Antigen-Specific versus Non-Antigen-Specific Immunoadsorption in ABO-Incompatible Renal Transplantation

Introduction: ABO-incompatible (ABOi) renal transplantation (RTx) from living donors is an established procedure to expand the donor pool for patients with end stage renal disease. Immunoadsorption (IA) is a standard procedure for the removal of preformed antibodies against the allograft. In this study, antigen-specific and non-antigen-specific IA in ABOi RTx were compared. Patients and Methods: 10 patients underwent antigen-specific IA (Glycosorb group) and 13 patients non-antigen-specific IA (Immunosorba group). The effects of both procedures regarding antibody reduction, number of treatments, complications, costs, as well as the allograft function and patient survival were compared between both groups. Results: Although the IgG levels were reduced equally by both procedures (p=0.82), the reduction of the IgM level was more effective in the Glycosorb group (p=0.0172). Patients in both groups required a median number of 6 IA before ABOi RTx. Allograft function at one year after AB0i RTx was similar in both groups (estimated glomerular filtration rate: 66 vs. 64 ml/min/1.73m² respectively), with a death-censored graft survival of 90.0% and 92.3% respectively. Complication rates did not differ between procedures. Due to the reuse of non-antigen-specific Immunosorba columns, costs were considerably lower in this group; however, the use of the Immunosorba-based IA was less time-efficient. Conclusion: Considering upcoming alternatives as simultaneous performance of dialysis and IA or a possible reuse of Glycosorb columns, this might become less relevant in the future

Telomere Length Is Not Related to Established Cardiovascular Risk Factors but Does Correlate with Red and White Blood Cell Counts in a German Blood Donor Population.

Telomere length (TL) is considered a marker of biological aging and has been associated with the presence of various coronary risk factors in patients. Much less is known about the relationships between TL and classic coronary risk factors in other populations. We measured TL in peripheral blood leukocytes of 343 middle-aged blood donors (mean age 40.2 ± 12.4 years; 201 men, 142 women) using quantitative polymerase chain reaction. Median TL was 0.86 (range: 0.48-1.85) relative TL units. In linear regression analyses with natural log-transformed T to S ratio as the dependent variable, there was a significant association with age (per year: beta = -0.007, p<0.001) and sex (males vs. females: beta = 0.075, p = 0.007) with longer telomeres in men. After adjusting for these two variables, we observed no association of TL with classic coronary risk factors including cholesterol (p = 0.36), triglyceride (p = 0.09), HDL-cholesterol (p = 0.26), LDL-cholesterol (p = 0.36), smoking (p = 0.97), and personal (p = 0.46) or family history (p = 0.63) of cardiovascular disease. However, we did find a significant positive association with white (p = 0.011) and red blood cell count (p = 0.031), hemoglobin (p = 0.014) and hematocrit (p = 0.013); we also found a borderline positive association with thrombocytes (p = 0.074). Positive associations remained significant for hemoglobin (p = 0.017), hematocrit (p = 0.023), and leukocytes (p = 0.009) in a subgroup with no reported vascular disease; associations were of borderline significance for erythrocytes (p = 0.053) and thrombocytes (p = 0.088) in this subgroup. The data do not support the concept that classic coronary risk factors contribute to telomere attrition in a blood donor population. However, telomere attrition may be a marker for reduced proliferation reserve in hematopoietic progenitor cells

Influence of risk factors on telomere length (natural log-transformed T/S ratio), results of linear regression models, n = 343.

<p>#: adjustments for age and sex</p><p>CI = confidence interval</p><p>† = one outlier removed before regression analyses</p><p>BMI = Body mass index</p><p>LDL = low density lipoprotein</p><p>HDL = high density lipoprotein</p><p>GOT = Glutamat-Oxalacetat-Transaminase</p><p>GPT = Glutamat-Pyruvat-Transaminase</p><p>MCV = Mean corpuscular volume</p><p>MCH = Mean corpuscular hemoglobin</p><p>MCHC = Mean corpuscular hemoglobin concentration</p><p>## = Hyperfibrinogenemia and/or obesity and/or triglycerides > 150 mmol/L combined with HDL < 50 mmol/L (♀) resp. < 40 mmol/L (♂).</p><p>Influence of risk factors on telomere length (natural log-transformed T/S ratio), results of linear regression models, n = 343.</p

Influence of risk factors on telomere length (natural log-transformed T/S ratio), results of linear regression models in patients without vascular disease, n = 324.

<p>#: adjustments for age and sex</p><p>CI = confidence interval</p><p>† = one outlier removed before regression analyses</p><p>BMI = Body mass index</p><p>LDL = low density lipoprotein</p><p>HDL = high density lipoprotein</p><p>GOT = Glutamat-Oxalacetat-Transaminase</p><p>GPT = Glutamat-Pyruvat-Transaminase</p><p>MCV = Mean corpuscular volume</p><p>MCH = Mean corpuscular hemoglobin</p><p>MCHC = Mean corpuscular hemoglobin concentration</p><p>## = Hyperfibrinogenemia and/or obesity and/or triglycerides > 150 mmol/L combined with HDL < 50 mmol/L (♀) resp. < 40 mmol/L (♂).</p><p>Influence of risk factors on telomere length (natural log-transformed T/S ratio), results of linear regression models in patients without vascular disease, n = 324.</p

Syndecan-1 (CD138) Modulates Triple-Negative Breast Cancer Stem Cell Properties via Regulation of LRP-6 and IL-6-Mediated STAT3 Signaling

Syndecan-1 (CD138), a heparan sulfate proteoglycan, acts as a coreceptor for growth factors and chemokines and is a molecular marker associated with epithelial-mesenchymal transition during development and carcinogenesis. Resistance of Syndecan-1-deficient mice to experimentally-induced tumorigenesis has been linked to altered Wnt-responsive precursor cell pools, suggesting a potential role of Syndecan-1 in breast cancer cell stem function. However, the precise molecular mechanism is still elusive. Here, we decipher the functional impact of Syndecan-1 knockdown using RNA interference on the breast cancer stem cell phenotype of human triple-negative MDA-MB-231 and hormone receptor-positive MCF-7 cells in vitro employing an analytical flow cytometric approach. Successful Syndecan-1 siRNA knockdown was confirmed by flow cytometry. Side population measurement by Hoechst dye exclusion and Aldehyde dehydrogenase-1 activity revealed that Syndecan-1 knockdown in MDA-MB-231 cells significantly reduced putative cancer stem cell pools by 60 % and 27%, respectively, compared to controls. In MCF-7 cells, Syndecan-1 depletion reduced the side population by 40 % and Aldehyde dehydrogenase-1 by 50%, repectively. In MDA-MB-231 cells, the CD44(+)CD24(-/low) phenotype decreased significantly by 6 % upon siRNA-mediated Syndecan-1 depletion. Intriguingly, IL-6, its receptor sIL-6R, and the chemokine CCL20, implicated in regulating stemness-associated pathways, were downregulated by&gt;40 % in Syndecan-1-silenced MDA-MB-23

Costs for immunoadsorption.

<p>All prices are shown in Euro. Expenses do not include replacement fluids and labor costs.</p><p>Costs for immunoadsorption.</p