Previously, we reported a novel disease of impaired glycosaminoglycans (GAGs) metabolism without deficiency of known lysosomal enzymes—mucopolysaccharidosis-plus syndrome (MPSPS). MPSPS, whose pathophysiology is not elucidated, is an autosomal recessive multisystem disorder caused by a specific mutation p.R498W in the VPS33A gene. VPS33A functions in endocytic and autophagic pathways, but p.R498W mutation did not affect both of these pathways in the patient’s skin fibroblast. Nineteen patients with MPSPS have been identified: seventeen patients were found among the Yakut population (Russia) and two patients from Turkey. Clinical features of MPSPS patients are similar to conventional mucopolysaccharidoses (MPS). In addition to typical symptoms for conventional MPS, MPSPS patients developed other features such as congenital heart defects, renal and hematopoietic disorders. Diagnosis generally requires evidence of clinical picture similar to MPS and molecular genetic testing. Disease is very severe, prognosis is unfavorable and most of patients died at age of 10–20 months. Currently there is no specific therapy for this disease and clinical management is limited to supportive and symptomatic treatment.

Mucopolysaccharidoses (MPS) are rare lysosomal storage disorders (LSD) characterized by the excessive accumulation of glycosaminoglycans (GAG). Conventional MPS, caused by inborn deficiencies of lysosomal enzymes involved in GAG degradation, display various multisystemic symptoms—including progressive neurological complications, ophthalmological disorders, hearing loss, gastrointestinal and hepatobiliary issues, cardiorespiratory problems, bone and joint abnormalities, dwarfism, and coarse facial features. Mucopolysaccharidosis-Plus Syndrome (MPSPS), an autosomal recessive disease caused by a mutation in the endo-lysosomal tethering protein VPS33A, shows additional renal and hematopoietic abnormalities (“Plus symptoms”) uncommon in conventional MPS. Here, we analyze data from biochemical, histological, and physical examinations—particularly of blood counts and kidney function—to further characterize the clinical phenotype of MPSPS. A series of blood tests indicate hematopoietic symptoms including progressive anemia and thrombocytopenia, which correlate with histological observations of hypoplastic bone marrow. High urinary excretion of protein (caused by impairments in renal filtration), hypoalbuminemia, and elevated levels of creatinine, cholesterol, and uric acid indicate renal dysfunction. Histological analyses of MPSPS kidneys similarly suggest the extensive destruction of glomerular structures by foamy podocytes. Height and weight did not significantly deviate from the average, but in some cases, growth began to decline at around six months or one year of age.

Background: Tumor necrosis factor (TNF)-α is an inflammatory cytokine, the biological effects of which are mediated by the interaction with specific membrane-bound receptors. To assess TNF-α receptor (TNFR) expression, it is important to estimate both the number of cells that carry these receptors and the number of receptors per cell, because the cell fate depends on the balance between TNFRI and TNFRII signaling. Objective: The aim of the present study was to develop an optimized protocol to estimate the level of expression of membrane-bound TNFRI and TNFRII, using QuantiBRITE PE calibration beads. Materials and methods: The percentage of cells that expressed membrane-bound TNFRI and TNFRII and the mean number of receptors per cell were determined by flow cytometry using PE-labeled antibodies against TNFR. To create a calibration curve and convert cell fluorescence intensity values to absolute numbers of receptors, we used QuantiBRITE PE beads. Results: CD19⁺ B lymphocytes had the least percentage of cells expressing TNFRI and the greatest number of receptor molecules per cell, whereas CD3⁺ T lymphocytes had the greatest percentage of cells expressing TNFRII and the lowest density of these receptors. We also established that stimulation of peripheral blood mononuclear cells (PBMCs) with the lipopolysaccharide (LPS) significantly increased the number of TNFRI and TNFRII on CD14⁺ monocytes. Conclusion: Application of the protocol-identified differences in the percentage of cells that expressed TNFRs, as well as the absolute number of receptors per cell, among different subpopulations of PBMCs, and between PBMCs cultured with and without LPS.

Since the first report of SOPH syndrome among the Yakut population in 2010, new clinical data of SOPH‐like conditions continue to appear. We expand the phenotypic spectrum of SOPH syndrome and perform a comparative analysis of Yakut SOPH patients' clinical data with SOPH‐like conditions reported in the world scientific literature to form a foundation for NBAS pathogenesis discussion. Clinical data from the genetic records of 93 patients with SOPH syndrome and global survey data on patients with pathogenic variants of the C‐terminal in the NBAS gene were collected. A detailed phenotype description of patients is presented with a total number of 111 individuals. Underweight below the fifth centile and prone to delayed bone age in Yakut SOPH patients are retrospectively observed. We outline the short stature with optic atrophy as the leading phenotyping trait for C‐terminal NBAS patients. The pathophysiology and patients management of SOPH‐like conditions are discussed.

Introduction: Immunosenescence alters TNF receptor expression (TNFR1 and TNFR2), contributing to chronic inflammation (inflamm-aging) and age-related diseases. Polymorphisms in TNFRSF1A and TNFRSF1B may influence receptor expression; however, their role in age-dependent modulation remains unclear. This study examines TNFR1/TNFR2 expression dynamics on T cells, B cells, and monocytes across different ages and evaluates the impact of genetic polymorphisms. Methods: PBMCs from 150 donors (18–60 years) were isolated via density-gradient centrifugation and cultured under spontaneous and LPS-stimulated conditions. TNFR1 and TNFR2 expression on immune cell subsets was quantified using flow cytometry with BD QuantiBRITE PE beads. SNP genotyping in TNFRSF1A and TNFRSF1B was performed via PCR with restriction analysis. Nonlinear age-related trends were assessed using polynomial approximation and inflection point analysis (Tukey’s method). Results: Among the 23 analyzed TNF system parameters, the proportion of TNFR2⁺CD3⁺ T cells increased with age, whereas TNFR1⁺ and TNFR2⁺ monocyte populations showed significant negative correlations (p < 0.05). Inflection points (~27, 34–36, and 44–45 years) indicated nonlinear dynamics in TNFRs expression during aging. TNFR2 expression on T cells gradually increased and stabilized at later ages, whereas TNFR1 and TNFR2 expression on monocytes followed distinct declining trajectories. Genetic polymorphisms influenced correlation strength, but did not alter direction, demonstrating a conserved pattern of age-related receptor expression shifts. Conclusions: TNFR expression exhibits nonlinear, age-dependent alterations across immune cells, shaped by immunosenescence and genetic variability. The identified critical age intervals represent key phases of immune remodeling, where assessing TNFR expression may provide insights into inflamm-aging mechanisms and potential targets for immune modulation.