High frequency of central memory regulatory T cells allows detection of liver recipients at risk of early acute rejection within the first month after transplantation.
Several studies have analyzed the potential of T regulatory cells (Treg cells) as biomarkers of acute rejection (AR). The aim of the present multicenter study was to correlate the percentage of peripheral Treg cells in liver graft recipients drawn at baseline up to 12 months after transplantation with the presence of AR. The percentage of central memory (cm) Treg cells (CD4(+)CD25(high)CD45RO(+)CD62L(+)) was monitored at pre-transplant and at 1 and 2 weeks, and 1, 2, 3 and 6 months and 1 year post-transplantation. The same validation standard operating procedures were used in all participating centers. Fifteen patients developed AR (23.4%). Hepatitis C virus recurrence was observed in 16 recipients, who displayed low peripheral blood cmTreg levels compared with patients who did not. A steady increase of cmTregs was observed during the first month after transplantation with statistically significant differences between AR and non-AR patients. The high frequency of memory Treg cells allowed us to monitor rejection episodes during the first month post-transplantation. On the basis of these data, we developed a prediction model for assessing risk of AR that can provide clinicians with useful information for managing patients individually and customizing immunosuppressive therapies.
Servicio de Inmunología, Hospital Clínico Universitario Virgen de la Arrixaca, IMIB, Murcia, Spain.
Francisco
F
Boix-Giner
Farmacología y Toxicología, Centro de Diagnóstico Biomédico, IDIBAPS, Hospital Clínico, Universidad de Barcelona, Barcelona, Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.
Olga
O
Millan
Servicio de Inmunología, Hospital Universitario Marqués de Valdecilla-IDIVAL, Santander, Spain.
David
D
San Segundo
Servicio de Epidemiologia, Gerencia de Atención Primaria-IFIMAV, Santander, Spain.
Pedro
P
Muñoz-Cacho
Servicio de Inmunología, Hospital Universitario 12 de Octubre, Madrid, Spain.
Esther
E
Mancebo
Servicio de Nefrologia, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain.
Santiago
S
Llorente
Unidad de Hígado, Hospital Clínico, IDIBAPS, Barcelona, Spain.
Lourdes
L
Rafael-Valdivia
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain Unidad de Hígado, Hospital Clínico, IDIBAPS, Barcelona, Spain.
Antoni
A
Rimola
Servicio de Aparato Digestivo, Hospital Universitario Marqués de Valdecilla-IDIVAL, Santander, Spain.
Emilio
E
Fábrega
Servicio de Inmunología, Hospital Clínico Universitario Virgen de la Arrixaca, IMIB, Murcia, Spain.
Anna
A
Mrowiec
Servicio de Inmunología, Hospital Universitario 12 de Octubre, Madrid, Spain.
Luis
L
Allende
Servicio de Inmunología, Hospital Clínico Universitario Virgen de la Arrixaca, IMIB, Murcia, Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.
Alfredo
A
Minguela
Servicio de Inmunología, Hospital Clínico Universitario Virgen de la Arrixaca, IMIB, Murcia, Spain.
Jose M
JM
Bolarín
Servicio de Inmunología, Hospital Universitario 12 de Octubre, Madrid, Spain.
Estela
E
Paz-Artal
Servicio de Inmunología, Hospital Universitario Marqués de Valdecilla-IDIVAL, Santander, Spain.
Marcos
M
López-Hoyos
Farmacología y Toxicología, Centro de Diagnóstico Biomédico, IDIBAPS, Hospital Clínico, Universidad de Barcelona, Barcelona, Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.
Mercé
M
Brunet
Servicio de Inmunología, Hospital Clínico Universitario Virgen de la Arrixaca, IMIB, Murcia, Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain manuel.muro@carm.es manuel.muro@um.es.
Manuel
M
Muro
D000208:Acute Disease; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000175:diagnosis* / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*; D055815:Young Adult
D015703:Antigens, CD; D015415:Biomarkers
Treg; acute rejection; liver transplantation; receiver operating characteristic curves