Prognostic value of blood group specificity and IL-28в genotype for the assessment of liver fibrosis in patients with chronic genotype 1 hepatitis C, non-responders to the treatment with pegylated interferon α-2 and ribavarin

Aim. To evaluate the prognostic value of blood group and IL-28B genotype with respect to dynamics of liver fibrosis (LF) in patients with chronic genotype-1 hepatitis C (HCV-1) who did not respond to antiviral therapy (AVT) with pegylated interferon alpha 2 (peg-IFN-α-2) and ribavarin (RBV) Material and methods. The study included 122 primary patients with HCV-1 who underwent paired liver biopsy or elastometry steam. The main group (n=66) consisted of patients who received AVT (peg-IFN-α-2/RBV) but failed to achieve a sustainable virologic response (SVR). Control group (n=56) comprised patients treated without AVT. Results. Negative dynamics of LF in patients of the main group occurred significantly more frequently than in the placebo group (p=0.025, φ2 criterion). LF dynamic patterns in patients of the main group varied depending on the IL-28B genotype and blood group, p=0.001 and p=0.014 respectively. Factorial analysis of negative LP dynamics in the main group revealed the relationship between blood group (fr=0,931) and IL-28B genotype (fr= 0.960) while classification analysis demonstrated the predictive value of combination of gene IL-28B polymorphism and blood group (p<0.0001). The assessment of probability of negative LF dynamics in the main group (logistic analysis) showed that IL-28B gene genotypes ST/TG, TT/TT,TG,GG and blood group A(II) alone or their combination increase the odds ratio of LF negative dynamics in SVR(-) under conditions of interferon therapy. In patients having blood group 0(I) and combination of gene IL-28B genotypes CC/TT, CT/TT with blood group A(II) the odds ratio of negative dynamics in SVR(-) is reduced under the same conditions. Conclusions. Blood group and IL-28B genotype predict dynamics of liver fibrosis in patients with HCV-1 not responding to interferon therapy.

Are erectile functions affected by AB0 blood group?

Aim: The aim of this study was to investigate whether there is a relationship between erectile dysfunction (ED), thought to be a vascular disease, and AB0 blood group. Material and Method: The study included 350 people abiding by the study criteria who applied to our clinic from April 2012-April 2015. The patients were divided into two groups including those with ED (Group 1) and those without (Group 2). Age, blood group, IIEF-5 score and presence of additional diseases were recorded. Erectile functions were analyzed according to blood group. Results: There was no difference between the mean age of 111 patients with ED and that of 239 patients without ED included in the study (p = 0.284). There was no difference between patients in the two groups in terms of smoking, alcohol use, hypertension and diabetes (p &gt; 0.05). Among patients in the ED group, the mean IIEF-5 score according to blood group was 19.8 ± 5.04 in the 0 blood group, 16.5 ± 5.2 in the A blood group, 17.2 ± 5.3 in the B blood group and 13.3 ± 3.02 in the AB blood group. The IIEF-5 scores of individuals in the 0 blood group were significantly high compared to individuals in other blood groups (p = 0.004). Logistic regression analysis found that compared to the 0 blood group, the erectile dysfunction risk was 3.9 times greater for the A blood group, 3.5 times greater for the B blood group and 4.7 times greater for the AB blood group (p = 0.001) (Table 3). Conclusion: The risk of erectile dysfunction was significantly increased for individuals in the A, B and AB blood groups compared to individuals in the 0 blood group.

Complex Relationship of Blood Group H, ABO Glycans, and Von Willebrand Factor Levels

Background: ABO(H) is a carbohydrate blood group system expressed in multiple tissues including red blood cells, blood vessels, and mucosal surfaces. ABO is the largest known genetic modifier of plasma VWF level (VWF:Ag). It has been hypothesized that the effect of ABO on VWF is mediated by H glycan density. FUT2, the gene underlying Secretor phenotype, encodes a glycosyltransferase synthesizing H antigen in mucosal tissues, and variation in the gene has also previously been associated with VWF:Ag, but past studies have been conflicting. To clarify these relationships, we studied the relationship between VWF:Ag, ABH glycans, and FUT2 genotype. Methods: The primary study group was a representative cohort of US blood donors from the Retrovirus Epidemiology Donor Study (REDS, N=499). A validation cohort of unrelated individuals was created from the Genes and Blood Clotting Study (GABC), healthy siblings between ages 14 and 35 years from University of Michigan, Ann Arbor, by choosing a random individual from each family (N=488). VWF:Ag was determined by ELISA in platelet poor plasma. Forensic techniques were adapted to detect ABH glycans in whole blood (REDS) or RBC-rich, frozen buffy coat (GABC). A and B glycans were detected using anti-A or anti-B (Immucor). A biotinylated Ulex europaeus agglutinin (UEA lectin, Vector Labs) was used to detect H. Relative A, B, and H antigen density was quantified on dot blots with ImageQuant (GE). In REDS, functional FUT2 alleles (Secretor) were determined by Sanger sequencing of FUT2 exon 2. FUT2 copy-number was assayed with real-time quantitative PCR. In GABC, FUT2 genotypes were determined through SNP genotyping (Illumina). In REDS, genotype data was phased (BEAGLE) to identify functional haplotypes. In GABC, functional alleles were inferred from the genotypes of two SNPs (rs601338, rs1047781) that determined secretor status in nearly all samples in REDS (see below). Multivariate regression was applied to VWF:Ag as a function H antigen density and O vs. non-O blood group, both separately and within the same model. All models were adjusted for age, gender, and self-reported ethnicity. Results: ABO blood group frequencies in both cohorts were similar to that of the US population. VWF:Ag differed significantly between ABO blood groups with lower values in blood group O versus non-O (REDS: ratio = 0.75, 95% CI [0.71, 0.80], p<2.2e-16, log-linear regression). H glycan density also differed between ABO blood group (p<2.2e-16, Kruskal-Wallis; O vs. non-O, ratio = 2.03, 95% CI [1.88, 2.19], p<2.2e-16). A significant fraction of H glycan density variation was attributable to ABO (REDS r2 =0.45; GABC r2 =0.34), but a wide range of H glycan density was observed in all blood groups, including within blood group O. In multivariate regression, both H glycan density and O versus non-O blood group, considered separately or in the same model, were significantly associated with VWF:Ag (REDS combined model: p = 2.9e-5 and 2.7e-4 for H glycan and blood group, respectively). In GABC but not in REDS, regression was also significant for an interaction between H glycan density and blood group (p = 0.031). Both cohorts estimated a stronger association of VWF:Ag with H in non-O blood groups. FUT2 sequencing in the REDS cohort identified 22 distinct FUT2 haplotypes. 99.5% (497/499) of individuals could be accurately assigned FUT2 genotypes based on the common W154* (rs601338) polymorphism alone. In GABC, this decreased to 94% (476/488) due to higher frequency of a hypomorphic allele (rs1047781) more commonly found in Asian individuals. In REDS, quantitative PCR did not identify copy-number variation at FUT2. There was no significant association between FUT2 genotype-predicted function and VWF:Ag or H glycan density in either cohort. Conclusion: H glycan density correlated with VWF:Ag in both cohorts. H glycan density could mediate the association between ABO blood group and VWF:Ag. If so, this suggests a non-linear, complex relationship between H and VWF and a separate ABO mechanism cannot be excluded. In both cohorts, there was no association of FUT2 (Secretor) genotype with VWF. Our data suggest prior focused approaches to FUT2 genotyping are at risk to undercall non-functional alleles, particularly in cohorts with non-European ancestries. Taken together, these indicate blood group H may be a significant modifier of VWF:Ag, and that this effect is not due to the influence of Secretor phenotype. Disclosures Johnsen: Octapharma: Other: Speaker; Biogen: Research Funding; CSL Behring: Other: Speaker.

The human Pk histo-blood group antigen provides protection against HIV-1 infection

Several human histo-blood groups are glycosphingolipids, including P/P1/Pk. Glycosphingolipids are implicated in HIV-host-cell-fusion and some bind to HIV-gp120 in vitro. Based on our previous studies on Fabry disease, where Pk accumulates and reduces infection, and a soluble Pk analog that inhibits infection, we investigated cell surface–expressed Pk in HIV infection. HIV-1 infection of peripheral blood–derived mononuclear cells (PBMCs) from otherwise healthy persons, with blood group P1k, where Pk is overexpressed, or blood group p, that completely lacks Pk, were compared with draw date–matched controls. Fluorescence-activated cell sorter analysis and/or thin layer chromatography were used to verify Pk levels. P1k PBMCs were highly resistant to R5 and X4 HIV-1 infection. In contrast, p PBMCs showed 10- to 1000-fold increased susceptibility to HIV-1 infection. Surface and total cell expression of Pk, but not CD4 or chemokine coreceptor expression, correlated with infection. Pk liposome–fused cells and CD4+ HeLa cells manipulated to express high or low Pk levels confirmed a protective effect of Pk. We conclude that Pk expression strongly influences susceptibility to HIV-1 infection, which implicates Pk as a new endogenous cell-surface factor that may provide protection against HIV-1 infection.

The Half-life of Infused Factor VIII Is Shorter in Hemophiliac Patients with Blood Group 0 than in those with Blood Group A

SummaryA considerable inter-individual variation in half-life of infused factor VIII is observed among patients with hemophilia A. The factors contributing to this wide range in factor VIII half-life are not known in detail. We analysed the pharmacokinetics of infused factor VIII in 32 patients with hemophilia A, comprising 20 brothers from 10 families, 3 and 4 brothers from 2 families, and 5 patients from 5 single families, respectively. Multiple linear regression analysis was used to asses the effect of several variables on factor VIII half-life. We found that the pre-infusion von Willebrand factor antigen levels (vWF:Ag) were positively correlated with factor VIII half-life (r = 0.52, p = 0.002), i. e., each variable was associated with about 27% of the variance of the other. In fraternal pairs, familial clustering was significant for AB0 blood group (p < 0.001), but could not be detected for factor VIII half-lives or pre-infusion vWF:Ag levels. vWF:Ag level (p = 0.001) and AB0 blood group (p = 0.003) significantly determined factor VIII half-life, whereas age, length, bodyweight, the presence or absence of a factor VIII gene inversion, and Rhesus phenotype did not. Patients with blood group 0 exhibited a statistically significant shorter factor VIII half-life than patients with blood group A (15.3 versus 19.7 h, respectively) (p = 0.003). Patients with blood group A and 0 differ in respect to the presence of anti-A antibodies in the latter. It is possible that these anti-A antibodies interact with endogenous vWF, thus affecting the half-life time of the factor VIII/vWF complex.