title: Cellular immune profile of kidney transplant patients developing anti-HLA antibodies during childhood.
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.
authors.affiliation: 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.
authors.forename: Veronica
authors.initials: V
authors.lastname: Santilli
authors.affiliation: 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.
authors.forename: Alberto
authors.initials: A
authors.lastname: Cagigi
authors.affiliation: Nephrology and Urology Department, Bambino Gesù Children's Hospital and Research Institute (IRCCS), Piazza S. Onofrio 4, 00165, Rome, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Guzzo
authors.affiliation: Chair of Pediatrics, Department of Public Health, University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Rinaldi
authors.affiliation: 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.
authors.forename: Nadia
authors.initials: N
authors.lastname: Mora
authors.affiliation: 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.
authors.forename: Federica
authors.initials: F
authors.lastname: Zotta
authors.affiliation: 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.
authors.forename: Antonina
authors.initials: A
authors.lastname: Piazza
authors.affiliation: 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.|Chair of Pediatrics, Department of Public Health, University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Rossi
authors.affiliation: Nephrology and Urology Department, Bambino Gesù Children's Hospital and Research Institute (IRCCS), Piazza S. Onofrio 4, 00165, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Emma
authors.affiliation: Nephrology and Urology Department, Bambino Gesù Children's Hospital and Research Institute (IRCCS), Piazza S. Onofrio 4, 00165, Rome, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Dello Strologo
authors.affiliation: 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.
authors.forename: Paolo
authors.initials: P
authors.lastname: Palma
mesh_terms: D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D016030:Kidney Transplantation / Q000009:adverse effects*; D016131:Lymphocyte Subsets / Q000276:immunology*; D008297:Male; D055611:Natural Killer T-Cells / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D055815:Young Adult
chemical_list: D000961:Antilymphocyte Serum; D006680:HLA Antigens
keywords: Humoral allograft rejection; Kidney transplantation; Lymphocyte subpopulations; Predictive biomarkers