Infectivity of hepatic allografts with antibodies to hepatitis B virus

BACKGROUND: Since suitable recipients for hepatic allografts from donors with antibodies to hepatitis B virus (HBV) have not been determined, a review of our 7-year experience with donors positive for hepatitis B surface antibody (anti-HBs), hepatitis B core antibody (anti-HBc), or both was undertaken. METHODS: Recipients of hepatic allografts from donors with antibodies to HBV were identified by a retrospective review of procurement records and screened for HBV infection. RESULTS: From January 1, 1990, to January 1, 1997, 2578 liver transplants were performed and 140 (5.4%) recipients received an allograft from a donor with antibodies to HBV. Twenty-five of 48 recipients of a hepatic allograft from a donor positive only for anti-HBs were screened and none developed HBV infection. Twenty-five of 41 naive recipients of a hepatic allograft from an anti-HBc positive donor were screened and 18/25 (72%) developed HBV infection. Four of these 18 naive recipients with HBV infection received an allograft from a donor positive for both anti-HBc and anti-HBs. Seven of 13 anti-HBs-positive recipients of an allograft from an anti-HBc-positive donor were screened and none developed HBV infection. Fifteen of 16 recipients positive only for anti-HBc who received a hepatic allograft from an anti-HBc-positive donor were screened and 2/15 (13%) developed HBV infection. CONCLUSIONS: Hepatic allografts from donors positive only for anti-HBs do not transmit HBV infection. Hepatic allografts from anti-HBc-positive donors frequently transmit HBV infection to naive recipients regardless of the donor anti-HBs status, and antiviral prophylaxis may be indicated. Anti-HBs-positive recipients appear resistant to HBV infection after orthotopic liver transplantation with an allograft from an anti-HBc-positive donor. Recipients positive only for anti-HBc infrequently develop HBV infection when transplanted with an allograft from an anti-HBc-positive donor; however, HBV prophylaxis may be justified.     

Opsonic effect of equine plasma from different donors

The ability of equine plasma from different donors to enhance phagocytic capacity was assessed in neutrophils obtained from seven foals, aged 7-8 days (Study A), and from seven adult horses (Study B). Neutrophils were allowed to phagocytize fluorescent yeast cells opsonized with plasma from one of three donors or with pooled serum, all previously frozen (-18 degrees C) and thawed. The results were analysed by flow cytometry. In study A, fresh autologous foal serum was also used for opsonization, and in study B, heat-inactivated plasma and pooled serum were used in addition to untreated samples. The plasma from donor GN induced a higher number of truly phagocytic neutrophils (mean 78%) than did plasma from donors GD (68%), OD (66%) and pooled serum (59%) when neutrophils from foals were used (p < 0.05). Similar results were obtained when adult neutrophils were used. Phagocytosis was markedly reduced with beat-inactivated plasma as a result of there being fewer phagocytic neutrophils and less phagocytized material per cell. The opsonic capacities of the autologous foal sera were lower than that of adult donor plasma in six out of seven foals. It is concluded that there is significant individual variation in the opsonic activity amongst plasma donors with similar serum IgG concentrations. The results were consistent irrespective of whether neutrophils from adults or foals were used.     

Berylliosis as an auto-immune disorder

Four random samples representing populations at low (volunteer blood donors), intermediate, (VD clinic patients), high (family contacts of chronic antigen carriers) and very high (male homosexuals) risk of exposure to HBV were surveyed. Among HBsAg and anti-HBs negative individuals an average of 3.3% were found to be anti-HBc positive, and among those with anti-HBs, 19.4% were anti-HBc positive. Anti-HBc, with concurrent anti-HBs and without, was detected more frequently in the high risk samples than in the low risk. Individuals was a past history of acute viral hepatitis were more frequently anti-HBc positive than those without such a history, and anti-HBc positivity was frequently accompanied by serum transaminase elevation. Anti-HBc may persist for many years after an episode of acute hepatitis. In households of carriers, the highest frequency of anti-HBc was observed among spouses, which would argue for the possibility of sexual transmission. A significant excess of females with both types of antibody was observed in families of carriers. Anti-HBc determinations in conjunction with other HBV markers, provide a useful new tool for epidemiologic studies.     

Evolutional neurologic evaluation of seven year-old children born prematurely

Personnel (1856 subjects) belonging to local health units (medical and paramedical staff) that have been vaccinated since 1984 against hepatitis B virus (HBV) with HBsAg plasma purified preparations (Hevac-B and H-B-Vax) or recombinant DNA preparation (Engerix-B) were followed in plasma anti-HBs antibody levels. At the end of the protocols, different seroconversion percentages and different anti-HBs levels were reached: the best results were obtained with Engerix-B. Sex and principally age influenced the antibody production: women generally reached highest protective antibody levels and the 21-30 year group was more responsive than other groups. The injection of a supplementary 4th or 5th dose in low or non-responders could restore the specific immunity in the majority of the subjects and increase the anti-HBs level. The time course after the immunization of antibody levels depended on the level reached at the end of vaccination schedule. These data suggest that different antibody level monitorings of vaccinated subjects, planned on the basis of the antibody level reached at the end of vaccination, could prevent a loss of protection against the HBV infection.     

Histologic transformation in follicular lymphoma

Blood donors (n = 663) from the Novy Jicín district, Czech Republic, were examined for the presence of antibodies to Toxoplasma gondii. The indirect fluorescent antibody test was used to simultaneously detect IgM and IgG antibodies. Titres > or =20 were considered positive. The seroprevalence of IgM and IgG antibodies was 2.4% and 32.1%, respectively. Periods, for how long the blood donors were infected, are discussed.     

Inhibition of protein S by autoantibodies in patients with acquired protein S deficiency

This study was undertaken to analyze antibodies to protein S (PS) in patients with an acquired PS deficiency. Plasma from symptomatic patients with acquired (n = 14) or congenital (n = 10) PS deficiency and 10 healthy donors was screened for PS antibodies by immunoblotting and for anti-phospholipid antibodies. PS antibodies (IgG) were detected in five of the patients with acquired PS deficiency. These antibodies belonged to the G1 and G4 immunoglobulin subclasses. IgG fractions from the same 5 patients were shown to inhibit PS activity. The inhibition of PS activity by the 5 IgG fractions was shown to be time- and dose-dependent and was abolished following incubation with purified PS, while no effect was found after absorption with cardiolipin micelles. In addition, anticardiolipin monoclonal or human purified antibodies, failed to exert significant PS inhibition. These findings demonstrate that anti-PS antibodies are able to inhibit PS activity and that this is independent of anti-phospholipid antibodies. Given the clinical features of the patients, these antibodies should be regarded as an expression of the broad autoimmune syndrome involving the phospholipid-binding plasma proteins.     

Response of colony stimulating factor in cancer chemotherapy induced myelosuppression--a case report

BACKGROUND: The aim of the study was to describe the seroprevalence against Parvovirus B19 in a random sample of blood donors in the Hospital Universitario de Salamanca. METHODS: We studied the presence of IgG and IgM antibodies against Parvovirus B19 in 136 sera from asymptomatic blood donors by enzyme immunoassay methods. RESULTS: From 136 samples tested, 88 (64.7%) had positive absorbance values for IgG. Forty eight samples (35.5%) were negative. IgM was negative in all cases. We did not find indeterminate results. DISCUSSION: Parvovirus primoinfection usually happens in the childhood. Thus, we can expect a high percentage of general population to have antibodies against Parvovirus B19. Anti-Parvovirus B19 antibodies prevalence in blood donors was 64.7%. This failure is similar to data reported before (65%). Clinical importance of these viruses in currently related with hemathopoyesis diseases and with the possible role in theratogenesis. The presence of IgG seems to give protection except in some chronic infections recently described.     

Evaluation of commercial slides for detection of immunoglobulin G against Bartonella henselae by indirect immunofluorescence

Four commercial slides were compared with in-house slides for the detection of immunoglobulin G (IgG) against Bartonella henselae in 58 healthy persons from a rural region by an indirect immunofluorescence assay. MRL-BA slides (MRL Diagnostics, USA) and Virion slides (Virion, Switzerland) with agar-derived Bartonella henselae showed IgG titers of > or = 1:256 in 44.8% and 51.7%, respectively, whereas Bion slides (Bios, Germany), MRL-Vero slides (MRL Diagnostics), and in-house slides with cell-associated Bartonella henselae showed such titers in 3.4%, 5.1% and 3.4%, respectively. The MRL-Vero slides (Bartonella IgG substrate slides, MRL Diagnostics) were further evaluated with 26 patients with cat scratch disease, 20 patients with lymphadenopathy not due to cat scratch disease, 100 blood donors from an urban area, and 120 blood donors from a mixed urban/rural area. In our mixed urban/rural population the IgG titer of 1:256 had a sensitivity of 84.6% and a specificity of 93.4% for the serodiagnosis of cat scratch disease. Seroprevalence was higher in blood donors from the mixed area (50.8%) than from the urban area (37%). MRL-Vero slides were considered useful for the serodiagnosis of cat scratch disease by indirect immunofluorescence and have replaced our in-house system. However, patients with low IgG titers should be retested three to four weeks after initial sampling to demonstrate a possible rise of IgG titers in paired sera.     

Aerobic and anaerobic bacterial flora in chronic sinusitis in adults

Although autoantibodies to interleukin-1 alpha (IL-1 alpha autoantibodies) are known to be present in sera of apparently healthy humans, their frequency of occurrence and significance are unclear. To determine the prevalence of detectable IL-1 alpha autoantibodies in normal human blood, we screened the plasma of blood donors (6290 subjects: 3977 men and 2313 women, ages 16 to 64 yr) by a radioimmununoassay which we developed using a method that could detect over 5 ng/ml. Moreover, we investigated immunoglobulin class of IL-1 alpha autoantibodies and also their function. IL-1 alpha autoantibodies were detected in 14.6% of the 6290 donors. Their frequency was higher in males than females (16.6% vs. 11.2%, p < 0.01) and increased with age in both sexes. The proportion of subjects with a high IL-1 alpha autoantibodies titers also increased with age. We showed that IL-1 alpha autoantibodies were of the IgG class and that they had neutralizing function to IL-1 alpha by receptor assay. Neutralizing activity was only shown in plasma with concentration of IL-1 alpha autoantibodies, the level of which was over 1000 ng/ml. The affinity of the IL-1 alpha autoantibodies in plasma was between 2.1 x 10(-10) and 1.2 x 10(-9) M (mean 6.4 x 10(-10)M). Our results provide a basis for comparison with IL-1 alpha autoantibodies prevalence between healthy states and disease states, and suggest that IL-1 alpha autoantibodies may play a significant role in modulating the effects of excessive IL-1 alpha at local site or in systemic regions.     

Induction of antigen-specific isotype switching by in vitro immunization of human naive B lymphocytes

The use of in vitro immunization technology for the generation of human antigen-specific antibodies has essentially resulted in low affinity IgM antibodies, resembling an in vivo primary immune response. We now describe a detailed reproducible protocol for a two-step in vitro immunization, which yields isotype switched, antigen-specific human antibodies. The immunizing antigen was a 30aa synthetic peptide, containing both a B (15aa V3 peptide of the HIV-1) and a T helper cell epitope (15aa peptide from tetanus toxin). The immunization protocol includes: (i) a selection procedure of donors with a memory T cell response against tetanus toxoid; (ii) immunization of mature naive peripheral B lymphocytes in two distinct phases, involving a primary and a secondary step. None of the donors which were examined after primary immunization showed at any time an IgG anti-V3 specific antibody response, while all the donors showed an IgM response. After the secondary immunization step, anti-V3 antibodies of both IgM and IgG isotypes were detected. The switch frequency event was high among the tested donors (5/8).     

Peptides derived from collagen: new biochemical markers of bone metabolism]

OBJECTIVE: To study a possible association of the Helicobacter pylori seroprevalence with ABO(H) and Lewis (a,b) blood group phenotypes in blood donors. DESIGN: A cross-sectional study of blood donors using ABO(H) and Lewis (a,b) blood group phenotype as predictors. METHODS: ABO(H) and Lewis (a,b) blood group phenotyping was performed with monoclonal antibody. The H. pylori immunoglobulin G (IgG) antibody relative activity was evaluated by enzyme-linked immunosorbent assay (ELISA) using acid glycine extract from H. pylori. SUBJECTS: One hundred and fifty-nine randomly selected blood transfusion donors. RESULTS: The individuals with Lewis (a+b-)/non-secretor phenotype showed a significantly higher proportion of the H. pylori-seronegative subjects and a lower IgG immune response to H. pylori antigens as compared with the individuals of Lewis (a-b+)/secretor phenotype. CONCLUSION: The Lewis (a,b) histo-blood group antigens are implicated in the mechanisms of naturally occurring resistance to H. pylori infection.     

High prevalence of Helicobacter pylori in liver cirrhosis: relationship with clinical and endoscopic features and the risk of peptic ulcer

In 153 consecutive patients with cirrhosis we assessed: (1) the prevalence of IgG to Helicobacter pylori and compared it with that found in 1010 blood donors resident in the same area; and (2) the relationships of IgG to Helicobacter pylori with clinical and endoscopic features and with the risk of peptic ulcer. The IgG to Helicobacter pylori prevalence of cirrhotics was significantly higher than in blood donors (76.5% vs 41.8%; P < 0.0005) and was not associated with sex, cirrhosis etiology, Child class, gammaglobulins and hypertensive gastropathy. In both groups, the prevalence of IgG to Helicobacter pylori was significantly higher in subjects over 40. Among patients with cirrhosis a significantly higher prevalence of Helicobacter pylori was found in patients with previous hospital admission (P = 0.02) and/or upper gastrointestinal endoscopy (P = 0.01) and patients with peptic ulcer (P = 0.0004). Multivariate analysis identified increasing age and male sex as risk factors for a positive Helicobacter pylori serology and no independent risk factors for peptic ulcer. The high prevalence of Helicobacter pylori-positive serology found in the present series is related to age and sex and might also be explained by previous hospital admissions and/or upper gastrointestinal endoscopy. Our results do not confirm the role of Helicobacter pylori as risk factor for peptic ulcer in patients with liver cirrhosis.     

Effects of gamma irradiation on red cells from donors with sickle cell trait

BACKGROUND: Transfusion-associated graft-versus-host disease can be prevented by gamma irradiation of blood components. Red cells (RBCs) from sickle cell disease patients may exhibit oxidative changes of RBC membranes due to the instability of hemoglobin (Hb) S. Persons with sickle cell trait are eligible to donate blood, and 35 to 45 percent of their total Hb is Hb S. The effect of gamma irradiation on RBCs from such persons is of interest. STUDY DESIGN AND METHODS: RBCs from 12 donors with sickle cell trait (Hb AS) and from 12 with normal Hb (Hb AA) were studied. Each of the 24 RBC units was divided equally into two transfer bags via a sterile connecting device. One bag from each RBC unit received a 2500-cGy dose of gamma irradiation at its mid-plane and was stored at 4 degrees C; the second set of bags was stored without irradiation. For RBCs from 6 donors with Hb AS and 6 donors with Hb AA, units were irradiated on Day 7 and studied on Day 35 of storage (Group 1). For the RBCs from the other 6 donors with Hb AS and the other 6 donors with Hb AA, units were irradiated on Day 28 and studied on Day 42 of storage (Group 2). RESULTS: For Group 1 and Group 2, plasma potassium and plasma Hb concentrations were significantly higher and RBC ATP concentrations were slightly lower in the irradiated units than in the nonirradiated units. In Group 1 and Group 2, there were no significant differences in the plasma potassium or RBC ATP concentrations in either the irradiated or the nonirradiated units of RBCs from donors with Hb AS and donors with Hb AA. Plasma Hb concentrations were consistently lower in the units from donors with Hb AS, whether or not they were irradiated. However, in both groups, proportionally similar changes in plasma Hb concentration were detected when the irradiated Hb AS and Hb AA units were compared to nonirradiated Hb AS and Hb AA units. CONCLUSION: Gamma irradiation of RBCs from donors with Hb AS or with Hb AA resulted in comparable changes in plasma potassium, RBC ATP, and plasma Hb concentrations, although donors with Hb AS had lower plasma Hb. RBCs from donors with Hb AS subjected to 2500 cGy of gamma irradiation did not evidence a storage lesion greater than that seen in RBCs from donors with Hb AA.     

Role of the hemobiologist in the detection and prevention of post-transfusional hepatitis

To prevent post-transfusional hepatitis B and C, two epidemiologic studies were performed. The first, based on the frequencies distribution of hepatitis B virus serological markers versus sex and classes of age, has permitted the assessment of the profile of the infection in a population composed of 573 north vietnamese blood donors. There is no significant difference between men and women frequencies of HBs antigen (11.5%), anti-HBs antibody (70.2%) and anti-HBc antibody alone (3.8%), but a significant difference of no-marker frequencies: 7.8% and 17.9% in men and women respectively (X2 = 9.11; p = 0.010). The percentage of no-marker decreases when the mean age of each class increases. The second, using the increase of the serum alanine aminotransferase (ALAT) activity as an indirect marker of non-A, non-B hepatitis for determining in a population of more than 25,000 parisian blood donors, the percentage of donors eliminated. They are between 0.70 and 0.76 in women and 2.26 and 2.46 in men. These investigations can be applied to prevent the hepatitis B transmission in a population of 102 south vietnamese women in age to procreate or to determine the percentage of blood donors eliminated (3.12%) in a population of 2,950 Parisians composed in majority (50.9%) of new donors. The hemobiologist will have an important role to elaborate strategies for orientation of blood gifts with hepatitis B and C virus markers.     

Prevalence of transfusion associated infections in multitransfused children in relation to mandatory screening of HIV in donated blood

Any change in risk behavior related to acquisition of human immunodeficiency virus (HIV) infection is likely to reduce simultaneously the risk for other agents transmitted through identical routes. A study carried out in the city of Delhi, India on the load of transfusion associated infections among multitransfused (MT) children in relation to mandatory screening of HIV infection in donated blood indicated unchanged prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV) infections among the group of MT children transfused after the implementation of mandatory screening of HIV infections in blood banks, i.e. post-implementation period (prevalence of HBV, HCV and HDV being 32.8%, 31.3% and 1.6% respectively) compared to a group of MT children transfused over a similar duration before the implementation of mandatory screening i.e. pre-implementation period (prevalence of HBV, HCV and HDV being 28.1%, 26.6% and 1.6% respectively). However, reduction could be recorded in the prevalence of IgM and IgG classes of antibodies to both CMV and HSV-2 infections among MT children receiving transfusion during the post-implementation period (prevalence of 3.1% and 37.1% for CMV IgM and CMV IgG respectively; prevalence of 3.1% and 25% for HSV-2 IgM and HSV-2 IgG, respectively) compared to the group of MT children transfused in the pre-implementation period (prevalence of 15.6% and 56.3% for CMV IgM and CMV IgG respectively; prevalence of 18.8% and 45.2% for HSV-2 IgM and HSV-2 IgG, respectively). These reductions were statistically significant (p values < 0.02 and < 0.05 for CMV IgM and CMV IgG; p values < 0.01 and < 0.02 for HSV-2 IgM and HSV-2 IgG respectively). These observations were in accordance with the recorded reduction in the prevalence of CMV and HSV-2 infections and unaltered prevalence of HBV, HCV and HDV infections in the group of donors donating blood during the post-implementation period compared to those donating in the pre-implementation period. Study of epidemiological risk factors among blood donors showed a change in behavior towards safer sex practice with only 13.0% of donors in the post-implementation period having history of sex with one or more female commercial sex workers during their donation periods compared to 41.5% of donors in the pre-implementation period having similar history (p < 0.001). However no change could be recorded in the proportion of donors donating at frequency higher than the permissible guidelines among the two groups. The present study points out nosocomial transmission as well as limitations in the existing guidelines for screening of infectious agents in blood banks as possible incriminating factors towards acquisition of hepatitis virus infections in blood donors as well as in MT children.     

Effect of nitric oxide donors on neutrophil responses induced by immune complexes

The present study characterizes the effect of two nitric oxide (NO) donors, S-nitrosoglutathione (GSNO) and sodium nitroprusside (SNP), on the ability of neutrophils to perform different responses triggered by immune complexes (IC). Pretreatment of neutrophils with either GSNO or SNP exerted a biphasic action on antibody-dependent cellular cytotoxicity (ADCC) performed against erythrocytes (E) coated with IgG antibodies (IgG-E), depending on the amount of IgG employed. While with high amounts of antibodies ADCC was markedly inhibited, at low amounts of antibodies it was significantly increased. Both effects were prevented by haemoglobin, a NO scavenger. Moreover, these effects were reproduced by the cell-permeable analogue of cGMP, dibutyryl cGMP (Bt2cGMP). Other neutrophil functions triggered by IgG-E were also examined. It was found that NO donors did not affect either the phagocytosis of IgG-E or the emission of chemiluminescence (CL). Finally, neutrophil functions triggered by soluble IC (sIC) and precipitating IC (pIC) were analysed. It was observed that NO donors did not modify either cytotoxicity performed towards non-sensitized target cells or CL emission. The significance of these results is discussed.     

Uncommon Gm phenotypes in sera from neuroblastoma patients

Gm phenotypes and IgG subclass levels were determined in the sera of 68 patients with neuroblastoma. The frequency of the uncommon phenotypes Gm(a+,f+,g-,b+) and Gm(a+,f+,g+,b-) was found to be significantly higher in the neuroblastoma group than in normal blood donors (p less than 0.001). IgG subclass concentrations in the nine sera with uncommon Gm phenotypes and in the sera of neuroblastoma patients were inconspicuous.     

Opsonization of Actinobacillus actinomycetemcomitans by immunoglobulin G antibodies to the O polysaccharide of lipopolysaccharide

Sera of localized juvenile periodontitis (LJP) patients colonized by Actinobacillus actinomycetemcomitans serotype b often contain markedly elevated levels of immunoglobulin G (IgG) antibodies to serospecific determinants in the O polysaccharide of lipopolysaccharide (LPS), as well as to outer membrane proteins of this species. IgG antibodies in LJP sera are known to opsonize A. actinomycetemcomitans for subsequent phagocytosis and killing by human neutrophils. The objective of this study was to determine whether outer membrane proteins or serospecific determinants in LPS are the primary target for opsonic IgG antibodies in LJP sera. An A. actinomycetemcomitans serotype b O-polysaccharide affinity column was constructed and subsequently used to purify LPS-specific IgG antibodies from LJP serum. The affinity-purified anti-LPS IgG antibodies were enriched in content of IgG2 (66.2%, compared with 37.0% in the total IgG fraction) and were immunospecific for A. actinomycetemcomitans serotype b LPS. In an opsonophagocytic assay using neutrophils from donors who were homozygous for the H131 allotype of Fcy receptor IIa (CD32), it was found that LPS-specific IgG antibodies exhibited substantially greater opsonic activity toward A. actinomycetemcomitans serotype b than an LJP IgG fraction that was depleted of LPS-reactive antibodies but contained antibodies against outer membrane proteins of this species. The results of this study indicate that serospecific determinants in the O polysaccharide of A. actinomycetemcomitans serotype b are a principal target for opsonic antibodies in sera of LJP subjects.     

The AIDS epidemic and commercial plasmapheresis

In 1986 an epidemic of HIV infection among paid plasma donors was identified in Mexico; paid donors were iatrogenically infected in a plasmapheresis center. These paid donors sold both plasma and blood: they provided one-third of blood consumed in 1986. This led to infection of blood recipients, mainly women of childbearing age. Blood transfusion is the leading cause of AIDS in women in Mexico. The male:female ratio decreased from 30:1 in 1986 to 5:1 1990; that coincided with the increase of transfusion-associated AIDS cases. Mexico prohibited the blood trade in 1987, ending the epidemic in paid donors and recipients. latrogenic infection of paid donors in plasmapheresis facilities could help to explain the explosive AIDS epidemic in central Africa and Haiti in the 1980s. There is a temporal and geographical coincidence in the early eighties between that AIDS epidemic, high numbers of hepatitis B asymptomatic carriers and an increased production of serum inactivated hepatitis B vaccine. Plasmapheresis facilities in these developing countries may have taken advantage of the high prevalence of hepatitis B asymptomatic carriers in their populations to obtain plasma for exportation through brokers to developed countries where the vaccine and other plasma products were manufactured. This hypothesis is relevant to establishing preventive policies and warrants further investigation.