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Presence of the ficolin-2 Ala258Ser polymorphism in the donor independently predicts improved graft outcome. Based on mechanistic data, we propose that this functional polymorphism leads to more efficient handling of injured cells by phagocytozing cells, resulting in decreased intragraft exposure to danger signals and dampened alloimmune responses.

We read with interest the reviews by Ghouri et al. 1 and Martinez et al. 2 Ghouri et al. analyzed the association of nonalcoholic fatty liver disease (NAFLD) with cardiovascular disease (CVD) and concluded that although a diagnosis of NAFLD should prompt diabetes screening, it is insufficient for considering patients to be at high risk for CVD. Martinez et al. evaluated noninvasive methods for assessing liver fibrosis and recommended that those tests with the highest diagnostic accuracy be validated against liver biopsy to facilitate their implementation in clinical practice.We meta-analyzed prospective data regarding the natural history of NAFLD and studies assessing the diagnostic accuracy of noninvasive methods for liver disease severity against liver biopsy in NAFLD, and we reached the following conclusions 3 :1. The two NAFLD histological subtypes, simple steatosis (SS) and nonalcoholic steatohepatitis (NASH), have different risks of liver-related complications: SS progresses to cirrhosis in less than 5% of cases; NASH progresses to cirrhosis in 10% to 15% of cases over 10 years and in 25% to 30% of cases in the presence of advanced fibrosis. 2. NAFLD patients have a 1.44-to 2.05-fold higher rate of CVD (depending on whether the diagnosis is based on an aminotransferase elevation or radiological/histological criteria) than the general population; restricting the analysis to studies adjusting for metabolic syndrome did not change the risk. Importantly, CVD mortality did not differ among NAFLD histological subtypes. ; restricting the analysis to studies adjusting for metabolic syndrome did not change the risk. Whether the risk of diabetes differs among NAFLD histological subtypes remains unclear: in a communitybased study, the 13-year incidence of diabetes was 2.98-fold higher in NASH patients versus SS patients. 3According to our analysis, a diagnosis of NAFLD should prompt a thorough three-focus assessment of cardiovascular, metabolic, and liver-related risks (Table 1). 4 Liver-related risk assessment remains problematic because it requires liver histology. Three noninvasive methods have been extensively validated: enzyme-linked immunosorbent assay-detected cytokeratin 18 fragments (9 studies enrolling 856 participants) for the detection of NASH and the NAFLD fibrosis score (13 studies enrolling 3064 participants) and FibroScan (6 studies enrolling 563 participants) for the detection of advanced fibrosis. We believe that these methods should be promptly implemented in diagnostic algorithms to select patients for liver biopsy in routine clinical practice while we continue to search for the ideal noninvasive marker.

In contrast to their effect in the general population, 50 common genetic variations in innate immunity receptors do not influence susceptibility to bacterial/fungal infections after LT. In addition, no reproducible associations with acute rejection after LT were observed. Likely, transplant-related factors play a superior role as risk factors for bacterial/fungal infections and acute rejection after LT.

We carried out a multicenter performance evaluation of three new DNA-based human leukocyte antigen (HLA) typing assays: INNO-LiPA HLA-A Update, INNO-LiPA HLA-B Update, and INNO-LiPA HLA-DQB1 Update. After optimization, the accuracy rates were all 100%, and the final observed resolutions were 99.4, 92.4, and 85.6%, respectively. These rapid and easy-to-perform assays yielded results fully concordant with other DNA-based tissue typing tests.In order to optimize the selection of compatible organ and stem cell donors, DNA-based human leukocyte antigen (HLA) typing assays must not only be accurate but also take into account the continuing discovery of new HLA alleles (2). We recently updated three such HLA tests and then validated the new tests in two phases. First, we performed in-house assessments of the robustness of amplification and of the new probes by using well-characterized samples. In a second phase, reported below, we carried out external performance evaluations of the new assays.The three upgraded tests, INNO-LiPA HLA-A Update, INNO-LiPA HLA-B Update, and INNO-LiPA HLA-DQB1

Microdeletions, either subtelomeric or interstitial, are responsible for the mental handicap in approximately 10-20% of all patients. Currently, Multiplex Ligation-dependent Probe Amplification (MLPA) is widely used to detect these small aberrations in a routine fashion. Although cost-effective, the throughput is low and the degree of multiplexing is limited to maximally 40-50 probes. Therefore, we developed an array-based MLPA method, with probes identified by unique tag sequences, allowing the simultaneous analysis of 180 probes in a single experiment thereby covering all known mental retardation loci with at least two probes. We screened 120 patients with idiopathic mental retardation. In this group we detected 6 aberrations giving a detection rate of 5%, consistent with similar studies. In addition we tested 293 patients with mental retardation who were negative for fragile X syndrome and commercially available subtelomeric MLPA. We found seven causative rearrangements in this group (detection rate of 2.4%) thereby illustrating the value of including probes for interstitial microdeletion syndromes and additional probes in the telomeric regions in targeted screening sets for mental retardation. Array-based MLPA may thus be a good candidate to develop probe sets that rapidly detect copy number changes of disease associated loci in the human genome. This method may become a valuable tool in a routine diagnostic setting as it is a fast, user-friendly and relatively low-cost technique providing straightforward results requiring only 125 ng of genomic DNA.

Tricho-rhino-phalangeal (TRP) syndromes type I and II are caused by a defective gene located on chromosome 8q24.1. We report a family with 2 sibs affected with TRP type I in combination with an apparently balanced chromosome (8;18) translocation involving 8q24.11. It is very likely that the 8q24 translocation breakpoint is physically linked to the TRP gene(s), thereby facilitating future efforts to clone the TRP gene(s).