Vox Sanguinis

Background and Objectives There is still uncertainty over how the agent of variant Creutzfeld‐Jakob disease (vCJD) would partition during the manufacture of plasma derivatives. In this study, a BSE‐derived agent was used as a vCJD model to determine the extent to which infectivity could be removed by selected steps used in the manufacture of intravenous immunoglobulin (IVIG).

Materials and Methods Murine‐passaged BSE (strain 301V), in the form of a microsomal fraction prepared from infected brain, was used to ‘spike’ the starting material in three experiments. The partitioning of BSE infectivity was measured over Fraction I+III precipitation, borosilicate microfibre depth filtration and Seitz depth filtration, with these steps being examined individually and in series.

Results Most 301V infectivity partitioned into Fraction I+III (log reduction 2·1). Infectivity remaining in Supernatant I+III was reduced by AP20 glass‐fibre depth filtration (log reduction 0·6) and subsequently removed to below the limit of detection by Seitz KS80 depth filtration, giving an overall log reduction of ≥ 2·9 for the three steps in series. By contrast, glass‐fibre depth filtration gave a log reduction of 2·4 when challenged directly with ‘spiked’ feedstock. Seitz KS80 depth filtration gave a log reduction of ≥ 3·1 when challenged directly with ‘spiked’ feedstock and also removed residual infectivity to below the limit of detection when applied as the final step in series.

Conclusions Results using a BSE‐derived agent suggest that vCJD infectivity should be substantially removed from immunoglobulin G (IgG) solutions by Fraction I+III precipitation and Seitz KS80 depth filtration. The three different process steps examined acted in a complementary manner to one another when operated in series. However, the data demonstrated that it would be inappropriate to add together the reduction factors that had been derived for each step in isolation.

Human antibodies can be generated by recombinant technology. The human immunoglobulin repertoire can be tapped in an effective manner by the so called V gene phage display technology. Using this technique the genes encoding the variable domains of an antibody of interest can be captured from the B cell repertoire. With these V genes tailor‐made immune recognition molecules can be obtained by a ‘design and build’ strategy. These novel developments will lead to the introduction of a manifold of antibody based therapies into the clinic in coming decades. Recombinant antibody technology also provides unique opportunities to study the molecular structure of antibody variable domains against blood cell antigens. Such studies might possibly lead to the development of new therapies for antibody mediated blood cell destruction.

Abstract. In a randomized, controlled double‐blind study, 15 patients with AIDS‐related complex/Walter‐Reed 5 (ARC/WR5) were compared during 6 months intravenous immunoglobulin (IVIG) treatment (0.4 g/kg body weight every 2 weeks) with 15 placebo‐treated patients. This study was aimed at the lymphocyte response to T and B cell mitogens and antigens. ³H‐thymidine uptake was determined after stimulation with the unspecific mitogens phytohemagglutinin (PHA), pokeweed mitogen (PWM), formalinized Staphylococcus aureus‐Cowan I (SAC), and with the antigens tuberculin and herpes simplex virus (HSV) at the onset, on days 85, 183, 267 and 351; IgG and IgM antibodies against HSV were measured by ELISA. In addition, 30 untreated HIV‐negative controls were tested. For the T cell mitogen PHA, T‐cell‐dependent B cell mitogen PWM and B cell mitogen SAC, no differences between the two patient groups were observed before therapy nor in the course of therapy or the 6‐month observation period thereafter. The entire patient group showed significantly impaired mitogenic response on day 1 as compared to the controls. There was no significant difference in response to tuberculin between the patients and HIV‐negative controls, nor for both patients groups before and in the course of treatment. All patients had IgG antibodies against HSV. Three of them showed blastogenic lymphocyte response to HSV on day 1. Among 19 seropositive controls, 7 individuals showed positive HSV lymphocyte response; but for both patient groups, there was no significant difference before and in the course of the treatment and observation period. We concluded that, in spite of some clinical improvement regarding fever and fatigue during IVIG treatment of ARC/WR5 patients, there is no influence on lymphocyte function, as measured by response to mitogens and antigens.

Summary. Cold auto‐antibodies reacting with an antigen that appears to be independent of the Ii system are described. No human blood sample lacking the reacting antigen (designated Sp₁) could be found but the common serological behaviour suggests that the antisera form a homogeneous group. The evidence suggests that these antibodies may be directed against a basic species antigen common to all human cells.

Abstract. We have evaluated the western blot (WB) test for distinguishing anti‐HTLV III ELISA‐positive donors who have likely been exposed to HTLV III from those that are false positives. Of 1,955 donors, 26 were positive for anti‐HTLV III by ELISA testing. Only 6 (23%) were positive by WB: 5 of these 6 were male homosexuals with multiple partners and 5 of 6 had low Th/Ts ratios. The WB‐positive donors gave the highest absorbance values in the anti‐HTLV III ELISA assay. The immunologic abnormalities in the WB‐positive donors suggest that they should be notified of their test results. We conclude that basing a donor notification policy on WB results is the optimum public health strategy for blood banks at the present time.

Abstract. The present knowledge on chemical, enzymatic, serologic and genetic aspects of ABH antigens is reviewed in an effort to produce a simple and coherent genetic model for the biosynthesis of these antigens and chemically related structures. The genetic control of type 1 (Le^a, Le^b, Le^c and Le^d), type 2 (X, Y, I, and H), type 3 and type 4 ABH and related antigens in different animal and human tissues is analyzed, taking into account the properties of the glycosyltransferases which are involved in their synthesis and considering possible competition for common acceptor and donor substrates. The phylogeny of ABH determinants shows that they appeared as tissular antigens much earlier than as red cell antigens. The ontogeny of ABH antigens suggests that they behave as differentiation antigens, and an effort is made to correlate their tissular distribution in the adult with the embryological origin of each tissue.