Background/Objectives: Soluble ST2 (sST2) has gained recognition as a clinically relevant biomarker across a spectrum of inflammatory, cardiovascular, and respiratory conditions. However, the lack of assay standardization raises concerns about result comparability across platforms and studies. Methods: This study systematically evaluated serum sST2 concentrations measured with two ELISA systems—DuoSet and Quantikine—produced by the same manufacturer (R&D Systems, Minneapolis, MN, USA). Results: Using archived serum samples from healthy volunteers and marathon runners, we identified marked discrepancies: serum sST2 concentrations using the DuoSet recombinant standard were on average 4.3-fold higher than those using Quantikine (median 308.3 [106.6–608.6] vs. 71.5 [41.8–115.6] ng/mL). On the pre-coated Quantikine plate, using the DuoSet recombinant standard increased calculated concentrations 4.3-fold compared with the native Quantikine standard (median 308.3 [106.6–608.6] vs. 71.5 [41.8–115.6] ng/mL). On the manually coated DuoSet plate, the DuoSet standard yielded higher medians than the Quantikine standard (8.0 [5.6–11.3] vs. 5.0 [3.7–7.4] ng/mL). Furthermore, between-lot variability within the same ELISA platform resulted in concentration shifts from 0.09 [0.07–0.10] ng/mL (2016) to 1.17 [0.81–3.23] ng/mL (2023) using the same sample. Previously published studies also exhibited wide inter-study variability among healthy cohorts. Conclusions: These findings emphasize that current ELISA systems for sST2 are not standardized and that cross-study comparisons should be interpreted with caution. Until universal standardization is implemented, sST2 should primarily be used for within-study comparisons. This variability may limit the reliability of longitudinal sST2 assessment even in clinical settings.

Burn injuries often lead to severe complications, including acute respiratory distress syndrome (ARDS), driven in part by systemic inflammation and glycocalyx disruption. In this study, we analyzed the sera of 28 patients after burn trauma and utilized single-cell RNA sequencing (scRNA-seq) along with microarray transcriptomic analysis to decipher the impact of burn injury on glycocalyx derangement. We observed the significant upregulation of immune cell-derived degrading enzymes, particularly matrix metalloproteinase-8 (MMP8), which correlated with increased immune cell infiltration and glycocalyx derangement. Serum analyses of burn patients revealed significantly elevated levels of shed glycocalyx components and MMP8, both correlating with the presence of inhalation injury. Consequently, the treatment of human in vitro lung tissue models with MMP8 induced significant glycocalyx shedding in alveolar epithelial cells. Together, based on these findings, we propose that MMP8 plays a previously unrecognized role in glycocalyx disruption and subsequent lung injury post-burn, which implies that inhibiting MMP8 may represent a promising therapeutic strategy for alleviating lung injury after burn trauma.

Marathon running exerts physical stress and may lead to transient immune dysregulation, increasing susceptibility to airway inflammation and exercise-induced bronchoconstriction (EIB). This study investigated systemic levels of antimicrobial peptides in athletes and their association with EIB. Serum concentrations of angiogenin, human beta-defensin 2 (hBD-2), major basic protein (MBP), S100A8, and S100A8/A9 were measured in 34 marathoners and 36 half-marathoners at baseline, immediately after a race, and seven days postrace using enzyme-linked immunosorbent assays and compared with 30 sedentary controls. Lung function was assessed by spirometry to identify bronchoconstriction. Levels of hBD-2 and S100A8/A9 were significantly elevated postrace in runners compared to baseline and controls, returning to baseline during recovery. During recovery, S100A8 levels remained slightly elevated in marathoners with EIB. Similarly, human beta-defensin 2 was modestly increased in runners who developed bronchoconstriction. Notably, S100A8 levels correlated negatively with lung function parameters, including forced expiratory volume and mid-expiratory flows. These findings suggest that endurance running induces systemic inflammatory responses and modulates innate immune peptides, particularly in individuals prone to bronchoconstriction. These peptides may serve as biomarkers of respiratory stress and help guide personalized strategies in endurance sports.

Marathon running exerts physical stress and may lead to transient immune dysregulation, increasing susceptibility to airway inflammation and exercise-induced bronchoconstriction (EIB). This study investigated systemic levels of antimicrobial peptides in athletes and their association with EIB. Serum concentrations of angiogenin, human beta-defensin 2 (hBD-2), major basic protein (MBP), S100A8, and S100A8/A9 were measured in 34 marathoners and 36 half-marathoners at baseline, immediately after the race, and seven days post-race using enzyme-linked immunosorbent assays and compared with 30 sedentary controls. Lung function was assessed by spirometry to identify bronchoconstriction. Levels of hBD-2 and S100A8/A9 were significantly elevated post-race in runners compared to baseline and controls, returning to baseline during recovery. During recovery, S100A8 levels remained slightly elevated in marathoners with EIB. Similarly, human beta-defensin 2 was modestly increased in runners who developed bronchoconstriction. Notably, S100A8 levels correlated negatively with lung function parameters, including forced expiratory volume and mid-expiratory flows. These findings suggest that endurance running induces systemic inflammatory responses and modulates innate immune peptides, particularly in individuals prone to bronchoconstriction. These peptides may serve as biomarkers of respiratory stress and help guide personalized strategies in endurance sports.