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Identification of a B cell signature associated with renal transplant tolerance in humans.

Publication ,  Journal Article
Newell, KA; Asare, A; Kirk, AD; Gisler, TD; Bourcier, K; Suthanthiran, M; Burlingham, WJ; Marks, WH; Sanz, I; Lechler, RI; Turka, LA ...
Published in: J Clin Invest
June 2010

Establishing long-term allograft acceptance without the requirement for continuous immunosuppression, a condition known as allograft tolerance, is a highly desirable therapeutic goal in solid organ transplantation. Determining which recipients would benefit from withdrawal or minimization of immunosuppression would be greatly facilitated by biomarkers predictive of tolerance. In this study, we identified the largest reported cohort to our knowledge of tolerant renal transplant recipients, as defined by stable graft function and receiving no immunosuppression for more than 1 year, and compared their gene expression profiles and peripheral blood lymphocyte subsets with those of subjects with stable graft function who are receiving immunosuppressive drugs as well as healthy controls. In addition to being associated with clinical and phenotypic parameters, renal allograft tolerance was strongly associated with a B cell signature using several assays. Tolerant subjects showed increased expression of multiple B cell differentiation genes, and a set of just 3 of these genes distinguished tolerant from nontolerant recipients in a unique test set of samples. This B cell signature was associated with upregulation of CD20 mRNA in urine sediment cells and elevated numbers of peripheral blood naive and transitional B cells in tolerant participants compared with those receiving immunosuppression. These results point to a critical role for B cells in regulating alloimmunity and provide a candidate set of genes for wider-scale screening of renal transplant recipients.

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Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

June 2010

Volume

120

Issue

6

Start / End Page

1836 / 1847

Location

United States

Related Subject Headings

  • Transplantation Tolerance
  • Lymphocyte Activation
  • Kidney Transplantation
  • Immunosuppression Therapy
  • Immunology
  • Immune Tolerance
  • Humans
  • Gene Expression Profiling
  • Biomarkers
  • B-Lymphocytes
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Newell, K. A., Asare, A., Kirk, A. D., Gisler, T. D., Bourcier, K., Suthanthiran, M., … Immune Tolerance Network ST507 Study Group, . (2010). Identification of a B cell signature associated with renal transplant tolerance in humans. J Clin Invest, 120(6), 1836–1847. https://doi.org/10.1172/JCI39933
Newell, Kenneth A., Adam Asare, Allan D. Kirk, Trang D. Gisler, Kasia Bourcier, Manikkam Suthanthiran, William J. Burlingham, et al. “Identification of a B cell signature associated with renal transplant tolerance in humans.J Clin Invest 120, no. 6 (June 2010): 1836–47. https://doi.org/10.1172/JCI39933.
Newell KA, Asare A, Kirk AD, Gisler TD, Bourcier K, Suthanthiran M, et al. Identification of a B cell signature associated with renal transplant tolerance in humans. J Clin Invest. 2010 Jun;120(6):1836–47.
Newell, Kenneth A., et al. “Identification of a B cell signature associated with renal transplant tolerance in humans.J Clin Invest, vol. 120, no. 6, June 2010, pp. 1836–47. Pubmed, doi:10.1172/JCI39933.
Newell KA, Asare A, Kirk AD, Gisler TD, Bourcier K, Suthanthiran M, Burlingham WJ, Marks WH, Sanz I, Lechler RI, Hernandez-Fuentes MP, Turka LA, Seyfert-Margolis VL, Immune Tolerance Network ST507 Study Group. Identification of a B cell signature associated with renal transplant tolerance in humans. J Clin Invest. 2010 Jun;120(6):1836–1847.

Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

June 2010

Volume

120

Issue

6

Start / End Page

1836 / 1847

Location

United States

Related Subject Headings

  • Transplantation Tolerance
  • Lymphocyte Activation
  • Kidney Transplantation
  • Immunosuppression Therapy
  • Immunology
  • Immune Tolerance
  • Humans
  • Gene Expression Profiling
  • Biomarkers
  • B-Lymphocytes