Hyperphosphatemia is a significant risk factor for the development of ectopic calcification and coronary artery diseases in patients on hemodialysis (HD), and must be controlled with the use of phosphate binders. Studies comparing the effects of sevelamer and nicotinic acid, both similar non-calcium and non-aluminum phosphate binders, are not available. In this study, 40 patients on HD with a serum phosphorus level of more than 6 mg/dL were enrolled. After a two week washout period without phosphate binders, the patients were randomly divided into two equal groups (n = 20) and were started on nicotinic acid or sevelamer for a period of four weeks. The dose of nicotinic acid used was 500 mg and that of sevelamer was 1600 mg daily. Blood samples were drawn for the measurement of the total calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), triglyceride (TG), total cholesterol (Chol), high-density lipoprotein (HDL), low-density lipoprotein (LDL), uric acid and parathyroid hormone (PTH). Patients receiving sevelamer showed a significant reduction in serum P level (2.2 ± 0.69 mg/dL; P <0.0001) in comparison with the nicotinic acid group (1.7 ± 1.06 mg/dL; P = 0.004). Reduction in the Ca-P product was significantly different in the two groups; in the sevelamer group, it was 21 ± 7; (P <0.0001) while in the nicotinic acid group, it was 16 ± 11 (P = 0.007). Also, patients on sevelamer showed greater reduction in the mean TG level (38.9 ± 92 mg/dL; P = 0.005). No significant changes were observed in the mean serum Ca, total Chol, HDL, LDL, ALP and iPTH levels in the two study groups. Our short-term study suggests that although nicotinic acid reduced hyperphosphatemia, sevelamer showed higher efficacy in controlling hyperphosphatemia as well as the Ca-P product.

Background/Objectives: Diffuse midline gliomas (DMGs) are among the most aggressive paediatric brain tumours, with the pathognomonic H3K27M mutation present in over 80% of cases. This mutation drives epigenetic dysregulation and transcriptional reprogramming, yet its impact on the tumour antigenic landscape remains poorly understood. Given the low mutational burden of DMG, an expanded search beyond neoantigens to include epigenetically dysregulated tumour-associated antigens (TAAs) is critical for advancing antigen-specific immunotherapies. Methods: We performed immunopeptidomic analysis of two patient-derived H3K27M-mutant DMG cell lines (SU-DIPG13 and BT245) and their isogenic counterparts in which only the mutant H3F3A allele was disrupted by CRISPR editing (H3K27M-KO), leaving wild-type histone H3.3 intact. High-resolution mass spectrometry and bioinformatics were used to define H3K27M-associated changes in the immunopeptidome, and functional T cell assays with HLA-matched healthy donor PBMCs assessed peptide immunogenicity. Results: H3K27M modulated the tumour antigenic landscape in a model-specific manner. Loss of the mutant allele increased HLA-I expression in SU-DIPG13 but not BT245, while immunopeptidomic profiling revealed distinct shifts in tumour-associated peptide presentation in both models, indicating that HLA-I abundance alone does not explain these changes. We identified six peptides derived from SLITRK2, PRAME, XKR5 and CBX2 that elicited T-cell responses in vitro; T cells raised against five of these preferentially recognised the parental H3K27M-mutant DMG cells. Several prioritised peptides were detected only in parental H3K27M-mutant cells, supporting mutation-associated, antigen-selective differences in peptide presentation and tumour antigenicity. Conclusions: This study shows that H3K27M modulates the antigenic landscape in DMG in a model-dependent, antigen-selective manner, uncovering immunogenic tumour-associated peptides that could serve as targets for precision immunotherapy and establishing a foundation for T cell-based therapies in this otherwise treatment-refractory disease.