Donor-Specific Anti-HLA Antibodies in Organ Transplantation: Transition from Serum DSA to Intra-Graft DSA

In the field of organ transplantation, donor-specific anti-HLA antibodies (DSA) have gained more popularity, as antibody-mediated rejection (AMR) has been recognized as an important factor to determine allograft survival. Thus, it is reasonable to believe that appropriate control of DSA is directly linked to well-managed immunosuppression, resulting in free from AMR. First, in order to prevent and manage AMR, it is of vital importance to be familiar with updated knowledge regarding crossmatch test and DSA detection methods, including intra-graft DSA. Second, it is also crucial to understand the standard criteria to diagnose AMR. Although pathological diagnosis and serum DSA (s-DSA) detection play the central role, the recent trend seems to be detection of intra-graft DSA (g-DSA). Third, regarding organ transplantation between sensitized pairs, the acceptable outcomes are obtained owing to recent preoperative desensitization protocols: depletion/modification of B cells, apheresis for antibodies, and inhibition of reaction between DSA and HLA. Finally, we would like to discuss the treatment of AMR. Further advances in diagnosis methods and emergences of effective treatments would be expected for acceptable control of AMR. In this chapter, we will review from the basics to recent topics in order to understand DSA and AMR

Myeloid-Derived Suppressor Cells as a Regulator of Immunity in Organ Transplantation

Regulation of allo-immune responses is proposed as a topic for investigation in the current field of organ transplantation. As a regulator, regulatory T cells (Tregs) have received attention due to their ability to control allograft rejection. Concurrently, however, the independent action of Tregs is not enough to achieve tolerance status in many situations. Meanwhile, as a multi-functional regulator, myeloid-derived suppressor cells (MDSCs) can suppress effector T cells as well as induce Tregs or regulatory B cells (Bregs) in certain circumstances. Furthermore, the importance of a crosstalk between MDSCs and natural killer T cells to induce tolerance has been reported. Thus, orchestration between MDSCs, myeloid regulators, T/Bregs and other lymphoid/myeloid regulators can shed light on achieving allogeneic tolerance. Here, we review the current knowledge in terms of immunological regulatory function displayed by MDSCs in the context of organ transplantation. Ideal control of MDSCs would lead to a reduction of allograft rejection and subsequent long-term allograft acceptance

Impact of Isolated High Home Systolic Blood Pressure and Diabetic Nephropathy in Patients with Type 2 Diabetes Mellitus : A 5-Year Prospective Cohort Study

Background: A previous 2-year cohort study has shown that isolated high home systolic blood pressure (IH-HSBP) may increase the risk of diabetic nephropathy, using normal HBP as a reference. However, this association has not been previously assessed in the medium to long term. Methods: This prospective 5-year cohort study of 424 patients, with normal or mildly increased albuminuria, investigated the effect of IH-HSBP on the risk of diabetic nephropathy in patients with type 2 diabetes mellitus. Diabetic nephropathy was defined as an advancement from normal or mildly increased albuminuira to moderate or severely increased albuminuria. Results: Among 424 patients, 75 developed diabetic nephropathy during the study period. The adjusted odds ratio for developing diabetic nephropathy given IH-HSBP was 2.39 (95% confidence interval, 1.15-4.96, p = 0.02). The odds ratio for developing nephropathy in patients with IH-HSBP younger than 65 years was higher than that in patients with IH-HSBP older than 65 years. Conclusion: IH-HSBP was associated with an increased risk of diabetic nephropathy among type 2 diabetes mellitus patients with normal or mildly increased albuminuria in the medium to long term. The results support and strengthen previous reports. These findings suggest that IH-HSBP might be a useful marker in disease prognostication

Impact of sustained hypertension on new cardiovascular events in patients with type 2 diabetes: KAMOGAWA‐HBP study

Abstract We have previously shown that masked hypertension (MH) and sustained hypertension (SH) contribute to the progression of diabetic nephropathy. Although the risk of target organ damage and cardiovascular events in MH and SH is significantly higher than that in normotension and white coat hypertension, the role of MH or SH in cardiovascular events has never been reported in studies specific to diabetic patients. Therefore, in this study, we aimed to determine whether blood pressure control status contributes to the development of new cardiovascular events. A longitudinal study of 1082 patients with type 2 diabetes mellitus and no history of cardiovascular events was conducted. Patients were instructed to have their blood pressure measured three times, every morning and evening, for 14 consecutive days. Hypertension status was classified into four groups based on the systolic blood pressure measurements in the clinic and at home. The primary endpoint was the first cardiovascular event. After a median follow‐up of 7.0 (interquartile range, 4.0–9.0) years, 119 patients developed cardiovascular events. The hazard ratio (95% confidence interval) for the risk of developing cardiovascular events was significantly higher in the SH group than in the controlled blood pressure group (1.63 [1.02–2.59]). SH is a useful predictor of cardiovascular events. Both at home and in the clinic, blood pressure monitoring should be assessed in routine clinical practice to predict future cardiovascular events in patients with type 2 diabetes