Messenger RNA for FOXP3 in the urine of renal-allograft recipients

Thangamani Muthukumar, Darshana Dadhania, Ruchuang Ding, Catherine Snopkowski, Rubina Naqvi, Jun B. Lee, Choli Hartono, Baogui Li, Vijay K. Sharma, Surya V. Seshan, Sandip Kapur, Wayne W. Hancock, Joseph E. Schwartz, Manikkam Suthanthiran

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: The outcome of renal transplantation after an episode of acute rejection is difficult to predict, even with an allograft biopsy. METHODS: We studied urine specimens from 36 subjects with acute rejection, 18 subjects with chronic allograft nephropathy, and 29 subjects with normal biopsy results. Levels of messenger RNA (mRNA) for FOXP3, a specification and functional factor for regulatory T lymphocytes, and mRNA for CD25, CD3ε, perforin, and 18S ribosomal RNA (rRNA) were measured with a kinetic, quantitative polymerase-chain-reaction assay. We examined associations of mRNA levels with acute rejection, rejection reversal, and graft failure. RESULTS: The log-transformed mean (±SE) ratio of FOXP3 mRNA copies to 18S ribosomal RNA copies was higher in urine from the group with acute rejection (3.8±0.5) than in the group with chronic allograft nephropathy (1.3±0.7) or the group with normal biopsy results (1.6±0.4) (P<0.001 by the Kruskal-Wallis test). FOXP3 mRNA levels were inversely correlated with serum creatinine levels measured at the time of biopsy in the acute-rejection group (Spearman's correlation coefficient =-0.38, P=0.02) but not in the group with chronic allograft nephropathy or the group with normal biopsy results. Analyses of receiver-operating-characteristic curves demonstrated that reversal of acute rejection can be predicted with 90 percent sensitivity and 73 percent specificity with use of the optimal identified cutoff for FOXP3 mRNA of 3.46 (P=0.001). FOXP3 mRNA levels identified subjects at risk for graft failure within six months after the incident episode of acute rejection (relative risk for the lowest third of FOXP3 mRNA levels, 6; P=0.02). None of the other mRNA levels were predictive of reversal of acute rejection or graft failure. CONCLUSIONS: Measurement of FOXP3 mRNA in urine may offer a noninvasive means of improving the prediction of outcome of acute rejection of renal transplants.

Original languageEnglish
Pages (from-to)2342-2351
Number of pages10
JournalNew England Journal of Medicine
Volume353
Issue number22
DOIs
Publication statusPublished - 1 Dec 2005
Externally publishedYes

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Allografts
Urine
Kidney
Messenger RNA
Biopsy
Graft Rejection
Perforin
Regulatory T-Lymphocytes
ROC Curve
Kidney Transplantation
Real-Time Polymerase Chain Reaction
Creatinine
Transplants
Serum

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Muthukumar, T., Dadhania, D., Ding, R., Snopkowski, C., Naqvi, R., Lee, J. B., ... Suthanthiran, M. (2005). Messenger RNA for FOXP3 in the urine of renal-allograft recipients. New England Journal of Medicine, 353(22), 2342-2351. https://doi.org/10.1056/NEJMoa051907

Messenger RNA for FOXP3 in the urine of renal-allograft recipients. / Muthukumar, Thangamani; Dadhania, Darshana; Ding, Ruchuang; Snopkowski, Catherine; Naqvi, Rubina; Lee, Jun B.; Hartono, Choli; Li, Baogui; Sharma, Vijay K.; Seshan, Surya V.; Kapur, Sandip; Hancock, Wayne W.; Schwartz, Joseph E.; Suthanthiran, Manikkam.

In: New England Journal of Medicine, Vol. 353, No. 22, 01.12.2005, p. 2342-2351.

Research output: Contribution to journalArticle

Muthukumar, T, Dadhania, D, Ding, R, Snopkowski, C, Naqvi, R, Lee, JB, Hartono, C, Li, B, Sharma, VK, Seshan, SV, Kapur, S, Hancock, WW, Schwartz, JE & Suthanthiran, M 2005, 'Messenger RNA for FOXP3 in the urine of renal-allograft recipients', New England Journal of Medicine, vol. 353, no. 22, pp. 2342-2351. https://doi.org/10.1056/NEJMoa051907
Muthukumar T, Dadhania D, Ding R, Snopkowski C, Naqvi R, Lee JB et al. Messenger RNA for FOXP3 in the urine of renal-allograft recipients. New England Journal of Medicine. 2005 Dec 1;353(22):2342-2351. https://doi.org/10.1056/NEJMoa051907
Muthukumar, Thangamani ; Dadhania, Darshana ; Ding, Ruchuang ; Snopkowski, Catherine ; Naqvi, Rubina ; Lee, Jun B. ; Hartono, Choli ; Li, Baogui ; Sharma, Vijay K. ; Seshan, Surya V. ; Kapur, Sandip ; Hancock, Wayne W. ; Schwartz, Joseph E. ; Suthanthiran, Manikkam. / Messenger RNA for FOXP3 in the urine of renal-allograft recipients. In: New England Journal of Medicine. 2005 ; Vol. 353, No. 22. pp. 2342-2351.
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abstract = "BACKGROUND: The outcome of renal transplantation after an episode of acute rejection is difficult to predict, even with an allograft biopsy. METHODS: We studied urine specimens from 36 subjects with acute rejection, 18 subjects with chronic allograft nephropathy, and 29 subjects with normal biopsy results. Levels of messenger RNA (mRNA) for FOXP3, a specification and functional factor for regulatory T lymphocytes, and mRNA for CD25, CD3ε, perforin, and 18S ribosomal RNA (rRNA) were measured with a kinetic, quantitative polymerase-chain-reaction assay. We examined associations of mRNA levels with acute rejection, rejection reversal, and graft failure. RESULTS: The log-transformed mean (±SE) ratio of FOXP3 mRNA copies to 18S ribosomal RNA copies was higher in urine from the group with acute rejection (3.8±0.5) than in the group with chronic allograft nephropathy (1.3±0.7) or the group with normal biopsy results (1.6±0.4) (P<0.001 by the Kruskal-Wallis test). FOXP3 mRNA levels were inversely correlated with serum creatinine levels measured at the time of biopsy in the acute-rejection group (Spearman's correlation coefficient =-0.38, P=0.02) but not in the group with chronic allograft nephropathy or the group with normal biopsy results. Analyses of receiver-operating-characteristic curves demonstrated that reversal of acute rejection can be predicted with 90 percent sensitivity and 73 percent specificity with use of the optimal identified cutoff for FOXP3 mRNA of 3.46 (P=0.001). FOXP3 mRNA levels identified subjects at risk for graft failure within six months after the incident episode of acute rejection (relative risk for the lowest third of FOXP3 mRNA levels, 6; P=0.02). None of the other mRNA levels were predictive of reversal of acute rejection or graft failure. CONCLUSIONS: Measurement of FOXP3 mRNA in urine may offer a noninvasive means of improving the prediction of outcome of acute rejection of renal transplants.",
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AU - Muthukumar, Thangamani

AU - Dadhania, Darshana

AU - Ding, Ruchuang

AU - Snopkowski, Catherine

AU - Naqvi, Rubina

AU - Lee, Jun B.

AU - Hartono, Choli

AU - Li, Baogui

AU - Sharma, Vijay K.

AU - Seshan, Surya V.

AU - Kapur, Sandip

AU - Hancock, Wayne W.

AU - Schwartz, Joseph E.

AU - Suthanthiran, Manikkam

PY - 2005/12/1

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N2 - BACKGROUND: The outcome of renal transplantation after an episode of acute rejection is difficult to predict, even with an allograft biopsy. METHODS: We studied urine specimens from 36 subjects with acute rejection, 18 subjects with chronic allograft nephropathy, and 29 subjects with normal biopsy results. Levels of messenger RNA (mRNA) for FOXP3, a specification and functional factor for regulatory T lymphocytes, and mRNA for CD25, CD3ε, perforin, and 18S ribosomal RNA (rRNA) were measured with a kinetic, quantitative polymerase-chain-reaction assay. We examined associations of mRNA levels with acute rejection, rejection reversal, and graft failure. RESULTS: The log-transformed mean (±SE) ratio of FOXP3 mRNA copies to 18S ribosomal RNA copies was higher in urine from the group with acute rejection (3.8±0.5) than in the group with chronic allograft nephropathy (1.3±0.7) or the group with normal biopsy results (1.6±0.4) (P<0.001 by the Kruskal-Wallis test). FOXP3 mRNA levels were inversely correlated with serum creatinine levels measured at the time of biopsy in the acute-rejection group (Spearman's correlation coefficient =-0.38, P=0.02) but not in the group with chronic allograft nephropathy or the group with normal biopsy results. Analyses of receiver-operating-characteristic curves demonstrated that reversal of acute rejection can be predicted with 90 percent sensitivity and 73 percent specificity with use of the optimal identified cutoff for FOXP3 mRNA of 3.46 (P=0.001). FOXP3 mRNA levels identified subjects at risk for graft failure within six months after the incident episode of acute rejection (relative risk for the lowest third of FOXP3 mRNA levels, 6; P=0.02). None of the other mRNA levels were predictive of reversal of acute rejection or graft failure. CONCLUSIONS: Measurement of FOXP3 mRNA in urine may offer a noninvasive means of improving the prediction of outcome of acute rejection of renal transplants.

AB - BACKGROUND: The outcome of renal transplantation after an episode of acute rejection is difficult to predict, even with an allograft biopsy. METHODS: We studied urine specimens from 36 subjects with acute rejection, 18 subjects with chronic allograft nephropathy, and 29 subjects with normal biopsy results. Levels of messenger RNA (mRNA) for FOXP3, a specification and functional factor for regulatory T lymphocytes, and mRNA for CD25, CD3ε, perforin, and 18S ribosomal RNA (rRNA) were measured with a kinetic, quantitative polymerase-chain-reaction assay. We examined associations of mRNA levels with acute rejection, rejection reversal, and graft failure. RESULTS: The log-transformed mean (±SE) ratio of FOXP3 mRNA copies to 18S ribosomal RNA copies was higher in urine from the group with acute rejection (3.8±0.5) than in the group with chronic allograft nephropathy (1.3±0.7) or the group with normal biopsy results (1.6±0.4) (P<0.001 by the Kruskal-Wallis test). FOXP3 mRNA levels were inversely correlated with serum creatinine levels measured at the time of biopsy in the acute-rejection group (Spearman's correlation coefficient =-0.38, P=0.02) but not in the group with chronic allograft nephropathy or the group with normal biopsy results. Analyses of receiver-operating-characteristic curves demonstrated that reversal of acute rejection can be predicted with 90 percent sensitivity and 73 percent specificity with use of the optimal identified cutoff for FOXP3 mRNA of 3.46 (P=0.001). FOXP3 mRNA levels identified subjects at risk for graft failure within six months after the incident episode of acute rejection (relative risk for the lowest third of FOXP3 mRNA levels, 6; P=0.02). None of the other mRNA levels were predictive of reversal of acute rejection or graft failure. CONCLUSIONS: Measurement of FOXP3 mRNA in urine may offer a noninvasive means of improving the prediction of outcome of acute rejection of renal transplants.

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