased CD154 transcription, increased nuclear factor of activated T cell activity, and glomerulonephritis

Jay Mehta, Anna Genin, Michael Brunner, Lisabeth V. Scalzi, Nilamadhab Mishra, Timothy Beukelman, Randy Q. Cron

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Objective. To assess CD154 expression in patients with pediatric systemic lupus erythematosus (SLE) and to explore a transcriptional mechanism that may explain dysregulated expression of CD154. Methods. Cell surface CD154 expression (preand postactivation) in peripheral blood CD4 T cells from 29 children with lupus and 29 controls matched for age, sex, and ethnicity was examined by flow cytometry. CD154 expression was correlated with clinical features, laboratory parameters, and treatments received. Increased CD154 expression on CD4 T cells from the SLE patients was correlated with CD154 message and transcription rates by real-time reverse transcription-polymerase chain reaction (RT-PCR) and nuclear run-on assays, respectively. Nuclear factor of activated T cell (NF-AT) transcription activity and mRNA levels in CD4 T cells from SLE patients were explored by reporter gene analysis and real-time RT-PCR, respectively. Results. CD154 surface protein levels were increased 1.44-fold in CD4 T cells from SLE patients as compared with controls in cells evaluated 1 day postactivation ex vivo. This increase correlated clinically with the presence of nephritis and an elevated erythrocyte sedimentation rate. Increased CD154 protein levels also correlated with increased CD154 mRNA levels and with CD154 transcription rates, particularly at later time points following T cell activation. Reporter gene analyses revealed a trend for increased NF-AT, but decreased activator protein 1 and similar NF-κB, activity in CD4 T cells from SLE patients as compared with controls. Moreover, NF-AT1 and, in particular, NF-AT2 mRNA levels were notably increased in CD4 T cells from SLE patients as compared with controls. Conclusion. Following activation, cell surface CD154 is increased on CD4 T cells from pediatric lupus patients as compared with controls, and this increase correlates with the presence of nephritis, increased CD154 transcription rates, and increased NF-AT activity. These results suggest that NF-AT/calcineurin inhibitors, such as tacrolimus and cyclosporine, may be beneficial in the treatment of lupus nephritis.

Original languageEnglish (US)
Pages (from-to)2499-2509
Number of pages11
JournalArthritis and rheumatism
Volume62
Issue number8
DOIs
StatePublished - Aug 1 2010

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NFATC Transcription Factors
Glomerulonephritis
Systemic Lupus Erythematosus
Pediatrics
T-Lymphocytes
Nephritis
Reporter Genes
Messenger RNA
Reverse Transcription
Polymerase Chain Reaction
Lupus Nephritis
Blood Sedimentation
Transcription Factor AP-1
Tacrolimus
Cyclosporine
Flow Cytometry
Membrane Proteins

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

Cite this

@article{ffbd4effe3514793a62eb5b02b3937ec,
title = "Prolonged expression of CD154 on CD4 T cells from pediatric lupus patients correlates with increased CD154 transcription, increased nuclear factor of activated T cell activity, and glomerulonephritis",
abstract = "Objective. To assess CD154 expression in patients with pediatric systemic lupus erythematosus (SLE) and to explore a transcriptional mechanism that may explain dysregulated expression of CD154. Methods. Cell surface CD154 expression (preand postactivation) in peripheral blood CD4 T cells from 29 children with lupus and 29 controls matched for age, sex, and ethnicity was examined by flow cytometry. CD154 expression was correlated with clinical features, laboratory parameters, and treatments received. Increased CD154 expression on CD4 T cells from the SLE patients was correlated with CD154 message and transcription rates by real-time reverse transcription-polymerase chain reaction (RT-PCR) and nuclear run-on assays, respectively. Nuclear factor of activated T cell (NF-AT) transcription activity and mRNA levels in CD4 T cells from SLE patients were explored by reporter gene analysis and real-time RT-PCR, respectively. Results. CD154 surface protein levels were increased 1.44-fold in CD4 T cells from SLE patients as compared with controls in cells evaluated 1 day postactivation ex vivo. This increase correlated clinically with the presence of nephritis and an elevated erythrocyte sedimentation rate. Increased CD154 protein levels also correlated with increased CD154 mRNA levels and with CD154 transcription rates, particularly at later time points following T cell activation. Reporter gene analyses revealed a trend for increased NF-AT, but decreased activator protein 1 and similar NF-κB, activity in CD4 T cells from SLE patients as compared with controls. Moreover, NF-AT1 and, in particular, NF-AT2 mRNA levels were notably increased in CD4 T cells from SLE patients as compared with controls. Conclusion. Following activation, cell surface CD154 is increased on CD4 T cells from pediatric lupus patients as compared with controls, and this increase correlates with the presence of nephritis, increased CD154 transcription rates, and increased NF-AT activity. These results suggest that NF-AT/calcineurin inhibitors, such as tacrolimus and cyclosporine, may be beneficial in the treatment of lupus nephritis.",
author = "Jay Mehta and Anna Genin and Michael Brunner and Scalzi, {Lisabeth V.} and Nilamadhab Mishra and Timothy Beukelman and Cron, {Randy Q.}",
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Prolonged expression of CD154 on CD4 T cells from pediatric lupus patients correlates with increased CD154 transcription, increased nuclear factor of activated T cell activity, and glomerulonephritis. / Mehta, Jay; Genin, Anna; Brunner, Michael; Scalzi, Lisabeth V.; Mishra, Nilamadhab; Beukelman, Timothy; Cron, Randy Q.

In: Arthritis and rheumatism, Vol. 62, No. 8, 01.08.2010, p. 2499-2509.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Prolonged expression of CD154 on CD4 T cells from pediatric lupus patients correlates with increased CD154 transcription, increased nuclear factor of activated T cell activity, and glomerulonephritis

AU - Mehta, Jay

AU - Genin, Anna

AU - Brunner, Michael

AU - Scalzi, Lisabeth V.

AU - Mishra, Nilamadhab

AU - Beukelman, Timothy

AU - Cron, Randy Q.

PY - 2010/8/1

Y1 - 2010/8/1

N2 - Objective. To assess CD154 expression in patients with pediatric systemic lupus erythematosus (SLE) and to explore a transcriptional mechanism that may explain dysregulated expression of CD154. Methods. Cell surface CD154 expression (preand postactivation) in peripheral blood CD4 T cells from 29 children with lupus and 29 controls matched for age, sex, and ethnicity was examined by flow cytometry. CD154 expression was correlated with clinical features, laboratory parameters, and treatments received. Increased CD154 expression on CD4 T cells from the SLE patients was correlated with CD154 message and transcription rates by real-time reverse transcription-polymerase chain reaction (RT-PCR) and nuclear run-on assays, respectively. Nuclear factor of activated T cell (NF-AT) transcription activity and mRNA levels in CD4 T cells from SLE patients were explored by reporter gene analysis and real-time RT-PCR, respectively. Results. CD154 surface protein levels were increased 1.44-fold in CD4 T cells from SLE patients as compared with controls in cells evaluated 1 day postactivation ex vivo. This increase correlated clinically with the presence of nephritis and an elevated erythrocyte sedimentation rate. Increased CD154 protein levels also correlated with increased CD154 mRNA levels and with CD154 transcription rates, particularly at later time points following T cell activation. Reporter gene analyses revealed a trend for increased NF-AT, but decreased activator protein 1 and similar NF-κB, activity in CD4 T cells from SLE patients as compared with controls. Moreover, NF-AT1 and, in particular, NF-AT2 mRNA levels were notably increased in CD4 T cells from SLE patients as compared with controls. Conclusion. Following activation, cell surface CD154 is increased on CD4 T cells from pediatric lupus patients as compared with controls, and this increase correlates with the presence of nephritis, increased CD154 transcription rates, and increased NF-AT activity. These results suggest that NF-AT/calcineurin inhibitors, such as tacrolimus and cyclosporine, may be beneficial in the treatment of lupus nephritis.

AB - Objective. To assess CD154 expression in patients with pediatric systemic lupus erythematosus (SLE) and to explore a transcriptional mechanism that may explain dysregulated expression of CD154. Methods. Cell surface CD154 expression (preand postactivation) in peripheral blood CD4 T cells from 29 children with lupus and 29 controls matched for age, sex, and ethnicity was examined by flow cytometry. CD154 expression was correlated with clinical features, laboratory parameters, and treatments received. Increased CD154 expression on CD4 T cells from the SLE patients was correlated with CD154 message and transcription rates by real-time reverse transcription-polymerase chain reaction (RT-PCR) and nuclear run-on assays, respectively. Nuclear factor of activated T cell (NF-AT) transcription activity and mRNA levels in CD4 T cells from SLE patients were explored by reporter gene analysis and real-time RT-PCR, respectively. Results. CD154 surface protein levels were increased 1.44-fold in CD4 T cells from SLE patients as compared with controls in cells evaluated 1 day postactivation ex vivo. This increase correlated clinically with the presence of nephritis and an elevated erythrocyte sedimentation rate. Increased CD154 protein levels also correlated with increased CD154 mRNA levels and with CD154 transcription rates, particularly at later time points following T cell activation. Reporter gene analyses revealed a trend for increased NF-AT, but decreased activator protein 1 and similar NF-κB, activity in CD4 T cells from SLE patients as compared with controls. Moreover, NF-AT1 and, in particular, NF-AT2 mRNA levels were notably increased in CD4 T cells from SLE patients as compared with controls. Conclusion. Following activation, cell surface CD154 is increased on CD4 T cells from pediatric lupus patients as compared with controls, and this increase correlates with the presence of nephritis, increased CD154 transcription rates, and increased NF-AT activity. These results suggest that NF-AT/calcineurin inhibitors, such as tacrolimus and cyclosporine, may be beneficial in the treatment of lupus nephritis.

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