IL‐10‐specific autoantibodies predict major adverse cardiovascular events in kidney transplanted patients ‐ a retrospective cohort study

Abstract

End-stage renal failure is associated with persistent systemic inflammation. The aim of this study was to investigate if systemic inflammation at the time of kidney transplantation is linked to poor graft survival, major adverse cardiovascular events (MACE), and increased mortality, and if these processes are modulated by naturally occurring cytokine-specific autoantibodies (c-aAbs), which have been shown to regulate cytokine activity in vitro. Serum levels of cytokines, high-sensitivity C-reactive protein (hsCRP) and c-aAbs specific for interleukin (IL)-1a, tumor necrosis factor (TNF)-a, IL-6, and IL-10 were measured at the time of transplantation in a retrospective cohort study of 619 kidney transplanted patients with a median follow-up of 4.9 years (range 1.2-8.2 years). Systemic inflammation was associated with all-cause mortality in simple and multiple Cox regression analyses. IL-10-specific c-aAbs were associated with MACE after transplantation, suggesting that IL-10 may be a protective factor. Similarly, patients with a history of MACE before transplantation had lower levels of TNF-a-specific c-aAbs, hence we hypothesized that TNF may be a risk factor of MACE. These findings support that pro-inflammatory activity before transplantation is a pathological driver of MACE and all-cause mortality after transplantation. This information adds to pretransplantation risk estimation in renal transplant candidates. Transplant International 2019; 32: 933-948

Cytokine Autoantibodies Are Associated with Infection Risk and Self-Perceived Health: Results from the Danish Blood Donor Study

“…Notably, we observed the same pattern for self-reported health scores as we did for antibacterial prescriptions, so women with a high level of IL-10 c-aAb had increased odds of high (good) PCS scores, again suggesting a potentially protective and positive effect of IL-10 c-aAb. It should be emphasized that the effects of IL-10 c-aAb are likely highly context-specific, as another previous study from our research group reported that IL-10 c-aAb were associated with increased risk of major adverse cardiovascular events (MACE) in kidney-transplanted patients, an outcome that is intrinsically linked to a pro-inflammatory environment [33]. Thus, though protective in regard to infections in healthy individuals, IL-10 c-aAb may constitute a risk factor for patients in whom excess inflammation may tip a balance towards adverse events such as organ transplant patients and autoimmune disease in general, again due to the cytokines' many immunoregulatory functions [34,35].…”

Cytokine autoantibodies are stable throughout the haematopoietic stem cell transplantation course and are associated with distinct biomarker and blood cell profiles

“…Cytokines are key factors in this condition; several proinflammatory cytokines, including IL-4, IL-6 and IL-17, serve as markers of chronic GvHD, and many current treatments for GvHD involve targeting cytokines 31 . Based on their immunomodulatory potential and a prior study of kidney-transplanted patients, which found that high-titre IL-10 c-aAbs were associated with increased odds of cardiac disease 32 , we therefore hypothesized that high-titre c-aAbs may influence clinical HSCT outcomes. We however found no evidence for this.…”

IL-6 Autoantibodies Predict Lower Platelet Counts and Altered Plasma Cytokine Profiles in Healthy Blood Donors: Results From the Danish Blood Donor Study

“…IL-6 c-aAb have been associated with bacterial infections and concurrent low CRP in several case studies (22)(23)(24). In hemostasis, c-aAb against IL-10, an IL-6 suppressor, are associated with an increased risk of major adverse cardiovascular events in kidney transplanted patients (25). Furthermore, treatment with antibodies directed against IL-6 [tocilizumab R (Actemra)] is associated with reductions in platelet counts (26).…”