title: Soluble co-signaling molecules predict long-term graft outcome in kidney-transplanted patients.
abstract: Co-signaling molecules are responsible for full T-cell activation after solid organ transplantation. Their increased expression can lead to the release of a soluble form that can modulate the immune response post-transplantation. We analyzed the presence of co-signaling molecules (sCD30, sCD40, sCD137, sCTLA-4, sCD80, sCD28, sCD40L, sPD-1, and sPD-L1) in serum from kidney-transplanted patients (n = 59) obtained at different times (before transplantation, and 15 days, 3 months and 1 year post-transplantation) and their contribution to graft outcome was evaluated using principal component analysis. Before transplantation, high levels of soluble co-signaling molecules (mainly sCD30, sCD137 and sCD40) were detected in all patients. These molecules were modulated soon after receiving an allograft but never attained similar levels to those of healthy controls. A signature based on the determination of six soluble co-stimulatory (sCD30, sCD40, sCD137 and sCD40L) and co-inhibitory (sPD-1 and sPD-L1) molecules at 3 months post-transplantation allowed a group of patients to be identified (27.12%) with a worse long-term graft outcome. Patients with high levels of soluble molecules showed a progressive and gradual deterioration of kidney function (increased creatinine and proteinuria levels and decreased estimated glomerular filtration rate) over time and a higher risk of graft loss at 6 years post-transplantation than patients with low levels of these molecules (62.55% versus 5.14%, p<0.001). Thus, our data show an aberrant expression of soluble co-signaling molecules in kidney-transplanted patients whose quantification at 3 months post-transplantation might be a useful biomarker of immune status and help to predict long-term graft evolution.
authors.affiliation: Department of Nephrology, Hospital Universitario Central de Asturias, Oviedo, Spain; Department of Nephrology, Hospital Son Llátzer, Palma de Mallorca, Spain.
authors.forename: Susana G
authors.initials: SG
authors.lastname: Melendreras
authors.affiliation: Oficina de Investigación Biosanitaria de Asturias (OIB-FICYT), Oviedo, Spain; Universidad Autónoma de Chile, Santiago de Chile, Chile.
authors.forename: Pablo
authors.initials: P
authors.lastname: Martínez-Camblor
authors.affiliation: Department of Immunology, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Aurora
authors.initials: A
authors.lastname: Menéndez
authors.affiliation: Department of Immunology, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Bravo-Mendoza
authors.affiliation: Oficina de Investigación Biosanitaria de Asturias (OIB-FICYT), Oviedo, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: González-Vidal
authors.affiliation: Genética Molecular-Laboratorio de Medicina, Hospital Universitario Central de Asturias, Oviedo, Spain; Fundación Renal Iñigo Álvarez de Toledo, Madrid, Spain.
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
authors.affiliation: Department of Nephrology, Hospital Universitario Central de Asturias, Oviedo, Spain; Fundación Renal Iñigo Álvarez de Toledo, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Díaz-Corte
authors.affiliation: Cellular Biology of Renal Diseases Laboratory, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Universidad Autónoma Madrid, Madrid, Spain; Fundación Renal Iñigo Álvarez de Toledo, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Ruiz-Ortega
authors.affiliation: Department of Immunology, Hospital Universitario Central de Asturias, Oviedo, Spain; Fundación Renal Iñigo Álvarez de Toledo, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: López-Larrea
authors.affiliation: Cellular Biology of Renal Diseases Laboratory, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Universidad Autónoma Madrid, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Suárez-Álvarez
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000097:blood* / Q000276:immunology / Q000473:pathology; D006085:Graft Survival / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007668:Kidney / Q000276:immunology / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014184:Transplantation, Homologous
chemical_list: D015703:Antigens, CD; D015415:Biomarkers