👤 Michal Lis

Lipoprotein(a) [Lp(a)] is a highly atherogenic particle that significantly increases overall cardiovascular risk. Evidence regarding concentrations of Lp(a) in the Polish general population remains limited, as well as the association between Lp(a) and various clinical characteristics. The aim in this study was to analyze Lp(a) concentration in a Polish population hospitalized in a tertiary referral hospital, compare clinical characteristics between patients with low and high Lp(a) and find the predictors of increased Lp(a) concentrations. This was an observational, cross-sectional study. All patients hospitalized in the Clinical Department of Internal Medicine, Endocrinology, Diabetology, and Nephrology in the Czerniakowski Hospital between 01.03.2024 and 08.10.2024 and with measured Lp(a) concentration were consecutively included. Patients were divided into two groups: those with high Lp(a) (≥ 30 mg/dL) and those with low Lp(a) ( < 30 mg/dL). The groups were compared in terms of multiple clinical characteristics. Multiple logistic regression was used to determine independent predictors of high Lp(a). The p-value below 0.05 was considered statistically significant. Out of 562 patients, 117 had high Lp(a) concentration (20.8%). The groups did not differ in terms of age, sex, or clinical examination findings. In a multiple logistic regression, male sex was associated with a decreased odds ratio of high Lp(a) (OR = 0.2857, 95% CI: 0.1107 to 0.6468, p = 0.01). High Lp(a) is prevalent in the Polish population, and thus it is important to measure it routinely in each individual at least once in a lifetime and control all other known cardiovascular risk factors to decrease the overall risk. Show less

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in Poland. Lipoprotein(a) [Lp(a)] constitutes an independent, causal risk factor for ASCVD and aortic valve stenosis. Elevated Lp(a) is found in approximately 20% of the Polish population. Lp(a) measurements have been recommended in all adult patients to improve cardiovascular risk stratification. As the testing rate remains insufficient, there is a need to facilitate the incorporation of Lp(a) into routine patient care. This clinically oriented review outlines (i) up-to-date evidence on the role of Lp(a) in cardiovascular diseases, (ii) recent real-world data on the characteristics of Polish patients with elevated Lp(a), and (iii) strategies for Lp(a) testing and management in light of the current national recommendations and the latest 2025 Focused Update of the 2019 ESC/EAS Guidelines for the management of dyslipidemias. Show less

Lysosomes are implicated in a wide spectrum of human diseases, including monogenic lysosomal storage disorders (LSDs), age-associated neurodegeneration, and cancer. Profiling lysosomal content using tag-based lysosomal immunoprecipitation (LysoTagIP) in cell and animal models has substantially moved the field forward, but studying lysosomal dysfunction in patients remains challenging. Here, we report the development of the 'tagless LysoIP' method, designed to enable the rapid enrichment of lysosomes, via immunoprecipitation, using the endogenous integral lysosomal membrane protein TMEM192, directly from clinical samples and human cell lines (e.g., induced pluripotent stem cell-derived neurons). Isolated lysosomes were intact and suitable for subsequent multimodal omics analyses. To validate our approach, we applied the tagless LysoIP to enrich lysosomes from peripheral blood mononuclear cells derived from fresh blood of healthy donors and patients with CLN3 disease, an autosomal recessive neurodegenerative LSD. Metabolic profiling of isolated lysosomes revealed massive accumulation of glycerophosphodiesters (GPDs) in patients' lysosomes. Interestingly, a patient with a milder phenotype and genotype displayed lower accumulation of lysosomal GPDs, consistent with their potential role as disease biomarkers. Altogether, the tagless LysoIP provides a framework to study native lysosomes from patient samples, identify disease biomarkers, and discover human-relevant disease mechanisms. Show less

Allergen-specific immunotherapy (AIT) is the only disease-modifying treatment in allergic airway diseases. Underlying immunological mechanisms and candidate biomarkers, which may be translated into predictive/surrogate measures of clinical efficacy, remain an active area of research. The aim of this study was to evaluate Pollinex Quattro (PQ) Grass AIT induced immunomodulatory mechanisms, based on transcriptome profiling of peripheral blood mononuclear cells. 119 subjects with grass pollen induced seasonal allergic rhinitis (SAR) were randomized in a 2:2:1:1 ratio to receive a cumulative dose of PQ Grass as a conventional or extended pre-seasonal regimen, placebo, or placebo with MicroCrystalline Tyrosine. Gene expression analysis was an exploratory endpoint evaluated in a subgroup of 30 subjects randomly selected from the four treatment arms. Samples were collected at three time points: screening (baseline), before the start of the grass pollen season and at the end of the season. This study was funded by the manufacturer of PQ. Transcriptome analysis demonstrated that the most significant changes in gene expression, for both treatment regimens, were at the end of the grass pollen season, with the main Th1 candidate molecules (IL-12A, IFNγ) upregulated and Th2 signature cytokines downregulated (IL-4, IL-13, IL-9) (p < .05). Canonical pathways analysis demonstrated Th1, Th2, Th17 and IL-17 as the most significantly enriched pathways based on absolute value of activation z-score (IzI score ≥ 2, p < .05). Upstream regulator analysis showed pronounced inhibition of pro-inflammatory allergic molecules IgE, IL-17A, IL-17F, IL-25 (IL-17E) (IzI score ≥ 2, FDR < 0.05) and activation of pro-tolerogenic molecules IL-12A, IL-27, IL-35 (EBI3) at the end of the grass pollen season. Peripheral blood mononuclear cells transcriptome profile showed an inhibition of Th2, Th17 pro-inflammatory allergic responses and immune deviation towards Th1 responses. PQ Grass extended regimen exhibited a superior mechanistic efficacy profile in comparison with PQ conventional regimen. Show less