Mouse mesenchymal stem cells inhibit high endothelial cell activation and lymphocyte homing to lymph nodes by releasing TIMP-1.

Mesenchymal stem cells (MSC) represent a promising therapeutic approach in many diseases in view of their potent immunomodulatory properties, which are only partially understood. Here, we show that the endothelium is a specific and key target of MSC during immunity and inflammation. In mice, MSC inhibit activation and proliferation of endothelial cells in remote inflamed lymph nodes (LNs), affect elongation and arborization of high endothelial venules (HEVs) and inhibit T-cell homing. The proteomic analysis of the MSC secretome identified the tissue inhibitor of metalloproteinase-1 (TIMP-1) as a potential effector molecule responsible for the anti-angiogenic properties of MSC. Both in vitro and in vivo, TIMP-1 activity is responsible for the anti-angiogenic effects of MSC, and increasing TIMP-1 concentrations delivered by an Adeno Associated Virus (AAV) vector recapitulates the effects of MSC transplantation on draining LNs. Thus, this study discovers a new and highly efficient general mechanism through which MSC tune down immunity and inflammation, identifies TIMP-1 as a novel biomarker of MSC-based therapy and opens the gate to new therapeutic approaches of inflammatory diseases

Are Changes in Serum IgG Glycosylation Related to the Severe Course of SARS-CoV-2 Infection and Recovery Process? In Search of New Diagnostic and Prognostic Biomarkers

Katarzyna Sołkiewicz,1 Izabela Kokot,1 Violetta Dymicka-Piekarska,2 Justyna Dorf,2 Ewa Maria Kratz1 1Department of Laboratory Diagnostics, Division of Laboratory Diagnostics, Faculty of Pharmacy, Wroclaw Medical University, Wroclaw, Poland; 2Department of Clinical Laboratory Diagnostics, Medical University of Bialystok, Bialystok, PolandCorrespondence: Ewa Maria Kratz; Katarzyna Sołkiewicz, Email [email protected]; [email protected]: Immunoglobulin G (IgG) glycosylation affects its effector functions and is essential in many steps of the inflammatory cascade. Therefore, it may be an important parameter for assessing the body’s immune response during the course of COVID-19 (Coronavirus disease 2019).Methods: The N- and O-glycosylation of serum IgG in severe COVID-19 patients (n=87), convalescents (n=50), and healthy subjects (n=65) were examined using a modified lectin-ELISA method with specific biotinylated lectins. The obtained data were analyzed using STATISTICA 13.3PL software.Results: We showed significantly higher expression of Lewisx oligosaccharide structures in severe COVID-19 patients than in the other two groups. Moreover, significantly lower expression of Lewisy sugar structures in IgG glycans was observed in the convalescents when compared with COVID-19 patients and healthy subjects. The lowest expression of highly branched N-glycans in cases of severe COVID-19 indicates that the development of the disease is associated with the presence of typical IgG biantennary N-glycans. The lack of significant differences in the expression of Tn antigen in IgG between studied groups and the significantly lower expression of T antigen in convalescents compared to the patients with severe COVID-19 and healthy subjects indicates a decrease in the content of the T antigen in IgG O-glycans in subjects recovered from COVID-19. Substantially higher reactivities of IgG O-glycans with Jacalin observed in COVID-19 patients and convalescents in comparison to the control group were most probably caused by increased expression of core 3 O-glycans in IgG.Conclusion: Severe COVID-19 is accompanied by the expression in serum IgG of sialylated biantennary and highly branched N-glycans, decorated by fucose of Lewisx and Lewisy structures. The higher reactivity of IgG O-glycans with Jacalin in severe COVID-19 patients and convalescents indicates that the disease development and the recovery process are most probably accompanied by increased expression of the core 3 O-glycans.Keywords: serum IgG, glycosylation, SARS-CoV-2, COVID-19, inflammatio

Clinical usefulness of MMP-2 and TIMP-2 concentrations in the preoperative serum of patients with colorectal cancer

Purpose: To evaluate the clinical significance of MMP-2 and TIMP-2 concentrations in the sera of patients diagnosed with colorectal cancer. Methods: The study group comprised 48 patients with colorectal carcinoma and 24 healthy controls. The serum concentration of MMP-2 and TIMP-2 proteins was evaluated by the ELISA method. Results: The mean level of MMP-2 in the sera of patients with colorectal cancer was 39.4 ng/ml and was significantly lower compared with the control (p<0.001). A decrease in TIMP-2 protein in the sera of patients with colorectal cancer was also observed where its mean level was 132.3 ng/ml. The concentration of MMP-2 and TIMP-2 did not correlated with any clinicopathological parameters, except for the patients’ age. In addition, the concentration of MMP-2 in the sera of patients with CRC correlated negatively with the number of white blood cells in the blood and the prothrombin index. The concentration of TIMP-2 correlated positively with potassium and urea concentration in the blood. Conclusions: The results of our study indicate lack of clinical usefulness of determining the levels of MMP-2 and TIMP-2 in the sera of patients with colorectal cancer. However, these proteins play an important role in the carcinogenesis of colorectal cancer