Peripheral blood mononuclear cell response to YKL-40 and Galectin-3 in cystic fibrosis.

BACKGROUND: Elevated circulating levels of YKL-40 correlate with disease severity in Cystic Fibrosis (CF), but the role of YKL-40 in the inflammatory response in CF is still under investigation. Our main goal was to evaluate if YKL-40 can modulate the expression of major cytokines (IL-6, IL-10, IL-13) implicated in the inflammatory response in CF. A secondary goal was to explore the interactions between YKL-40 and other circulating proteins to determine the impacts on cytokine modulation. METHOD: Peripheral blood mononuclear cells (PBMCs) were isolated from the blood of 83 adult CF patients in stable clinical condition. PBMCs were treated with human YKL-40 followed by the measure of IL-6, IL-10 and IL-13 gene expression. Protein arrays were used to explore the interactions between YKL-40 and circulating proteins. Interaction with Galectin-3 (GAL3) was identified, and confirmed by binding assay. Cytokine gene expressions were again monitored by RT-qPCR after PBMC treatment with GAL3, with or without YKL-40 co-stimulation. RESULTS: Following YKL-40 stimulation, PBMC gene expression of IL-6, IL-10 and IL-13 varies across patients. IL-6 and IL-13 are coexpressed, but this response was different in male and female patients. GAL3 protein was detected in the blood of CF patients, and a molecular interaction with YKL-40 was identified. GAL3 did not interfere with the YKL-40 stimulation of IL-6, IL-10 and IL-13 but may modulate the coexpression. CONCLUSION: We observed that YKL-40 stimulation had a variable impact on IL-6, IL-10, and IL-13 gene expression in CF PBMCs and uncovered an interaction between GAL3 and YKL-40 in the serum of CF patients. Our findings suggest that YKL-40 is not only a biomarker of disease severity in CF, but it might play an active role in the inflammatory pathophysiology of the disease.

Iron-deficiency among blood donors: Donors' opinion on iron supplementation strategy.

BACKGROUND AND OBJECTIVES: Each donation of a single whole blood unit causes a 200-250mg iron loss. The main clinical manifestation of iron deficiency among blood donors is anemia, and every blood collection establishment must have measures in place to minimize and prevent iron depletion in blood donors, according to the European guidelines. However, iron deficiency without anemia is also associated with clinical manifestations. The management of iron deficiency is an acute issue; still, no consensus on its managements exists. One possibility is iron supplementation; however, the acceptability of such a measure is still unknown, so we asked donors' opinions on this topic. MATERIALS AND METHODS: Over a 2-month period, a questionnaire was voluntarily completed by blood donors at the French Military Blood Institute. Gender, age, number of donations in the last 12 months, and preference between iron supplementation and general practitioner consultation for management of iron deficiency were recorded. RESULTS: One thousand nine hundred and seventy-four questionnaires were returned. Donors between ages 18-50 represented 89% of respondents. Altogether, 49% declared that they would rather visit their general practitioner and 46% would rather receive iron supplementation. There were no significant differences correlated with gender or age. However, a higher number of prior donations was significantly associated with a preference for iron supplementation. Frequent female donors had an even stronger preference for iron supplementation. CONCLUSION: Our results showed that there are no strong objections to iron supplementation, which could be an acceptable option for frequent donors - the main population at risk for iron deficiency.

Humoral and cellular immune responses to Fasciola hepatica experimental primary and secondary infection in sheep.

Blood leukocyte changes, serum hepatic enzyme levels, lymphocyte proliferation in response to Concanavalin A (ConA) and to parasitic excretory-secretory products (FhESP), and antibody (IgG and IgM) responses (ELISA and Western blot) were studied in sheep, the natural susceptible host of F. hepatica, during the first 3 months of an experimental primary or secondary infection. The proportion of flukes established was similar in once- and twice-infected groups, but the flukes originating from the secondary infection migrated more rapidly to the bile ducts. Primary infection induced a marked peripheral eosinophilia from 3 to 13 weeks post-primary infection (PPIW). FhESP-specific IgM were produced from PPIW 2 with peaks in PPIW 3 and 9-10; FhESP-specific IgG increased from PPIW 2 to 6 and became stable afterwards. Western blotting revealed 12 major antigenic fractions in FhESP from 12, 15, 20, 24, 27, 28.5, 30, 41, 51, 56, 69 and 156 kDa; some non-specific ones have been characterized. A sequential recognition of higher then lower molecular weight antigens was observed. FhESP-specific lymphocyte proliferation was marked from PPIW 2 to 5. In contrast, ConA stimulation of lymphocytes was decreased. After secondary infection in PPIW 6, immune responses were modified. The ConA-induced lymphocyte proliferation was transitorily increased. In contrast, the humoral response, in particular against the early recognized antigens, and the level and the duration of the FhESP-specific lymphocyte proliferative response, were reduced.