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

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.

Eosinophil‐to‐monocyte ratio is an excellent predictor of acute cellular rejection in pancreas transplant alone recipients

“…According to Fingerle‐Rowson et al, a glucocorticoid causes selective depletion of CD14 + CD16 + monocytes without change of the total monocyte count. Recent studies have reported that this type of monocyte has a correlation with a higher rate of acute rejection …”

“…25 We also observed that the number of this type of monocyte has a correlation with a higher rate of acute rejection. 17,[40][41][42] We do not know whether there is a direct biologic connection between eosinophils and monocytes. The elevated EMR is just an observed phenomenon.…”

Epidemiological profile of the pancrêas-rim transplant and analysis of the immunological markers of rejection

“…Estudos recentes demonstraram também que os Autoanticorpos Pancreáticos (AAb) são fatores de risco. Haja vista que piora a sobrevida do enxerto de pâncreas, sobretudo quando associado após Transplante de Pâncreas/Rim (TSPR) (Rodelo-Haad, 2019).…”