Immune "tolerance profiles" in donor bone marrow infused kidney transplant patients using multiple ex vivo functional assays

James M. Mathew, Gaetano Ciancio, George W Burke, Rolando O. Garcia-Morales, Anne Rosen, Edward Wang, Carmen I. Gomez, Bonnie B Blomberg, Laphalle Fuller, Violet Esquenazi, Camillo Ricordi, Joshua Miller

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Ex vivo identification of donor-specific unresponsiveness in organ transplant recipients is important for immunosuppression (IS) minimization. We tested three groups of stable living, related-donor kidney transplant patients up to 11 years postoperatively, i.e., 20 haploidenticals with donor bone marrow cell (DBMC) infusions, eight noninfused haploidentical controls (haplo controls), and 11 HLA-identical controls (HLA-id), using multiple ex vivo immune assays. We observed that no patients developed donor-specific antibodies. The majority showed donor-specific CTL unresponsiveness from year 1 onward. Thirteen of 20 DBMC recipients became specifically donor MLR nonreactive. Depletion of donor cells in DBMC recipients still MLR reactive increased donor-specific reactivity by 75% 36% (p = 0.04). Adding them back in low concentration caused antigen specific inhibition. The frequencies of ELISPOT granzyme-B and interferon-γ-producing cells somewhat paralleled the CTL and MLR responses. In the trans vivo DTH, 14 of 19 DBMC recipients demonstrated donor-specific unresponsiveness and 16 of 19 showed "linked suppression," vs none of eight and one of eight haplo controls and vs six of 10 and one of 10 HLA-ids, respectively. Most importantly, when all six assays were performed simultaneously, 10 of 18 DBMC, five of 10 HLA-ids, and no haplo controls were specifically donor unresponsive long term. We propose that a cluster analysis combining these assays will reveal tolerant recipients in whom IS minimization may safely be tested. This appears to have occurred in many DBMC-infused recipients.

Original languageEnglish
Pages (from-to)566-576
Number of pages11
JournalHuman Immunology
Volume71
Issue number6
DOIs
StatePublished - Jun 1 2010

Fingerprint

Immune Tolerance
Bone Marrow
Tissue Donors
Transplants
Kidney
Bone Marrow Cells
Immunosuppression
Enzyme-Linked Immunospot Assay
Granzymes
Living Donors
Interferons
Cluster Analysis

Keywords

  • Donor bone marrow infusion
  • Donor-specific unresponsiveness
  • Immune assessments
  • Kidney transplant patients

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Immune "tolerance profiles" in donor bone marrow infused kidney transplant patients using multiple ex vivo functional assays. / Mathew, James M.; Ciancio, Gaetano; Burke, George W; Garcia-Morales, Rolando O.; Rosen, Anne; Wang, Edward; Gomez, Carmen I.; Blomberg, Bonnie B; Fuller, Laphalle; Esquenazi, Violet; Ricordi, Camillo; Miller, Joshua.

In: Human Immunology, Vol. 71, No. 6, 01.06.2010, p. 566-576.

Research output: Contribution to journalArticle

Mathew, James M. ; Ciancio, Gaetano ; Burke, George W ; Garcia-Morales, Rolando O. ; Rosen, Anne ; Wang, Edward ; Gomez, Carmen I. ; Blomberg, Bonnie B ; Fuller, Laphalle ; Esquenazi, Violet ; Ricordi, Camillo ; Miller, Joshua. / Immune "tolerance profiles" in donor bone marrow infused kidney transplant patients using multiple ex vivo functional assays. In: Human Immunology. 2010 ; Vol. 71, No. 6. pp. 566-576.
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AU - Ciancio, Gaetano

AU - Burke, George W

AU - Garcia-Morales, Rolando O.

AU - Rosen, Anne

AU - Wang, Edward

AU - Gomez, Carmen I.

AU - Blomberg, Bonnie B

AU - Fuller, Laphalle

AU - Esquenazi, Violet

AU - Ricordi, Camillo

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AB - Ex vivo identification of donor-specific unresponsiveness in organ transplant recipients is important for immunosuppression (IS) minimization. We tested three groups of stable living, related-donor kidney transplant patients up to 11 years postoperatively, i.e., 20 haploidenticals with donor bone marrow cell (DBMC) infusions, eight noninfused haploidentical controls (haplo controls), and 11 HLA-identical controls (HLA-id), using multiple ex vivo immune assays. We observed that no patients developed donor-specific antibodies. The majority showed donor-specific CTL unresponsiveness from year 1 onward. Thirteen of 20 DBMC recipients became specifically donor MLR nonreactive. Depletion of donor cells in DBMC recipients still MLR reactive increased donor-specific reactivity by 75% 36% (p = 0.04). Adding them back in low concentration caused antigen specific inhibition. The frequencies of ELISPOT granzyme-B and interferon-γ-producing cells somewhat paralleled the CTL and MLR responses. In the trans vivo DTH, 14 of 19 DBMC recipients demonstrated donor-specific unresponsiveness and 16 of 19 showed "linked suppression," vs none of eight and one of eight haplo controls and vs six of 10 and one of 10 HLA-ids, respectively. Most importantly, when all six assays were performed simultaneously, 10 of 18 DBMC, five of 10 HLA-ids, and no haplo controls were specifically donor unresponsive long term. We propose that a cluster analysis combining these assays will reveal tolerant recipients in whom IS minimization may safely be tested. This appears to have occurred in many DBMC-infused recipients.

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