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Introduction Our goal was to study whether influenza vaccination induced antibody mediated rejection in a large cohort of solid organ transplant recipients (SOTR). Methods Serum anti-Human Leukocyte Antigen (HLA) antibodies were determined using class I and class II antibody-coated latex beads (FlowPRA TM Screening Test) by flow cytometry. Anti-HLA antibody specificity was determined using the single-antigen bead flow cytometry (SAFC) assay and assignation of donor specific antibodies (DSA) was performed by virtual-crossmatch. Results We studied a cohort of 490 SOTR that received an influenza vaccination from 2009 to 2013: 110 (22.4%) received the pandemic adjuvanted vaccine, 59 (12%) within the first 6 months post-transplantation, 185 (37.7%) more than 6 months after transplantation and 136 (27.7%) received two vaccination doses. Overall, no differences of anti-HLA antibodies were found after immunization in patients that received the adjuvanted vaccine, within the first 6 months post-transplantation, or based on the type of organ transplanted. However, the second immunization dose increased the percentage of patients positive for anti-HLA class I significantly compared with patients with one dose (14.6% vs. 3.8%; P = 0.003). Patients with pre-existing antibodies before vaccination (15.7% for anti-HLA class I and 15.9% for class II) did not increase reactivity after immunization. A group of 75 (14.4%) patients developed de novo anti-HLA antibodies, however, only 5 (1.02%) of them were DSA, and none experienced allograft rejection. Only two (0.4%) patients were diagnosed with graft rejection with favorable outcomes and neither of them developed DSA. Conclusion Our results suggest that influenza vaccination is not associated with graft rejection in this cohort of SOTR.

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Ursodeoxycholic acid (UDCA) induces bicarbonate-rich hypercholeresis by incompletely defined mechanisms that involve the stimulation of adenosine triphosphate (ATP) release from cholangiocytes. As nitric oxide (NO) at a low concentration can stimulate a variety of secretory processes, we investigated whether this mediator could be implicated in the choleretic response to UDCA. Our in vivo experiments with the in situ perfused rat liver model in anesthetized rats, showed that UDCA infusion increased the biliary secretion of NO derivatives, hepatic inducible NO synthase expression, and NO synthase activity in liver tissue. UDCA also stimulated NO release by isolated rat hepatocytes. In contrast to UDCA, cholic acid was a poor inducer of NO secretion, and tauroursodeoxycholic acid showed no effect on NO secretion. Upon UDCA administration, NO was found in bile as low-molecular-weight nitrosothiols, of which S-nitrosoglutathione (GSNO) was the predominant species. UDCA-stimulated biliary NO secretion was abolished by the inhibition of inducible NO synthase with N x -nitro-L-arginine methyl ester in isolated perfused livers and also in rats whose livers were depleted of glutathione with buthionine sulfoximine. Moreover, the biliary secretion of NO species was significantly diminished in UDCAinfused transport mutant [ATP-binding cassette C2 (ABCC2)/multidrug resistance-associated protein 2 (Mrp2)-deficient] rats, and this finding was consistent with the involvement of the glutathione carrier ABCC2/Mrp2 in the canalicular transport of GSNO. It was particularly noteworthy that in cultured normal rat cholangiocytes, GSNO activated protein kinase B, protected against apoptosis, and enhanced UDCA-induced ATP release to the medium; this effect was blocked by phosphoinositide 3-kinase inhibition. Finally, retrograde GSNO infusion into the common bile duct increased bile flow and biliary bicarbonate secretion. Conclusion: UDCA induces biliary secretion of GSNO, which contributes to stimulating ductal secretion. (HEPATOLOGY 2010;52:667-677) Abbreviations: ABC, adenosine triphosphate-binding cassette; AE2, anion exchanger 2; AKT, protein kinase B; ATP, adenosine triphosphate; BSO, buthionine sulfoximine; BV, beauvericin; BW, body weight; CA, cholic acid; GSNO, S-nitrosoglutathione; iNOS, inducible nitric oxide synthase; IPRL, isolated and perfused rat liver; isPRL, in situ perfused rat liver; L-NAME, N x -nitro-L-arginine methyl ester; LMw-SNO, low-molecular-weight nitrosothiol; LY294002, 2-morpholin-4-yl-8-phenylchromen-4-one; Mrp2, multidrug resistance-associated protein 2; MS, mass spectrometry; NO, nitric oxide; NOS, nitric oxide synthase; NRC, normal rat cholangiocyte; PI3K, phosphoinositide 3-kinase; SNO, nitrosothiol; TR À , transport mutant; TUDCA, tauroursodeoxycholic acid; UDCA, ursodeoxycholic acid;WT, wild type. From the

BackgroundMutations in the progesterone receptor (PR) gene, PROGINS, have been studied in relation to hepatitis E virus (HEV) infection. Patients with the PROGINS gene may develop a worse clinical course of hepatitis E. The aim of our study was to evaluate the influence of PROGINS on the susceptibility to and the clinical course of HEV infection in HIV patients.MethodsThis study included patients with HIV who were evaluated in previous prospective studies for the prevalence and incidence of HEV. The following three groups of patients were studied: (i) never infected, (ii) past infections, and (iii) recently infected. We determined the PR genotype to evaluate the proportion of patients who were homozygous for PROGINS according to HEV infection. We also compared the proportion of PROGINS carriers with a recent HEV infection according to their symptomatology.ResultsIn this study, 311 patients infected with HIV were included. Of those patients, 198 were homozygous wild type (63.7%), 91 were heterozygous (29.3%), and 22 were homozygous PROGINS (7.1%). We found that the homozygous PROGINS genotype in women was associated with a lower HEV seroprevalence. In addition, in patients with a recent HEV infection, none of those homozygous for PROGINS presented symptoms.ConclusionThe PROGINS mutation plays a protective role against HEV infection and is associated with subclinical infection in HIV-infected patients, particularly women.

BackgroundIdentifying pig farms infected with hepatitis E virus (HEV) is a key aspect to implement surveillance programmes for this emerging zoonotic agent. Detection of HEV in blood has several drawbacks, including animal handling, economic costs and animal stress. The objective of this study was to evaluate the effectiveness of a non-invasive screening approach for determining the HEV status of pig farms under different management systems.MethodsForty stool samples randomly collected from the pen floor of 17 intensive pig farms and the yard of nine extensive ones were tested for HEV RNA. The invasive method used to confirm the HEV status of the farm was HEV RNA analysis of serum samples randomly collected from 40 animals on each farm.ResultsTwenty-one HEV-positive farms were detected by invasive and non-invasive methods. No positive serum or stool samples were detected on five intensive farms. A high intertest agreement (K=1; P<0.00001) was observed between both methodologies, showing the stool screening approach a 100 per cent of sensitivity and specificity with respect to the invasive method. Likewise, a significant negative relationship was observed between the HEV within-farm prevalence and the number of the first HEV-positive stool sample found (Spearman’s rho=−0.64; P=0.0004). This negative relationship was higher in intensively managed farms.ConclusionThis non-invasive screening approach could be reliably applied in a large-scale surveillance programme for determining the HEV status of pig farms under different management systems.