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Pancreatic autoantibodies and CD14+CD16+ monocytes subset are associated with the impairment of ß-cell function after simultaneous pancreas-kidney transplantation

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Rodelo-Haad, Cristian and Agüera, María Luisa and Carmona, Andrés and Navarro, María Dolores and Carracedo, Julia and Rodríguez-Benot, Alberto and Aljama, Pedro (2019) Pancreatic autoantibodies and CD14+CD16+ monocytes subset are associated with the impairment of ß-cell function after simultaneous pancreas-kidney transplantation. PloS ONE, 14 (2). pp. 1-16. ISSN 1932-6203

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Official URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0212547



Abstract

Pancreatic autoantibodies (AAb) has been associated with a worse pancreas graft survival after simultaneous pancreas-kidney transplantation (SPK). However, due to the variable time for AAb to become positive and the lack of early biomarkers suggesting such autoimmune activation, the mechanisms leading ß-cell destruction remain uncertain. The present study aimed to evaluate the association between post-transplant AAb and the functional impairment of the pancreatic ß-cell and also the association of such AAb with inflammation after SPK. In a longitudinal study, we analyzed the impact of post-transplant glutamic acid decarboxylase (GAD-65) and the insulinoma-associated autoantigen 2 (IA-2) AAb on pancreas graft function. Serum Hb1Ac and C-peptide (C-pep) were longitudinally compared between a group with positive posttransplant AAb (AAb+; n = 40) and another matched group with negative AAb (AAb-; n = 40) until the fifth year following seroconversion. In the cross-sectional analysis, we further evaluated the systemic signatures of inflammation by measuring pro-inflammatory CD14+CD16+ monocytes by flow-cytometry and interleukin 17-A serum levels in 38 SPK recipients and ten healthy controls. In the longitudinal study, patients with AAb+ showed higher levels of Hb1Ac (p<0.001) and lower C-pep levels (p<0.001) compared to those who remained AAb- throughout the follow-up. In the cross-sectional study, AAb+ patients showed a higher percentage of CD14+CD16+ monocytes compared with those with AAb- and the healthy controls (6.70±4.19% versus 4.0±1.84% and 3.44±0.93%; p = 0.026 and 0.009 respectively). Also, CD14+CD16+ monocytes correlated with Hb1Ac and C-pep serum levels. Multivariate logistic regression showed that posttransplant AAb+ was independently associated with a higher percentage of pro-inflammatory monocytes (adjusted-OR 1.59, 95%CI 1.05–2.40, p = 0.027). The group of patients with positive AAb also showed higher levels of IL17A as compared with the other groups (either healthy control or the negative AAb subjects). In conclusion, pancreatic AAb+ after SPK were not only associated with higher Hb1Ac and lower c-peptide serum levels but also with an increased percentage of CD14+CD16+ monocytes and higher levels of circulating IL17-A.

Resumen (otros idiomas)

En los pacientes con enfermedad renal terminal (ERT) secundaria a Diabetes tipo 1 (T1D), el trasplante simultáneo de páncreas y riñón (SPK) se ha convertido en la mejor opción para restaurar el control de la glucosa y la función renal. Después del SPK, y a pesar de la terapia inmunosupresora, la aparición de autoanticuerpos pancreáticos (AAb) se han asociado con una peor supervivencia del injerto de páncreas. Sin embargo, todavía no se conocen los mecanismos implicados en este proceso. El objetivo del presente estudio fue evaluar la asociación entre AAb postrasplante y el deterioro funcional de la célula ß pancreática, así como la asociación de los AAb con la inflamación después del SPK. En un estudio que incluyó 38 receptores SPK y diez controles sanos, analizamos señales de inflamación caracterizando los monocitos pro-inflamatorios CD14+CD16+ por citometría de flujo y los niveles séricos de interleucina 17-A. Un análisis de regresión logística multivariada mostró que el nivel de AAb+ postrasplante se asoció de forma independiente con un mayor porcentaje de monocitos proinflamatorios y con niveles más altos de IL17A. Con los resultados obtenidos, se plantea la hipótesis de que uno de los posibles mecanismos a través de los cuales se promueve el incremento de AAb+ postrasplante SPK es la inducción de la microinflamación.

Item Type:Article
Subjects:Medical sciences > Medicine > Gastroenterology and Hepatology
Medical sciences > Biology > Microbiology
ID Code:57162
Deposited On:30 Sep 2019 16:23
Last Modified:30 Sep 2019 16:25

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