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International audience; Lipoprotein(a) [Lp(a)] was identified in 1963 in human serum as an LDL-like particle and is today recognized as an important risk factor for cardiovascular diseases (Ref: Nordestgaard and col. Lipoprotein(a) as a Cardiovascular Risk Factor: Current Status. Eur Heart J 2010; 31, 2844-53). The LDL-like core of Lp(a) is covalently bound to a unique plasminogen-related glycoprotein, called apolipoprotein(a) [apo(a)]. This protein is highly polymorphic between individuals due to a specific domain namely Kringle IV type2 (KIV-2), which can be present as tandemly repeated from 3 to >40 times. Apo(a) seems to be also responsible of many of the pro-atherogenic and pro-trombotic properties of Lp(a). For example, smaller apo(a) isoforms (i.e. Lp(a) isoforms with a low number of KIV-2 copies) correlate with higher cardiovascular risk (Ref: Gazzaruso C, et al. Association of lipoprotein(a) levels and apolipoprotein(a) phenotypes with coronary heart disease in patients with essential hypertension. J Hypertens 1997;15(3):227-35). However, the molecular basis underlying the different atherogenic potential has not been fully understood. Biophysical characterization of different Lp(a) isoforms may offer insights into the role of apo(a) size in atherosclerotic diseases. In this work, we present interfacial measurements of four purified Lp(a) isoforms containing 20, 24, 25 and 29 KIV-2 domains (K20, K24, K25, and K29).

BACKGROUND: Nucleic acid testing (NAT) for hepatitis C virus (HCV) and human immunodeficiency virus (HIV) has been implemented in several European countries and in the United States, while hepatitis B virus (HBV) NAT is still being questioned by opinions both in favor and against such an option, depending on the HBV endemicity, health care resources, and expected benefits. STUDY DESIGN AND METHODS: This survey was aimed to assess the NAT impact in improving the safety of blood supply in Italy, 6 years after implementation. The study involved 93 Italian transfusion centers and was carried out in 2001 through 2006. A total of 10,776,288 units were tested for the presence of HCV RNA, 7,932,430 for HIV RNA, and 3,405,497 for HBV DNA, respectively. RESULTS: Twenty-seven donations or 2.5 per million tested were HCV RNA–positive/anti-HCV–negative; 14 or 1.8 per million units tested were HIV RNA–positive/anti-HIV–negative; and 197 or 57.8 per million donations tested were HBV DNA–positive/hepatitis B surface antigen–negative. Of the latter, 8 (2.3/106) were collected from donors in the window phase of infection and 189 (55.5/106) from donors with occult HBV. Sixty-eight percent of the latter donors had hepatitis B surface antibody, 74.5 percent of whom with concentrations considered protective (≥10 mIU/mL). CONCLUSION: NAT implementation has improved blood safety by reducing the risk of entering 2.5 HCV and 1.8 HIV infectious units per million donations into the blood supply. The yield of NAT in detecting infectious blood before transfusion was higher for HBV than for HCV or HIV. However, the benefit of HBV NAT in terms of avoided HBV-related morbidity and mortality in blood recipients needs to be further evaluated.

The importance of donor-recipient human leukocyte antigen (HLA)-DPB1 matching for the clinical outcome of unrelated hematopoietic stem cell transplantation (HSCT) is controversial. We have previously described an algorithm for nonpermissive HLA-DPB1 disparities involving HLA-DPB1*0901,*1001,*1701,*0301,*1401,*4501, based on T-cell alloreactivity patterns. By revisiting the immunogenicity of HLA-DPB1*02, a modified algorithm was developed and retrospectively tested in 621 unrelated HSCTs facilitated through the Italian Registry for onco-hematologic adult patients. The modified algorithm proved to be markedly more predictive of outcome than the original one, with significantly higher KaplanMeier probabilities of 2-year survival in permissive compared with nonpermissive transplantations (55% vs 39%, P = .005). This was the result of increased adjusted hazards of nonrelapse mortality (hazard ratio [HR] = 1.74; confidence interval [CI], 1.19-2.53; P = .004) but not of relapse (HR = 1.02; CI, 0.73-1.42; P = .92). The increase in the hazards of overall mortality by nonpermissive HLA-DPB1 disparity was similar in 10 of 10 (HR = 2.12; CI, 1.23-3.64; P = .006) and 9 of 10 allele-matched transplantations (HR = 2.21; CI, 1.28-3.80; P = .004), both in early-stage and in advanced-stage disease. These data call for revisiting current HLA matching strategies for unrelated HSCT, suggesting that searches should be directed up-front toward identification of HLA-DPB1 permissive, 10 of 10 or 9 of 10 matched donors. (Blood. 2009; 114:1437-1444) RI Porfirio, Berardino/I-1988-2012

Extracorporeal photochemotherapy (ECP) is a therapeutic approach based on the biological effects of ultraviolet light (UV) - A and psoralens on mononuclear cells collected by apheresis. Recently, ECP has been under investigation as an alternative treatment for various immune and autoimmune diseases. The aim of this study was to evaluate the safety and feasibility of a new three-step ECP technique, in terms of reproducibility, acceptance, tolerability, and short and long term side effects.Seventeen patients affected by acute or chronic graft-versus-host disease (GvHD), pemphigus vulgaris, or interferon-resistant chronic hepatitis C and one patient being treated for prevention of heart transplant rejection underwent 240 ECP procedures. MNC collection and processing parameters were recorded, biological effects of UV-A/8 methoxy-psoralen (8-MOP) were evaluated, and short and long term side effects were monitored.At a mean follow up of 7 months (range 2-19) 240 ECP had been completed, a mean of 7,136 mL (range 1,998-10,591) of whole blood having beenprocessed per procedure. The mean of total nucleated cells collected per procedure was 6.5x109 (range 0.65-23.8), with a mean MNC percentage of 85% (41. 4-98%) in a mean final volume of 115.5 mL (37-160). No severe side effects were documented and no infectious episodes occurred throughout the course of the treatment.The new ECP technique was highly reproducible as regards the collection and each processing step. Short and long term side effects were mild. No increase in infectious episodes was recorded. All patients willingly underwent ECP, demonstrating an excellent tolerability for the procedure even after several courses.