Rodelo-Haad, CristianAgüera, Maria LuisaCarmona, AndresNavarro, Maria DoloresCarracedo, JuliaRodriguez-Benot, AlbertoAljama, Pedro2023-01-252023-01-252019-02-05Rodelo-Haad C, Agüera ML, Carmona A, Navarro MD, Carracedo J, Rodriguez-Benot A, et al. Pancreatic autoantibodies and CD14+CD16+ monocytes subset are associated with the impairment of ß-cell function after simultaneous pancreas-kidney transplantation. PLoS One. 2019 Feb 22;14(2):e0212547http://hdl.handle.net/10668/13610Pancreatic 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 (pp<0.001) and lower C-pep levels (p<0.001) compared to those who remained AAb- throughout the follow-up. In the crosssectional 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 proinflammatory 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 othergroups (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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/AdultAutoantibodiesAutoantigensB-lymphocytesCross-sectional studiesFemaleHumansKidney transplantationLeukocyte countLongitudinal studiesMaleMonocytesPancreasPancreas transplantationresearch article30794611open accessEstudios longitudinalesMonocitosRecuento de leucocitosTrasplante de páncreasTrasplante de riñón10.1371/journal.pone.02125471932-6203PMC6386378https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0212547&type=printablehttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386378/pdf