Veronica Santilli1, Alberto Cagigi2, Isabella Guzzo3, Stefano Rinaldi4, Nadia Mora2, Federica Zotta2, Antonina Piazza5, Paolo Rossi2,4, Francesco Emma3, Luca Dello Strologo3, Paolo Palma2. 1. University Department of Pediatrics, DPUO, Unit of Immune and Infectious Diseases, Bambino Gesù Children's Hospital and Research Institute (IRCCS), Piazza S. Onofrio 4, 00165, Rome, Italy. veronica.santilli@hotmail.it. 2. University Department of Pediatrics, DPUO, Unit of Immune and Infectious Diseases, Bambino Gesù Children's Hospital and Research Institute (IRCCS), Piazza S. Onofrio 4, 00165, Rome, Italy. 3. Nephrology and Urology Department, Bambino Gesù Children's Hospital and Research Institute (IRCCS), Piazza S. Onofrio 4, 00165, Rome, Italy. 4. Chair of Pediatrics, Department of Public Health, University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy. 5. National Council of Researches IFT Unit of Rome S. Camillo Hospital - Regional Transplant Center Lazio, S. Camillo Hospital, C.ne Gianicolense 87, 00152, Rome, Italy.
Abstract
BACKGROUND: In the field of kidney transplantation, identifying early signatures of humoral rejection is a key challenge. METHODS: We investigated the presence of anti-HLA antibodies and the distribution of lymphocyte subpopulations in 77 kidney-transplanted children and young adults compared to 23 healthy controls. Moreover, we tested whether the presence of anti-HLA antibodies could be related to modification in lymphocyte phenotype. Finally, we correlated the presence of anti-HLA antibodies and specific alteration of lymphocyte subsets with clinical outcomes. RESULTS: In kidney-transplanted children who developed anti-HLA antibodies, we observed an expansion of double-negative B cells (CD19 + CD27-IgD-), indicating premature aging of this compartment. Moreover, we reported signs of impaired B cell regulation, indicated by a higher IL-21R+ B cell frequency associated with an abnormal increase of follicular helper T cells. Finally, a considerable reduction in CD8+ effector T and invariant Natural killer T (NKT) cells was observed. The stability of graft function over time is significantly correlated with the frequency of peripheral effector CD4+ and CD8+ T cells and invariant NKT cells. CONCLUSIONS: This study supports the usefulness of lymphocyte subset as one of a spectrum of early diagnostic tools required to identify patients at risk of developing donor alloimmune response.
BACKGROUND: In the field of kidney transplantation, identifying early signatures of humoral rejection is a key challenge. METHODS: We investigated the presence of anti-HLA antibodies and the distribution of lymphocyte subpopulations in 77 kidney-transplanted children and young adults compared to 23 healthy controls. Moreover, we tested whether the presence of anti-HLA antibodies could be related to modification in lymphocyte phenotype. Finally, we correlated the presence of anti-HLA antibodies and specific alteration of lymphocyte subsets with clinical outcomes. RESULTS: In kidney-transplanted children who developed anti-HLA antibodies, we observed an expansion of double-negative B cells (CD19 + CD27-IgD-), indicating premature aging of this compartment. Moreover, we reported signs of impaired B cell regulation, indicated by a higher IL-21R+ B cell frequency associated with an abnormal increase of follicular helper T cells. Finally, a considerable reduction in CD8+ effector T and invariant Natural killer T (NKT) cells was observed. The stability of graft function over time is significantly correlated with the frequency of peripheral effector CD4+ and CD8+ T cells and invariant NKT cells. CONCLUSIONS: This study supports the usefulness of lymphocyte subset as one of a spectrum of early diagnostic tools required to identify patients at risk of developing donor alloimmune response.
Authors: Y Ikehara; Y Yasunami; S Kodama; T Maki; M Nakano; T Nakayama; M Taniguchi; S Ikeda Journal: J Clin Invest Date: 2000-06 Impact factor: 14.808
Authors: Manuel Pascual; Tom Theruvath; Tatsuo Kawai; Nina Tolkoff-Rubin; A Benedict Cosimi Journal: N Engl J Med Date: 2002-02-21 Impact factor: 91.245
Authors: K Bienemann; K Iouannidou; K Schoenberg; F Krux; S Reuther; O Feyen; K Bienemann; F Schuster; M Uhrberg; H-J Laws; A Borkhardt Journal: Scand J Immunol Date: 2011-10 Impact factor: 3.487
Authors: E J Kim; J Kwun; A C Gibby; J J Hong; A B Farris; N N Iwakoshi; F Villinger; A D Kirk; S J Knechtle Journal: Am J Transplant Date: 2014-01 Impact factor: 8.086
Authors: G N de Graav; M Dieterich; D A Hesselink; K Boer; M C Clahsen-van Groningen; R Kraaijeveld; N H R Litjens; R Bouamar; J Vanderlocht; M Tilanus; I Houba; A Boonstra; D L Roelen; F H J Claas; M G H Betjes; W Weimar; C C Baan Journal: Clin Exp Immunol Date: 2015-05 Impact factor: 4.330
Authors: Pablo J E J van de Berg; Eveline C Hoevenaars; Si-La Yong; Karlijn A M I van Donselaar-van der Pant; Anne van Tellingen; Sandrine Florquin; René A W van Lier; Fréderike J Bemelman; Ineke J M ten Berge Journal: Immunology Date: 2012-06 Impact factor: 7.397
Authors: F Porcheray; J W Fraser; B Gao; A McColl; J DeVito; I Dargon; Y Helou; W Wong; T C Girouard; S L Saidman; R B Colvin; A Palmisano; U Maggiore; A Vaglio; R N Smith; E Zorn Journal: Am J Transplant Date: 2013-08-06 Impact factor: 8.086