BACKGROUND: As a significant determinant of T- and B-cell cooperation, CD154 has been used to identify allospecific T-cytotoxic memory cells (TcM) for rejection risk assessment with high sensitivity or specificity but not for alloreactive B-cells, especially among recipients predisposed to acute cellular and humoral rejection, that is, children with intestinal transplantation (ITx). METHODS: Single blood samples from 32 pediatric ITx after lymphocyte depleting induction therapy were obtained within 30 days of protocol biopsies. Samples were assayed for allospecific CD154CD19 B cells and allospecific CD154 TcM in 16-hr live-cell mixed leukocyte reaction using multiparametric flow cytometry. Results were expressed as the immunoreactivity index (IR) or the ratio of donor- to third-party-induced CD154 B cells or TcM. The rejection threshold IR of B cells was determined by logistic regression, leave-one-out cross-validation, and receiver operating characteristic analyses. RESULTS: Biopsy-proven acute cellular rejection was present in 15 subjects (rejectors) and absent in 17 (nonrejectors). In archived serum samples from 16 of 32 subjects donor-specific anti-HLA antibodies (DSA) were assayed by Luminex bead array. DSA were absent in all 7 nonrejectors but present in 7 of 9 rejectors. The IR of allospecific CD154CD19 B cells more than or equal to 1.351 was associated with rejector status and was present in 13 of 15 rejectors (sensitivity 87%) and absent in 15 of 17 nonrejectors (specificity 88%). Excellent correlations were seen between CD154CD19 B cells and CD154 TcM (Spearman ρ=0.647, P=0.0001) but could not be tested independently for DSA, which was highly correlated with rejector status and with CD154 TcM. CONCLUSIONS: Allospecific CD154CD19 B cells identify rejection-prone children with ITx and can likely substitute for T-cell alloreactivity in estimating rejection risk in this rare subject population.
BACKGROUND: As a significant determinant of T- and B-cell cooperation, CD154 has been used to identify allospecific T-cytotoxic memory cells (TcM) for rejection risk assessment with high sensitivity or specificity but not for alloreactive B-cells, especially among recipients predisposed to acute cellular and humoral rejection, that is, children with intestinal transplantation (ITx). METHODS: Single blood samples from 32 pediatric ITx after lymphocyte depleting induction therapy were obtained within 30 days of protocol biopsies. Samples were assayed for allospecific CD154CD19 B cells and allospecific CD154 TcM in 16-hr live-cell mixed leukocyte reaction using multiparametric flow cytometry. Results were expressed as the immunoreactivity index (IR) or the ratio of donor- to third-party-induced CD154 B cells or TcM. The rejection threshold IR of B cells was determined by logistic regression, leave-one-out cross-validation, and receiver operating characteristic analyses. RESULTS: Biopsy-proven acute cellular rejection was present in 15 subjects (rejectors) and absent in 17 (nonrejectors). In archived serum samples from 16 of 32 subjects donor-specific anti-HLA antibodies (DSA) were assayed by Luminex bead array. DSA were absent in all 7 nonrejectors but present in 7 of 9 rejectors. The IR of allospecific CD154CD19 B cells more than or equal to 1.351 was associated with rejector status and was present in 13 of 15 rejectors (sensitivity 87%) and absent in 15 of 17 nonrejectors (specificity 88%). Excellent correlations were seen between CD154CD19 B cells and CD154 TcM (Spearman ρ=0.647, P=0.0001) but could not be tested independently for DSA, which was highly correlated with rejector status and with CD154 TcM. CONCLUSIONS: Allospecific CD154CD19 B cells identify rejection-prone children with ITx and can likely substitute for T-cell alloreactivity in estimating rejection risk in this rare subject population.
Authors: Udeme D Ekong; Xunrong Luo; Min Yu; Delli Wang; Stephen D Miller; Maurice R G O'Gorman Journal: Hum Immunol Date: 2011-02-26 Impact factor: 2.850
Authors: Kyle A Soltys; Kentaro Setoyama; Edgar N Tafaleng; Alejandro Soto Gutiérrez; Jason Fong; Ken Fukumitsu; Taichiro Nishikawa; Masaki Nagaya; Rachel Sada; Kimberly Haberman; Roberto Gramignoli; Kenneth Dorko; Veysel Tahan; Alexandra Dreyzin; Kevin Baskin; John J Crowley; Mubina A Quader; Melvin Deutsch; Chethan Ashokkumar; Benjamin L Shneider; Robert H Squires; Sarangarajan Ranganathan; Miguel Reyes-Mugica; Steven F Dobrowolski; George Mazariegos; Rajavel Elango; Donna B Stolz; Stephen C Strom; Gerard Vockley; Jayanta Roy-Chowdhury; Marilia Cascalho; Chandan Guha; Rakesh Sindhi; Jeffrey L Platt; Ira J Fox Journal: J Hepatol Date: 2016-12-24 Impact factor: 25.083
Authors: James E Squires; Kyle A Soltys; Patrick McKiernan; Robert H Squires; Stephen C Strom; Ira J Fox; Alejandro Soto-Gutierrez Journal: Curr Transplant Rep Date: 2017-10-14