Allospecific CD154+ T cells identify rejection-prone recipients after pediatric small-bowel transplantation

Ashokkumar, Chethan; Gupta, Ankit; Sun, Qing; Ningappa, Mylarappa; Higgs, Brandon W.; Mazariegos, George; Fazzolare, Tamara; Remaley, Lisa; Soltys, Kyle; Bond, Geoffrey; Abu‐Elmagd, Kareem; Sindhi, Rakesh

doi:10.1016/j.surg.2009.04.006

Cited by 38 publications

(40 citation statements)

References 18 publications

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“…Allospecific CD154 ϩ TcM measure donor-specific alloreactivity, which is uniformly enhanced with allograft rejection. 5,38 Our previous studies also demonstrate that the rejection threshold of CD154 ϩ TcM, if present before ITx, has a sensitivity of 100% and specificity of 90% for prediction of early ITx rejection. 6 In the present study, significant correlations are seen between this cell type and peripheral blood CCL5 gene expression before (P ϭ 0.004) and after ITx (P ϭ 0.042).…”

Section: Discussionmentioning

confidence: 84%

“…Expressed as the immunoreactivity index IR or the ratio of donor-to third-party-induced CD154 ϩ TcM, the cell type has a sensitivity of 93% and specificity 88% for association with ITx rejection if the IR is Ն1.23. 5 Peripheral blood corresponding to biopsies in the validation cohort was consumed in other studies. Therefore, peripheral blood candidate genes were also replicated in blood samples obtained during a quiescent rejection-free period late after ITx in an additional test cohort of nine recipients (four rejectors, five nonrejectors).…”

Section: Methodsmentioning

confidence: 99%

“…Donor-specific alloreactivity was measured in flow cytometric mixed-lymphocyte reaction assays, as described previously. 5 Flow cytometry antibodies were CCL5-phycoerythrin, CD14-allophycocyanin-Cy7, CD4-phycoerythrin-Cy5, CD8-phycoerythrin-Cy7, CD56/CD16-fluorescein isothiocyanate, CD154-phycoerythrin (BD Biosciences, San Jose, CA), and CD19-Texas Red (Beckman Coulter, Miami, FL). CD45RO-Texas Red was obtained from BeckmanCoulter.…”

Section: Flow Cytometrymentioning

confidence: 99%

“…4 Second, enhanced donor-specific alloreactivity measured by allospecific CD154 ϩ T-cytotoxic cells (TcM) can be detected before ITx and for several weeks before and after biopsy-proven rejection. 5,6 CD154 ϩ TcM are highly sensitive and specific for biopsy-proven rejection. Third, a relative excess of myeloid dendritic cells, which may have inflammatory functions, can be seen before and after rejection of cadaveric intestine allografts.…”

mentioning

confidence: 99%

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Increased Expression of Peripheral Blood Leukocyte Genes Implicate CD14+ Tissue Macrophages in Cellular Intestine Allograft Rejection

Ashokkumar

Ningappa

Ranganathan

et al. 2011

The American Journal of Pathology

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Recurrent rejection shortens graft survival after intestinal transplantation (ITx) in children, most of whom also experience early acute cellular rejection (rejectors). To elucidate mechanisms common to early and recurrent rejection, we used a test cohort of 20 recipients to test the hypothesis that candidate peripheral blood leukocyte genes that trigger rejection episodes would be evident late after ITx during quiescent periods in genome-wide gene expression analysis and would achieve quantitative real-time PCR replication pre-ITx (another quiescent period) and in the early post-ITx period during first rejection episodes. Eight genes were significantly up-regulated among rejectors in the late post-ITx and pre-ITx periods, compared with nonrejectors: TBX21, CCL5, GNLY, SLAMF7, TGFBR3, NKG7, SYNE1, and GK5. Only

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Section: Discussionmentioning

confidence: 84%

Section: Methodsmentioning

confidence: 99%

Section: Flow Cytometrymentioning

confidence: 99%

mentioning

confidence: 99%

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Increased Expression of Peripheral Blood Leukocyte Genes Implicate CD14+ Tissue Macrophages in Cellular Intestine Allograft Rejection

Ashokkumar

Ningappa

Ranganathan

et al. 2011

The American Journal of Pathology

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“…Unfortunately, rapid turnaround of results is not available for either of these innovative markers and at this time routine monitoring has not been established (61). Ashokkumar et al (62) reported an alternative marker with >90% sensitivity and specificity for acute intestine allograft rejection. This apparently highly reliable marker utilizes an assessment of donor-induced response of recipient cytotoxic T memory cells in a mixed lymphocyte reaction (62).…”

Section: Biomarkers For Allograft Monitoringmentioning

confidence: 99%

The Current State of Intestine Transplantation: Indications, Techniques, Outcomes and Challenges

Sudan

2014

American Journal of Transplantation

112

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Intestine transplantation is the least common form of organ transplantation in the United States and often deemed one of the most difficult. Patient and graft survival have historically trailed well behind other organ transplants. Over the past 5-10 years registry reports and single center series have demonstrated improvements to patient survival after intestinal transplantation that now match patient survival for those without life-threatening complications on parenteral nutrition. For various reasons including improvements in medical care of patients with intestinal failure and difficulty accessing transplant care, the actual number of intestine transplants has declined by 25% over the past 6 years. In light of the small numbers of intestine transplants, many physicians and the lay public are often unaware that this is a therapeutic option. The aim of this review is to describe the current indications, outcomes and advances in the field of intestine transplantation and to explore concerns over future access to this important and life-saving therapy.

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GI and Liver Transplantation Pathology in Childhood

Ranganathan

2024

Pathology of Pediatric Gastrointestinal and Liver Disease

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Allospecific CD154+ T cells identify rejection-prone recipients after pediatric small-bowel transplantation

Cited by 38 publications

References 18 publications

Increased Expression of Peripheral Blood Leukocyte Genes Implicate CD14+ Tissue Macrophages in Cellular Intestine Allograft Rejection

Increased Expression of Peripheral Blood Leukocyte Genes Implicate CD14+ Tissue Macrophages in Cellular Intestine Allograft Rejection

The Current State of Intestine Transplantation: Indications, Techniques, Outcomes and Challenges

GI and Liver Transplantation Pathology in Childhood

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