The recognition of pathogen-derived structures by C-type lectins and the chemotactic activity mediated by the CCL2/CCR2 axis are critical steps in determining the host immune response to fungi. The present study was designed to investigate whether the presence of single nucleotide polymorphisms (SNPs) within DC-SIGN, Dectin-1, Dectin-2, CCL2 and CCR2 genes influence the risk of developing Invasive Pulmonary Aspergillosis (IPA). Twenty-seven SNPs were selected using a hybrid functional/tagging approach and genotyped in 182 haematological patients, fifty-seven of them diagnosed with proven or probable IPA according to the 2008 EORTC/MSG criteria. Association analysis revealed that carriers of the Dectin-1 rs3901533 T/T and Dectin-1 rs7309123 G/G genotypes and DC-SIGN rs4804800 G, DC-SIGN rs11465384 T, DC-SIGN 7248637 A and DC-SIGN 7252229 C alleles had a significantly increased risk of IPA infection (OR = 5.59 95%CI 1.37–22.77; OR = 4.91 95%CI 1.52–15.89; OR = 2.75 95%CI 1.27–5.95; OR = 2.70 95%CI 1.24–5.90; OR = 2.39 95%CI 1.09–5.22 and OR = 2.05 95%CI 1.00–4.22, respectively). There was also a significantly increased frequency of galactomannan positivity among patients carrying the Dectin-1 rs3901533_T allele and Dectin-1 rs7309123_G/G genotype. In addition, healthy individuals with this latter genotype showed a significantly decreased level of Dectin-1 mRNA expression compared to C-allele carriers, suggesting a role of the Dectin-1 rs7309123 polymorphism in determining the levels of Dectin-1 and, consequently, the level of susceptibility to IPA infection. SNP-SNP interaction (epistasis) analysis revealed significant interactions models including SNPs in Dectin-1, Dectin-2, CCL2 and CCR2 genes, with synergistic genetic effects. Although these results need to be further validated in larger cohorts, they suggest that Dectin-1, DC-SIGN, Dectin-2, CCL2 and CCR2 genetic variants influence the risk of IPA infection and might be useful in developing a risk-adapted prophylaxis.

Of the sandfly fever viruses known to be human pathogens (serotypes Toscana [TOS], Sicilian [SFS], and Naples [SFN]), only TOS has demonstrated neurotropic activity. Infections by TOS have been reported in Mediterranean countries, but the virus was previously isolated only in Italy and Portugal. We isolated 15 strains of TOS between 1988 and 1996 from the cerebrospinal fluid of patients with acute aseptic meningitis in Granada, Spain. This finding led us to study the presence of antibodies to TOS, SFS, and SFN in 1,181 adults and 87 children from different regions of Spain. We found that the prevalence of antibodies to these viruses was 26.2%, 2.2, and 11.9%, respectively; these rates imply that TOS infections are common in Spain.

The residual risks of transmission of HIV, HBV, and HCV in Spain are similar to those reported in other countries and should be further reduced in the future.

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Summary:The objective of this study was to analyze CD34 + cell recovery and T cell depletion (TCD) achieved in CD34 + cell grafts using either immunoadsorption or immunomagnetic methods applied to leukapheresis products from healthy donors. We also wanted to determine the kinetics of engraftment and incidence and severity of graft-versus-host disease (GVHD) after allogeneic transplantation of selected CD34 + cells. HLA-identical sibling donors received G-CSF. After leukapheresis, peripheral blood progenitor cells were selected using immunoadsorption (Ceprate SC) (n = 38) or immunomagnetic (Isolex 300) (n = 24) methods. Sixty-two patients, with a median age of 42 years (range 17-60) diagnosed with hematological malignancies were conditioned with either cyclophosphamide and total body irradiation (n = 43) or busulphan and cyclophosphamide (n = 19). GVHD prophylaxis consisted of cyclosporin A (CsA) and prednisone (n = 48), CsA alone (n = 11) and CsA and methotrexate (n = 3). The median yield and purity of CD34 + cells after the procedure was 65 and 66% with immunoadsorption, and 48 and 86% with immunomagnetic method, respectively. The median number (range) of CD34 + cells infused into the patients was 3.5 ؋ 10 6 /kg (1-9.6). The median number (range) of CD3 + cells administered was 0.4 ؋ 10 6 /kg (0.01-2) using immunoadsorption and 0.14 ؋ 10 6 /kg (0.03-2.5) using immunomagnetic methods. Neutrophil recovery Ͼ500 and Ͼ1000/ l was achieved at a median (range) of 13 days (8-22) and 14 days (9-31), respectively. Platelets recovered to Ͼ20 000 and Ͼ50 000/ l at a median (range) of 13 days (0-128) and 18 days (0-180), respectively. Two patients developed graft failure. Acute GVHD in patients at risk was clinical grade 0 (n = 43), I (n = 8), II (n = 4) and III (n = 1). No patient developed acute GVHD grade IV. Chronic GVHD was limited in two cases and extensive in four cases. The actuarial probability of acute GVHD II-IV was 10% (95% CI, 1-19%), and of extensive chronic GVHD was 12% (95% CI, 11-13%). The cumulative incidence of transplantrelated mortality was 12.6%, and this figure was 9% at 6 months. In conclusion, with the immunomagnetic procedure, a lower recovery and higher purity of CD34 + cells, and stronger TCD is obtained as compared to immunoadsorption (P = 0.008, P Ͻ 0.0001 and P = 0.0002, respectively). Our results also indicate that allogeneic transplantation of selected CD34 + cells is associated with a very rapid engraftment and with a low incidence of severe GVHD.