Immune monitoring and risk of infection in pediatric liver transplantation: a prospective study

Ricardo Cuesta Martín De La Cámara^1,2,3*Laura Miguel-Berenguel^1,3Carmen Cámara^1,4Itsaso Losantos⁵Esteban Frauca-Remacha^6,7,8Loreto Hierro^6,7,8Gema Muñoz-Bartolo^6,7,8María Dolores Lledín-Barbacho^6,7,8Ana Martinez Feito¹Eduardo Lopez-Granados^1,4,8,9Elena Sánchez Zapardiel^1,4,8,9

• ¹Clinical Immunology, University Hospital La Paz, La Paz, Spain
• ²PhD School, University Hospital La Paz Research Institute (IdiPAZ), Madrid, Madrid, Spain
• ³Autonomous University of Madrid, Madrid, Madrid, Spain
• ⁴University Hospital La Paz Research Institute (IdiPAZ), Madrid, Madrid, Spain
• ⁵Biostatistics Platform, University Hospital La Paz, La Paz, Spain
• ⁶Paediatric Hepatology, University Hospital La Paz, La Paz, Spain
• ⁷European Reference Network (ERN), RARE LIVER, Madrid, Asturias, Spain
• ⁸European Reference Network (ERN), TransplantChild, Madrid, Asturias, Spain
• ⁹U767, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Madrid Community, Spain

Background: Immune monitoring has been proposed to optimize immunosuppressive therapy in liver recipients. This study aims to describe immunological changes following liver transplantation in pediatric recipients and to identify immune markers associated with post-transplant complications.The immunological status of 95 pediatric liver recipients was prospectively assessed before transplantation and at 1, 3, 6, 9 and 12 months post-transplantation. Serum immunoglobulins (Ig) were measured by nephelometry and immunophenotype was evaluated by flow cytometry. T, B and NK lymphocyte counts were adjusted for age using standard reference ranges.Results: Graft rejection, post-transplant lymphoproliferative disorder and autoimmune hepatitis was diagnosed in 6%, 2% and 0% patients, respectively. Early infections affected 43% patients, while late infections occurred in 17%, 24%, 10% and 9% recipients at each follow-up interval. Baseline immune dysregulation primarily involved the cellular compartment, with 78% recipients showing lymphopenia. Lymphocyte subpopulation scores improved following liver transplantation, with CD4 + score normalizing by month 1 and CD8 + , CD19 + and NK scores by month 6. First-month IgG hypogammaglobulinemia, observed in 20% recipients, resolved completely at month 12. First-month T-cell lymphopenia (CD3 + hazard ratio [HR] 2.48, p=0.005; CD8 + HR 2.38, p=0.008) and hypogammaglobulinemia (IgG HR 2.18, p=0.036; IgA HR 2.40, p=0.011; IgM HR 2.61, p=0.006) were associated with higher risk of late infections. In multivariate analysis, only CD3 + T-cell lymphopenia remained a significant predictor (HR 2.13, p=0.030).Conclusions: Baseline immune dysregulation resolved within the first months posttransplantation. Early infections were unrelated to immune markers, while late infections were associated with CD3 + T-cell lymphopenia and hypogammaglobulinemia.