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Auto- and alloimmune reactivity to human islet allografts transplanted into type 1 diabetic patients

Roep, Bart O. ; Stobbe, Inge ; Duinkerken, Gaby ; Van Rood, Jon J. ; Lernmark, Åke LU orcid ; Keymeulen, Bart ; Pipeleers, Danny ; Claas, Frans H.J. and De Vries, René R.P. (1999) In Diabetes 48(3). p.484-490
Abstract

Allogeneic islet transplantation can restore an insulin-independent state in C-peptide-negative type 1 diabetic patients. We recently reported three cases of surviving islet allografts that were implanted in type 1 diabetic patients under maintenance immune suppression for a previous kidney graft. The present study compares islet graft-specific cellular auto- and alloreactivity in peripheral blood from those three recipients and from four patients with failing islet allografts measured over a period of 6 months after portal islet implantation. The three cases that remained C-peptide- positive for >1 year exhibited no signs of alloreactivity, and their autoreactivity to islet autoantigens was only marginally increased. In contrast,... (More)

Allogeneic islet transplantation can restore an insulin-independent state in C-peptide-negative type 1 diabetic patients. We recently reported three cases of surviving islet allografts that were implanted in type 1 diabetic patients under maintenance immune suppression for a previous kidney graft. The present study compares islet graft-specific cellular auto- and alloreactivity in peripheral blood from those three recipients and from four patients with failing islet allografts measured over a period of 6 months after portal islet implantation. The three cases that remained C-peptide- positive for >1 year exhibited no signs of alloreactivity, and their autoreactivity to islet autoantigens was only marginally increased. In contrast, rapid failure (<3 weeks) in three other cases was accompanied by increases in precursor frequencies of graft-specific alloreactive T-cells; in one of them, the alloreactivity was preceded by a sharply increased autoreactivity to several islet autoantigens. One recipient had a delayed loss of islet graft function (33 weeks); he did not exhibit signs of graft- specific alloimmunity, but developed a delayed increase in autoreactivity. The parallel between metabolic outcome of human β-cell allografts and cellular auto- and alloreactivity in peripheral blood suggests a causal relationship. The present study therefore demonstrates that T-cell reactivities in peripheral blood can be used to monitor immune mechanisms, which influence survival of β-cell allografts in diabetic patients.

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author
; ; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
in
Diabetes
volume
48
issue
3
pages
484 - 490
publisher
American Diabetes Association Inc.
external identifiers
  • pmid:10078547
  • scopus:0032971910
ISSN
0012-1797
DOI
10.2337/diabetes.48.3.484
language
English
LU publication?
no
id
1120639d-edb4-46a8-ab1d-d4bbfffaf346
date added to LUP
2019-06-30 23:31:22
date last changed
2024-03-13 08:07:27
@article{1120639d-edb4-46a8-ab1d-d4bbfffaf346,
  abstract     = {{<p>Allogeneic islet transplantation can restore an insulin-independent state in C-peptide-negative type 1 diabetic patients. We recently reported three cases of surviving islet allografts that were implanted in type 1 diabetic patients under maintenance immune suppression for a previous kidney graft. The present study compares islet graft-specific cellular auto- and alloreactivity in peripheral blood from those three recipients and from four patients with failing islet allografts measured over a period of 6 months after portal islet implantation. The three cases that remained C-peptide- positive for &gt;1 year exhibited no signs of alloreactivity, and their autoreactivity to islet autoantigens was only marginally increased. In contrast, rapid failure (&lt;3 weeks) in three other cases was accompanied by increases in precursor frequencies of graft-specific alloreactive T-cells; in one of them, the alloreactivity was preceded by a sharply increased autoreactivity to several islet autoantigens. One recipient had a delayed loss of islet graft function (33 weeks); he did not exhibit signs of graft- specific alloimmunity, but developed a delayed increase in autoreactivity. The parallel between metabolic outcome of human β-cell allografts and cellular auto- and alloreactivity in peripheral blood suggests a causal relationship. The present study therefore demonstrates that T-cell reactivities in peripheral blood can be used to monitor immune mechanisms, which influence survival of β-cell allografts in diabetic patients.</p>}},
  author       = {{Roep, Bart O. and Stobbe, Inge and Duinkerken, Gaby and Van Rood, Jon J. and Lernmark, Åke and Keymeulen, Bart and Pipeleers, Danny and Claas, Frans H.J. and De Vries, René R.P.}},
  issn         = {{0012-1797}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{3}},
  pages        = {{484--490}},
  publisher    = {{American Diabetes Association Inc.}},
  series       = {{Diabetes}},
  title        = {{Auto- and alloimmune reactivity to human islet allografts transplanted into type 1 diabetic patients}},
  url          = {{http://dx.doi.org/10.2337/diabetes.48.3.484}},
  doi          = {{10.2337/diabetes.48.3.484}},
  volume       = {{48}},
  year         = {{1999}},
}