Leukocyte Depletion in Allogeneic Blood Transfusion Does Not Change the Negative Influence on Survival Following Transthoracic Resection for Esophageal Cancer

Background: Perioperative transfusion of allogeneic blood has been hypothesized to have an immunomodulatory effect and influence survival in several cancer types. This study evaluates the association between receipt of leucocyte-depleted and non-depleted allogeneic blood and survival following esophagectomy for cancer. Methods: A retrospective analysis was performed including 291 patients with esophageal cancers who underwent transthoracic en bloc esophagectomy and extended mediastinal lymphadenectomy. Neoadjuvant chemoradiation was administered in 152 (52.2%) patients. Perioperative blood transfusions were quantified and the potential prognostic cutoff for transfused units was calculated according to LeBlanc. Results: The median number of perioperative blood transfusions was 2 (0-24), and 106 patients (36.4%) received no transfusions. Patients with one or less blood transfusion showed a significantly improved survival compared to patients receiving more than one unit (p < 0.009). In multivariate analysis, blood transfusion categories showed significance (p < 0.015) next to pT, pN, pM category, and residual tumor categories (R-categories). Separate analysis of 183 patients treated after the mandatory introduction of leukocyte-depleted blood transfusions detected a strong tendency, but no significant difference in survival for patients getting one or less or more than one transfusion (p = 0.056). Receipt of leukocyte-depleted versus non-depleted units, however, had no influence on survival (p = 0.766). Conclusions: The need for perioperative allogeneic blood transfusions is significantly associated with poorer survival following resection for esophageal cancer by univariate and multivariate analysis. Our data suggest that the reduction of leukocytes in allogeneic transfusions is not sufficient to overcome the negative influence on surviva

Function, expression and localization of annexin A7 in platelets and red blood cells: Insights derived from an annexin A7 mutant mouse

BACKGROUND: Annexin A7 is a Ca(2+)- and phospholipid-binding protein expressed as a 47 and 51 kDa isoform, which is thought to be involved in membrane fusion processes. Recently the 47 kDa isoform has been identified in erythrocytes where it was proposed to be a key component in the process of the Ca(2+)-dependent vesicle release, a process with which red blood cells might protect themselves against an attack by for example complement components. RESULTS: The role of annexin A7 in red blood cells was addressed in erythrocytes from anxA7(-/-) mice. Interestingly, the Ca(2+)-mediated vesiculation process was not impaired. Also, the membrane organization appeared not to be disturbed as assessed using gradient fractionation studies. Instead, lack of annexin A7 led to an altered cell shape and increased osmotic resistance of red blood cells. Annexin A7 was also identified in platelets. In these cells its loss led to a slightly slower aggregation velocity which seems to be compensated by an increased number of platelets. The results appear to rule out an important role of annexin A7 in membrane fusion processes occurring in red blood cells. Instead the protein might be involved in the organization of the membrane cytoskeleton. Red blood cells may represent an appropriate model to study the role of annexin A7 in cellular processes. CONCLUSION: We have demonstrated the presence of both annexin A7 isoforms in red blood cells and the presence of the small isoform in platelets. In both cell types the loss of annexin A7 impairs cellular functions. The defects observed are however not compatible with a crucial role for annexin A7 in membrane fusion processes in these cell types

Ultrastructure of human platelet concentrates after treatment with pathogen reduction technologies for prolonged storage

Background and objectivesPathogen reduction technologies (PRTs) increase blood supply safety but may also increase platelet storage lesion, probably due to mitochondrial DNA damage. The purpose of this study was to investigate whether these changes are morphologically detectable.Materials and methodsBlood platelets were obtained by triple-dose apheresis collection (n = 8). Immediately after splitting, single units were left untreated (CONTROL) or treated with either psoralen-UVA (INTERCEPT) or riboflavin-UVB (MIRASOL). All platelet units were resuspended in platelet additive solution (INTERSOL or SSP+) and stored for up to seven days. Seven samples from each donation were examined by electron microscopy fresh, i.e., immediately after collection, and after1 day and 7 days of storage either untreated or treated with INTERCEPT or MIRASOL PRT. The volumes of mitochondria and of the canalicular system (CS) were measured.ResultsFreshly isolated platelets (0 days storage) contained 2.4% mitochondria (volume density) and 4.5% CS (volume density). After 1 day of storage mitochondrial volume density was reduced to 1.5% in untreated, 1.3% in INTERCEPT-treated and 1.6% in MIRASOL-treated platelet concentrates, i.e., a loss of up to 37% of mitochondrial volume regardless of treatment. After 7 days storage mitochondrial volume density was 1.3, 1.3 and 1.5% respectively; neither at 1 nor at 7 days storage were any noteworthy differences between untreated, INTERCEPT or MIRASOL-treated platelets. In stark contrast to mitochondria the CS ballooned up to 88% in all groups. After 1 day of storage CS volume density was increased to 8.6% in untreated, 8.4% in INTERCEPT-treated and 7.0% in MIRASOL-treated platelet concentrates. After 7 days storage CS volume density was 8.0, 8.3 and 6.3% respectively; neither at 1 nor at 7 days storage were significant differences between untreated, INTERCEPT or MIRASOL-treated platelets. Only at 7 days a slight tendency of a smaller CS in MIRASOL versus INTERCEPT and untreated CONTROL groups was observed.ConclusionPlatelet mitochondrial volume shrinks and canalicular system swells within the first 24 h after collection and then both remain rather constant for up to seven days with or without PRT treatment. Pathogen reduction technology – both INTERCEPT and MIRASOL – does not increase morphological platelet storage lesion

Implication of IL-2/IL-21 region in systemic sclerosis genetic susceptibility

Objective: The interleukin 2 (IL-2) and interleukin 21 (IL-21) locus at chromosome 4q27 has been associated with several autoimmune diseases, and both genes are related to immune system functions. The aim of this study was to evaluate the role of the IL-2/IL-21 locus in systemic sclerosis (SSc). Patients and methods: The case control study included 4493 SSc Caucasian patients and 5856 healthy controls from eight Caucasian populations (Spain, Germany, The Netherlands, USA, Italy, Sweden, UK and Norway). Four single nucleotide polymorphisms (rs2069762, rs6822844, rs6835457 and rs907715) were genotyped using TaqMan allelic discrimination assays. Results: We observed evidence of association of the rs6822844 and rs907715 variants with global SSc (pc=6.6E-4 and pc=7.2E-3, respectively). Similar statistically significant associations were observed for the limited cutaneous form of the disease. The conditional regression analysis suggested that the most likely genetic variation responsible for the association was the rs6822844 polymorphism. Consistently, the rs2069762A-rs6822844T-rs6835457G-rs907715T allelic combination showed evidence of association with SSc and limited cutaneous SSc subtype (pc=1.7E-03 and pc=8E-4, respectively). Conclusions: These results suggested that the IL-2/IL-21 locus influences the genetic susceptibility to SSc. Moreover, this study provided further support for the IL-2/IL-21 locus as a common genetic factor in autoimmune diseases